TREATMENT OF A CANCER BY MICROBIOME MODULATION

Description

INTRODUCTION

Mammals are colonized by microbes in the gastrointestinal (GI) tract, on the skin, and in other epithelial and tissue niches such as the oral cavity, eye surface and vagina. The gastrointestinal tract harbors an abundant and diverse microbial community. Hundreds of different species may form a commensal community in the GI tract of a healthy person. Interactions between microbial strains in these populations and between microbes and the host, e.g., the host immune system, shape the community structure, with availability of and competition for resources affecting the distribution of microbes. Such resources may be food, location and the availability of space to grow or a physical structure to which the microbe may attach. For example, host diet is involved in shaping the GI tract flora.

Harnessing the host immune system by microbiome modulation constitutes a promising approach for the treatment of cancer because of its potential to specifically target tumor cells while limiting harm to normal tissue, with durability of benefit associated with immunologic memory. Enthusiasm for this approach has been fueled by recent clinical success, particularly with antibodies that block immune inhibitory pathways, for example the CTLA-4 and the PD-1/PD-L1 pathways (Hodi et al. New Engl J Med 363:711-723 (2010); Hamid et al. New Engl J Med 369:134-144 (2013); herein incorporated by reference in their entireties). Early data have indicated that clinical responses to these immunotherapies are more frequent in patients who show evidence of an endogenous T cell response ongoing in the tumor microenvironment at baseline (Tumeh et al. Nature 51:568-571 (2014); Spranger et al. Sci Transl Med 5:200ra116 (2013); Ji et al. Cancer Immunol Immunother: CII 61, 1019-1031 (2012); Gajewski et al. Cancer J 16:399-403 (2010); herein incorporated by reference in their entireties). However, many cancer therapeutics have limited efficacy and there is a need to extend the range of patients who can benefit from these treatments. A number of factors can influence the efficacy of a cancer treatment, for example, smoking history, diabetes, obesity, and tumor size. It has been suggested that the microbiome of an individual can be a factor influencing efficacy.

Fecal transplantation and some individual species have been proposed as treatments for patients suffering from certain cancers either as sole treatments or as adjunctive therapy with other cancer treatments. Fecal transplantation, however, is generally a procedure of last resort because of, for example, the difficulty in producing a consistent product, the potential to transmit infectious or allergenic agents between hosts, and variability between fecal donors. There is a need for improved methods of selecting fecal donors and/or defined microbiome compositions that can be used to effect anti-tumor activity, alone or in combination with other cancer treatment methods, e.g., checkpoint inhibitors.

SUMMARY

In one aspect, methods are provided for identifying donors of fecal matter that can improve a subject's response to an immune checkpoint inhibitor comprising determining whether the microbiome of the potential donor comprises bacteria belonging to one or more species that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii, i.e., they belong to the family Ruminococcaceae as defined herein.

In another aspect, methods are provided for identifying donors of fecal matter that can improve a subject's response to a checkpoint inhibitor comprising determining whether the microbiome of the potential donor comprises bacteria belonging to one or more species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.

In another aspect, methods are provided for identifying donors of fecal matter that can improve a subject's response to a checkpoint inhibitor comprising determining whether the microbiome of the potential donor comprises one or more strain of bacteria belonging to one or more of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135 as defined herein.

In some aspects, fecal material from identified donors can be used, e.g., in fecal microbiome transplantation or in a processed form derived from such material, for example a preparation enriched in Firmicutes (e.g., Clostridia, Clostridiales, or spore formers), that are in vegetative and/or spore form.

In another aspect, therapeutic compositions are provided that are derived from fecal matter obtained from a donor identified using a method described herein.

In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition derived from fecal matter obtained from a donor identified using a method described herein.

In another aspect, methods are provided for identifying donated fecal matter that can improve a subject's response to a checkpoint inhibitor comprising determining whether the donated fecal matter comprises bacteria belonging to one or more species that are phylogenetic descendants of the MRCA of Faecalibacterium prausnitzii and Flavonifractor plautii.

In another aspect, methods are provided for identifying donated fecal matter that can improve a subject's response to a checkpoint inhibitor comprising determining whether the microbiome of the potential donor comprises bacteria belonging to one or more species that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the one or more species may have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.

In another aspect, methods are provided for identifying donated fecal matter that can improve a subject's response to a checkpoint inhibitor comprising determining whether the donated fecal matter comprises bacteria belonging to one or more species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.

In another aspect, methods are provided for identifying donated fecal matter that can improve a subject's response to a checkpoint inhibitor comprising determining whether the donated fecal matter comprises one or more strain of bacteria belonging to one or more of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135 as defined herein.

In some aspects, fecal material from identified donated fecal matter can be used, e.g., in fecal microbiome transplantation or in a processed form derived from such material, for example a preparation enriched in Firmicutes (e.g., Clostridia, Clostridiales, or spore formers), that are in vegetative and/or spore form.

In another aspect, therapeutic compositions are provided that are derived from donated fecal matter identified using a method described herein.

In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition derived from donated fecal matter identified using a method described herein.

In one aspect, provided are therapeutic compositions comprising an effective amount of an isolated population of bacteria belonging to one or more of the family Ruminococcaceae, e.g., the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof. In some embodiments, the therapeutic composition may comprise bacteria belonging to at least two, three or four of the genera listed.

In another aspect, provided are therapeutic compositions comprising an effective amount of an isolated population of bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii. In another aspect, provided are therapeutic compositions comprising an effective amount of an isolated population of bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the therapeutic compositions may comprise one or more bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.

In some embodiments, the therapeutic composition may comprise at least two, three, four, five or more of the species listed. In another aspect, provided are therapeutic compositions comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In another aspect, provided are therapeutic compositions comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof. In another aspect, provided are therapeutic compositions comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In some embodiments, the therapeutic composition may comprise bacteria belonging to at least two, three, four, five or more of the genera listed.

In another aspect, provided are therapeutic compositions comprising an effective amount of an isolated population of bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, provided are therapeutic compositions comprising an effective amount of an isolated population of bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, provided are therapeutic compositions comprising an effective amount of an isolated population of bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof. In some embodiments, the therapeutic composition may comprise at least two, three, four, five or more of the species listed.

In one aspect, provided are therapeutic compositions comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof. In some embodiments, the therapeutic composition may comprise bacteria belonging to at least two, three or four the genera listed.

In another aspect, provided are therapeutic compositions comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Bamesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In another aspect, provided are therapeutic compositions comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof. In another aspect, provided are therapeutic compositions comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Bamesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In some embodiments, the therapeutic composition may comprise bacteria belonging to at least two, three, four, five or more of the genera listed.

In another aspect, provided are therapeutic compositions comprising an effective amount of a purified population of bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, provided are therapeutic compositions comprising an effective amount of a purified population of bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, provided are therapeutic compositions comprising an effective amount of a purified population of bacteria species selected from Bamesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof. In some embodiments, the therapeutic composition may comprise at least two, three, four, five or more of the species listed.

In some embodiments, the therapeutic compositions further comprise an anticancer agent. In some embodiments, the anticancer agent is a checkpoint inhibitor. In some embodiments, the checkpoint inhibitor is selected from an anti-PD-1 antibody, an anti-CTLA-4 antibody, an anti-PD-L1 antibody or combinations thereof. In some embodiments, the checkpoint inhibitor is selected from pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, ipilimumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, BMS-936558, MK-3475, CT 011, MPDL3280A, MEDI-4736, MSB-0020718C, AUR-012, LAG-3, OX40 inhibitors, OX40L inhibitors, TIGIT inhibitors, STI-A1010 or combinations thereof. In some embodiments, the anticancer agent is cyclophosphamide.

In some embodiments, each isolated population of bacteria in the therapeutic composition is present in the composition at a concentration of at least about 1×10²viable colony forming units. In some embodiments, each isolated population of bacteria in the therapeutic composition is present in the composition at a concentration of about 1×10²to 1×10⁹viable colony forming units.

In some embodiments, a fraction of the isolated population of bacteria in the therapeutic composition comprises a spore-forming bacteria. In some embodiments, a fraction of the isolated population of bacteria in the therapeutic composition is in spore form.

In some embodiments, the therapeutic compositions further comprise a pharmaceutically acceptable excipient. In some embodiments, the therapeutic compositions are formulated for delivery to the intestine. In some embodiments, the therapeutic compositions are enterically coated. In some embodiments, the therapeutic compositions are formulated for oral administration. In some embodiments, the therapeutic compositions are formulated into a food or beverage.

In some embodiments the therapeutic compositions can reduce the rate of tumor growth in an animal model.

In one aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof. In some embodiments of the methods, the therapeutic composition may comprise bacteria belonging to at least two, three or four the genera listed.

In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria that are phylogenetic descendants of the MRCA of Faecalibacterium prausnitzii and Flavonifractor plautii. In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the therapeutic compositions may comprise one or more bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.

In some embodiments, the therapeutic composition may comprise at least two, three, four, five or more of the species listed.

In some embodiments, the composition is formulated for multiple administrations. In some embodiments, the composition is formulated for at least 1, 2, 3, 4, 5, 6, 7, or 8 administrations.

In some embodiments, the purified population of bacteria comprises bacteria from at least two genera or species, and wherein the ratio of the two bacteria is 1:1. In some embodiments, the purified population of bacteria comprises bacteria from at least, at most, or exactly 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 20, 30, 40, or 50 (or any derivable range therein) different families, genera, or species of bacteria. In some embodiments, the ratio of one family, genera, or species of bacteria to another family, genera, or species of bacteria present in the composition is at least, at most, or exactly 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, 1:50, 1:55, 1:60, 1:65, 1:70, 1:75, 1:80, 1:85, 1:90, 1:95, 1:100, 1:150, 1:200, 1:250, 1:300, 1:350, 1:400, 1:450, 1:500, 1:600, 1:700, 1:800, 1:900, 1:1000, 1:1500, 1:2000, 1:2500, 1:3000, 1:3500, 1:4000, 1:4500, 1:5000, 1:1550, 1:6000, 1:6500, 1:7000, 1:7500, 1:8000, 1:8500, 1:9000, 1:9500, 1:10000, 1:1200, 1:14000, 1:16000, 1:18000, 1:20000, 1:30000, 1:40000, 1:50000, 1:60000, 1:70000, 1:80000, 1:90000, or 1:100000 (or any derivable range therein).

The compositions of the disclosure may exclude one or more bacteria genera or species described herein or may include less than 1×10⁶, 1×10⁵, 1×10⁴, 1×10³, or 1×10²cells or viable CFU (or any derivable range therein) of one or more of the bacteria described herein.

In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof. In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Bamesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In some embodiments of the methods, the therapeutic composition may comprise bacteria belonging to at least two, three, four, five or more of the genera listed.

In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Bamesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof. In some embodiments of the methods, the therapeutic composition may comprise at least two, three, four, five or more of the species listed.

In one aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof. In some embodiments of the methods, the therapeutic composition may comprise bacteria belonging to at least two, three or four the genera listed.

In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Bamesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof. In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Bamesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In some embodiments of the methods, the therapeutic composition may comprise bacteria belonging to at least two, three, four, five or more of the genera listed.

In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, methods of treating a cancer in a mammalian subject are provided comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Bamesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof. In some embodiments of the methods, the therapeutic composition may comprise at least two, three, four, five or more of the species listed.

In some embodiments, the therapeutic compositions used in the methods of treating cancer further comprise an anticancer agent. In some embodiments, the anticancer agent is a checkpoint inhibitor. In some embodiments, the checkpoint inhibitor is selected from an anti-PD-1 antibody, an anti-CTLA-4 antibody, an anti-PD-L1 antibody or combinations thereof. In some embodiments, the checkpoint inhibitor is selected from pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, ipilimumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, BMS-936558, MK-3475, CT 011, MPDL3280A, MEDI-4736, MSB-0020718C, AUR-012, LAG-3, OX40 inhibitors, OX40L inhibitors, TIGIT inhibitors, STI-A1010 or combinations thereof. In some embodiments, the anticancer agent is cyclophosphamide.

In some embodiments of the methods, each isolated population of bacteria in the therapeutic composition is present in the composition at a concentration of at least about 1×10²viable colony forming units. In some embodiments of the methods, each isolated population of bacteria in the therapeutic composition is present in the composition at a concentration of about 1×10²to 1×10⁹viable colony forming units.

In some embodiments of the methods, a fraction of the isolated population of bacteria in the therapeutic composition comprises a spore-forming bacteria. In some embodiments of the methods, a fraction of the isolated population of bacteria in the therapeutic composition is in spore form.

In some embodiments of the methods, the therapeutic compositions further comprise a pharmaceutically acceptable excipient. In some embodiments of the methods, the therapeutic compositions are formulated for delivery to the intestine. In some embodiments of the methods, the therapeutic compositions are enterically coated. In some embodiments, the therapeutic compositions are formulated for oral administration. In some embodiments of the methods, the therapeutic compositions are formulated into a food or beverage.

In some embodiments of the methods, the mammalian subject is a human.

In some embodiments of the methods, the cancer is selected from metastatic melanoma, melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, Merkel cell skin cancer (Merkel cell carcinoma), or Hodgkin lymphoma.

In some embodiments of the methods, prior to administration of the isolated population of bacteria, the subject is subjected to antibiotic treatment and/or a bowel cleanse.

In one aspect, methods of identifying if a mammalian subject is a candidate for anticancer treatment are provided, the method comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence of the genera of bacteria in the microbiome sample, and c) determining that the subject is a candidate for anticancer treatment if the microbiome sample comprises bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof.

In another aspect, methods of identifying a mammalian subject as a candidate for anticancer treatment are provided, the method comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the subject is a candidate for anticancer treatment if the microbiome sample comprises bacteria belonging to one or more species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.

In another aspect, methods of identifying a mammalian subject as a candidate for anticancer treatment are provided, the method comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence and/or abundance of the genera of bacteria in the microbiome sample, and c) determining that the subject is a candidate for anticancer treatment if the microbiome sample comprises one or more of the genera Bamesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In another aspect, methods of identifying a mammalian subject as a candidate for anticancer treatment are provided, the method comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the subject is a candidate for anticancer treatment if the microbiome sample comprises bacteria species selected from Alistipes senegalensis, Bamesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, methods of identifying a mammalian subject as a candidate for anticancer treatment are provided, the method comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the subject is a candidate for anticancer treatment if the microbiome sample comprises bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, methods of identifying a mammalian subject as a candidate for anticancer treatment are provided, the method comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the subject is a candidate for anticancer treatment if the microbiome sample comprises bacteria species selected from Bamesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof. In methods in which a microbiome sample is obtained, in some cases the microbiome sample is obtained from a fecal sample. In some cases, the microbiome sample is obtained by mucosal biopsy.

In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii. In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof. In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof. In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising one or more of the genera Bamesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof. In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In another aspect, provided herein are methods of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof.

In another aspect, provided herein are methods comprising evaluating a microbiome profile for bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii in a sample from a subject. In another aspect, provided herein are methods comprising evaluating a microbiome profile for bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae in a sample from a subject. In some embodiments, the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In another aspect, provided herein are methods comprising evaluating a microbiome profile for bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof in a sample from the subject. In another aspect, provided herein are methods comprising evaluating a microbiome profile for bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof in a sample from a subject. In another aspect, provided herein are methods comprising evaluating a microbiome profile for bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof in a sample from a subject. In another aspect, provided herein are methods comprising evaluating a microbiome profile for one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof in a sample from a subject. In another aspect, provided herein are methods comprising evaluating a microbiome profile for bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof in a sample from a subject. In another aspect is a method comprising evaluating a microbiome profile for bacteria species selected from Alistipes senegalensis, Bamesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof in a sample from a subject. In another aspect is a method comprising evaluating a microbiome profile for bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof in a sample from a subject. In another aspect, provided herein are methods comprising evaluating a microbiome profile for bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof in a sample from a subject.

In some embodiments, the method further comprises comparing the microbiome profile to a control microbiome. In some embodiments, the control microbiome comprises a microbiome sample from a subject determined to be a responder to an anticancer treatment. In some embodiments, the control microbiome comprises a microbiome sample from a subject determined to be a non-responder to an anticancer treatment.

In some embodiments of the methods of identifying a mammalian subject as a candidate for anticancer treatment, the subject is determined to be a candidate for checkpoint inhibitor anticancer treatment. In some embodiments of the methods of identifying a mammalian subject as a candidate for anticancer treatment, the subject is determined to be a candidate for cyclophosphamide anticancer treatment.

In some embodiments of the methods of identifying a mammalian subject as a candidate for anticancer treatment, the mammalian subject is a human.

In some embodiments of the methods of identifying a mammalian subject as a candidate for anticancer treatment, the cancer is selected from metastatic melanoma, melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, Merkel cell skin cancer (Merkel cell carcinoma), or Hodgkin lymphoma.

In some embodiments, the subject has previously been treated for the cancer. In some embodiments, the subject has been determined to be a non-responder to the previous treatment. In some embodiments, the subject has been determined to have a have a toxic response to the previous treatment. In some embodiments, the previous treatment comprises immune checkpoint blockade monotherapy or combination therapy. In some embodiments, the cancer is recurrent cancer. In some embodiments, the subject has not received a prior anticancer therapy.

In one aspect, therapeutic compositions are provided comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium and Subdoligranulum.

In another aspect, therapeutic compositions are provided comprising an effective amount of an isolated population of bacteria belonging to one or more species that are phylogenetic descendants of the MRCA of Faecalibacterium prausnitzii and Flavonifractor plautii. In another aspect, therapeutic compositions are provided comprising an effective amount of an isolated population of bacteria belonging to one or more species that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the one or more species may have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In another aspect, therapeutic compositions are provided comprising an effective amount of an isolated population of bacteria belonging to one or more species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.

In another aspect, therapeutic compositions are provided comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Bamesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter and Parabacteroides. In another aspect, therapeutic compositions are provided comprising an effective amount of an isolated population of bacteria belonging one or more of to the genera Bamesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter and Parabacteroides.

In another aspect, therapeutic compositions are provided comprising an effective amount of an isolated population of bacteria species Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme and Parabacteroides distasonis. In another aspect, therapeutic compositions are provided comprising an effective amount of an isolated population of bacteria species Bamesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus and Parabacteroides distasonis.

In one aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Tables 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10 or 11. In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Tables 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10 or 11. In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to three or more of the species listed in Tables 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10 or 11. In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to four or more of the species listed in Tables 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10 or 11.

In one aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Table 1A. In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Table 1B. In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Table 10. In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Table 11.

In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Table 1A. In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Table 1B. In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Table 10. In another aspect, therapeutic compositions are provided comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Table 11.

It is specifically contemplated that any limitation discussed with respect to one embodiment of the invention may apply to any other embodiment of the invention. Furthermore, any composition of the invention may be used in any method of the invention, and any method of the invention may be used to produce or to utilize any composition of the invention. Aspects of an embodiment set forth in the Examples are also embodiments that may be implemented in the context of embodiments discussed elsewhere in a different Example or elsewhere in the application, such as in the Summary of Invention, Detailed Description of the Embodiments, Claims, and description of Figure Legends.

Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

FIG. 1. 16S Alpha Diversity. The figure is a plot showing Observed, Shannon, and Inverse Simpson 16S alpha diversity scores of the microbiome in responder and non-responder patients. Error bars represent the distribution of scores. Responders (left bar within each panel); non-responders (1 bar within each panel). Where outliers are present, they are shown as individual points—otherwise, boxes extend from the first to third quartiles of the data, with whiskers extending the length of the data. Outliers are defined as points which lie outside of the first quartile minus 1.5*IQR (“interquartile range”, e.g. the distance between the first to third quartiles), or the third quartile plus 1.5*IQR.

FIG. 2. Prevalence Analysis. The figure is a volcano plot of differential 16S rDNA prevalence results. Significantly differentially prevalent OTUs/genera are marked with a rectangular label (p-value <=0.10, Fisher's exact test).

FIG. 3 is a plot showing Bray-Curtis Beta Diversity. Approximately 200 samples from healthy donors collected by the Human Microbiome Project (HMP) were used to generate a set of background samples to compare to the collected WMS data. Bray-Curtis dissimilarity across the WMS and HMP data was represented in a multidimensional scaling (MDS) format, and Linear Discriminant Analysis (LDA) was used to generate a classification line to separate responder and non-responder samples.

FIG. 4 is a plot showing the Species Data overlaid on Bray-Curtis Beta Diversity. Individual species data from the samples were mapped onto the MDS plot of FIG. 3. Circled species are all members of the family Ruminococcaceae and these data demonstrate that Ruminococcaceae are associated with responders.

FIG. 5 is a graph showing how the relative abundance of Bacteroidia are associated with response to checkpoint therapy. Samples are ordered by decreasing relative abundance. Data from responder samples are shown in gray while non-responders are shown in black. The cut-off (dashed line) maximizes sensitivity while maintaining 100% specificity.

FIG. 6 is a phylogenetic tree of Ruminococcaceae derived from 16S rDNA sequences demonstrating that a clade-based definition of Ruminococcaceae more accurately represents phylogenetic relationships. Taxa classified as Ruminococcaceae in NCBI are in black; taxa in other families are underlined. NCBI-based classification is clearly not consistent with phylogeny. Here, a definition of Ruminococcaceae based on an internal clade system (clades 14, 61, 101, 125, and 131) is consistent with phylogeny. Clade 13 was excluded as it is highly divergent from the remaining Ruminococcaceae.

FIG. 7 is a graph showing that clade-based relative abundance of Ruminococcaceae is associated with response to checkpoint therapy. Samples are ordered by decreasing relative abundance. Responders are shown in gray while non-responders are shown in black. The threshold was increased from 9.5% with the NCBI-based definition of Ruminococcaceae to 12% with the clade-based definition, as a greater number of Ruminococcaceae species were detected by the latter, resulting in higher per sample abundances. The threshold was chosen to maximize sensitivity while maintaining 100% specificity.

FIG. 8 is a plot showing the distribution of Ruminococcaceae clade-based abundance with Bacteroidia clade-based abundance. Eighty percent of responders fall outside of lower left quadrant.

FIG. 9 is a plot of a receiver operating characteristic (ROC) curve for Ruminococcaceae clade-based relative abundance in combined dataset (n=112) as a predictor of response to checkpoint therapy.

FIG. 10 is a plot of a distribution of Ruminococcaceae clade-based abundance in the combined dataset (n=112). Seventy-two percent of total non-responders lie to the left of the dotted line (<12% Ruminococcaceae), while 68% of total responders lie to right of the line (>=12% Ruminococcaceae). Bacteroidia relative abundance is plotted to allow visual separation of samples.

FIG. 11 is a plot of a ROC curve for Ruminococcaceae clade-based relative abundance in combined dataset excluding stable disease patients (n=85) as a predictor of response to checkpoint therapy.

DETAILED DESCRIPTION
I. Definitions

As used herein, the terms “or” and “and/or” are utilized to describe multiple components in combination or exclusive of one another. For example, “x, y, and/or z” can refer to “x” alone, “y” alone, “z” alone, “x, y, and z,” “(x and y) or z,” “x or (y and z),” or “x or y or z.” Is is specifically contemplated that x, y, or z may be specifically excluded from an embodiment.

Throughout this application, the term “about” is used according to its plain and ordinary meaning in the area of cell biology to indicate that a value includes the standard deviation of error for the device or method being employed to determine the value.

The term “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. The phrase “consisting of” excludes any element, step, or ingredient not specified. The phrase “consisting essentially of” limits the scope of described subject matter to the specified materials or steps and those that do not materially affect its basic and novel characteristics. It is contemplated that embodiments described in the context of the term “comprising” may also be implemented in to context of the term “consisting of” or “consisting essentially of.” “Microbiome” refers to the communities of microbes that live in or on an individual's body, both sustainably and transiently, including eukaryotes, archaea, bacteria, and viruses (including bacterial viruses (i.e., phage)).

“Dysbiosis” refers to a state of the microbiota or microbiome of the GI tract or other body area, including mucosal or skin surfaces in which the normal diversity and/or function of the ecological network is disrupted. Any disruption from the preferred (e.g., ideal) state of the microbiota can be considered a dysbiosis, even if such dysbiosis does not result in a detectable decrease in health. This state of dysbiosis may be unhealthy, it may be unhealthy under only certain conditions, or it may prevent a subject from becoming healthier. Dysbiosis may be due to a decrease in diversity, the overgrowth of one or more pathogens or pathobionts, symbiotic organisms able to cause disease only when certain genetic and/or environmental conditions are present in a patient, or the shift to an ecological network that no longer provides a beneficial function to the host and therefore no longer promotes health.

A “spore” or a population of “spores” includes bacteria (or other single-celled organisms) that are generally viable, more resistant to environmental influences such as heat and bacteriocidal agents than vegetative forms of the same bacteria, and typically are capable of germination and out-growth. “Spore-formers” or bacteria “capable of forming spores” are those bacteria containing the genes and other necessary features to produce spores under suitable environmental conditions.

The terms “pathogen”, “pathobiont” and “pathogenic” in reference to a bacterium or any other organism or entity includes any such organism or entity that is capable of causing or affecting a disease, disorder or condition of a host organism containing the organism or entity.

The term “isolated” encompasses a bacterium or other entity or substance that has been (1) separated from at least some of the components with which it was associated when initially produced (whether in nature or in an experimental setting), and/or (2) produced, prepared, purified, and/or manufactured by the hand of man. Isolated bacteria may be separated from at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or more of the other components with which they were initially associated. In some embodiments, isolated bacteria are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure. As used herein, a substance is “pure” if it is substantially free of other components. The terms “purify,” “purifying” and “purified” refer to a bacterium or other material that has been separated from at least some of the components with which it was associated either when initially produced or generated (e.g., whether in nature or in an experimental setting), or during any time after its initial production. A bacterium or a bacterial population may be considered purified if it is isolated at or after production, such as from a material or environment containing the bacterium or bacterial population, and a purified bacterium or bacterial population may contain other materials up to about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or above about 90% and still be considered “isolated.” In some embodiments, purified bacteria and bacterial populations are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure. In the instance of bacterial compositions provided herein, the one or more bacterial types present in the composition can be independently purified from one or more other bacteria produced and/or present in the material or environment containing the bacterial type. Bacterial compositions and the bacterial components thereof are generally purified from residual habitat products.

“Inhibition” of a pathogen encompasses the inhibition of any desired function or activity of the bacterial compositions of the present invention. Demonstrations of pathogen inhibition, such as decrease in the growth of a pathogenic bacterium or reduction in the level of colonization of a pathogenic bacterium are provided herein and otherwise recognized by one of ordinary skill in the art. Inhibition of a pathogenic bacterium's “growth” may include inhibiting the increase in size of the pathogenic bacterium and/or inhibiting the proliferation (or multiplication) of the pathogenic bacterium. Inhibition of colonization of a pathogenic bacterium may be demonstrated by measuring the amount or burden of a pathogen before and after a treatment. An “inhibition” or the act of “inhibiting” includes the total cessation and partial reduction of one or more activities of a pathogen, such as growth, proliferation, colonization, and function.

The “colonization” of a host organism includes the transitory (e.g., for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 1 week) or non-transitory (e.g., greater than one week, at least two weeks, at least three weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 3 month, at least 4 months, at least 6 months) residence of a bacterium or other microscopic organism. As used herein, “reducing colonization” of a host subject's gastrointestinal tract (or any other microbiotal niche) by a pathogenic bacterium includes a reduction in the residence time of the pathogen in the gastrointestinal tract as well as a reduction in the number (or concentration) of the pathogen in the lumen of the gastrointestinal tract or adhered to the mucosal surface of the gastrointestinal tract. Measuring reductions of adherent pathogens may be demonstrated, e.g., by a biopsy sample, or luminal reductions may be measured indirectly, e.g., indirectly by measuring the pathogenic burden in the stool of a mammalian host.

A “combination” of two or more bacteria includes the physical co-existence of the two bacteria, either in the same material or product or in physically connected products, as well as the temporal co-administration or co-localization of the two bacteria.

A “cytotoxic” activity or bacterium includes the ability to kill another bacterial cell, such as a pathogenic bacterial cell or a closely related species of strain. A “cytostatic” activity or bacterium includes the ability to inhibit, partially or fully, growth, metabolism, and/or proliferation of a bacterial cell, such as a pathogenic bacterial cell.

To be free of “non-comestible products” means that a bacterial composition or other material provided herein does not have a substantial amount of a non-comestible product, e.g., a product or material that is inedible, harmful or otherwise undesired in a product suitable for administration, e.g., oral administration, to a human subject.

“Microbiome” refers to the genetic content of the communities of microbes that live in and on the human body, both sustainably and transiently, including eukaryotes, archaea, bacteria, and viruses (including bacterial viruses (i.e., phage)), wherein “genetic content” includes genomic DNA, RNA such as micro RNA and ribosomal RNA, the epigenome, plasmids, and all other types of genetic information.

“Augmentation” of a type of bacterium, e.g., a species, is an effect of treatment with a composition of the invention that is characterized by post-treatment detection of an increased abundance of a species not present in the composition by a nonparametric test of abundance.

“Engraftment” of a type of bacterium, e.g., a species, is an effect of treatment with a composition of the invention that is characterized by post-treatment detection of a species from the administered composition, which is not detected in the treated subject pretreatment. Methods of detection are known in the art. In one example, the method is PCR detection of a 16S rDNA sequence using standard parameters for PCR.

“Residual habitat products” refers to material derived from the habitat for microbiota within or on a human or animal. For example, microbiota live in feces in the gastrointestinal tract, on the skin itself, in saliva, mucus of the respiratory tract, or secretions of the genitourinary tract (i.e., biological matter associated with the microbial community). Substantially free of residual habitat products means that the bacterial composition no longer contains the biological matter associated with the microbial environment on or in the human or animal subject and is 100% free, 99% free, 98% free, 97% free, 96% free, or 95% free of any contaminating biological matter associated with the microbial community. Residual habitat products can include abiotic materials (including undigested food) or it can include unwanted microorganisms and/or fragments of microorganisms. Substantially free of residual habitat products may also mean that the bacterial composition contains no detectable cells from a human or animal and that only microbial cells are detectable. In one embodiment, substantially free of residual habitat products may also mean that the bacterial composition contains no detectable viral (including bacterial viruses (i.e., phage) or human viruses), fungal, or mycoplasmal contaminants. In another embodiment, it means that fewer than 1×10⁻²%, 1×10⁻³%, 1×10⁻⁴%, 1×10⁻⁶%, 1×10⁻⁶%, 1×10⁻⁷%, 1×10⁻⁸% of the viable cells in the bacterial composition are human or animal, as compared to microbial cells. There are multiple ways to accomplish this degree of purity, none of which are limiting. Thus, contamination may be reduced by isolating desired constituents through multiple steps of streaking to single colonies on solid media until replicate (such as, but not limited to, two) streaks from serial single colonies have shown only a single colony morphology. Alternatively, reduction of contamination can be accomplished by multiple rounds of serial dilutions to single desired cells (e.g., a dilution of 10⁻⁸or 10⁻⁹), such as through multiple 10-fold serial dilutions. This can further be confirmed by showing that multiple isolated colonies have similar cell shapes and Gram staining behavior. Other methods for confirming adequate purity include genetic analysis (e.g. PCR, DNA sequencing), serology and antigen analysis, enzymatic and metabolic analysis, and methods using instrumentation such as flow cytometry with reagents that distinguish desired constituents from contaminants.

“Phylogenetic tree” refers to a graphical representation of the evolutionary relationships of one genetic sequence to another that is generated using a defined set of phylogenetic reconstruction algorithms (e.g. parsimony, maximum likelihood, or Bayesian). Nodes in the tree represent distinct ancestral sequences and the confidence of any node is provided by a bootstrap or Bayesian posterior probability, which measures branch uncertainty.

“Operational taxonomic unit (OTU, plural OTUs)”, in some embodiments, refers to a terminal leaf in a phylogenetic tree and is defined by a specific genetic sequence and all sequences that share sequence identity to this sequence at the level of species. A “type” or a plurality of “types” of bacteria includes an OTU or a plurality of different OTUs, and also encompasses a strain, species, genus, family or order of bacteria. The specific genetic sequence may be the 16S rDNA sequence or a portion of the 16S rDNA sequence or it may be a functionally conserved housekeeping gene found broadly across the eubacterial kingdom. OTUs share at least 95%, 96%, 97%, 98%, or 99% sequence identity. OTUs generally defined by comparing sequences between organisms. Sequences with less than 95% sequence identity are not considered to form part of the same OTU. In some embodiments, metagenomics methods, known in the art, are used to identify species and/or OTUs.

“Clade” refers to the set of OTUs or members of a phylogenetic tree downstream of a statistically valid node in a phylogenetic tree. A clade is a group of related organisms representing all of the phylogenetic descendants of a common ancestor. The clade comprises a set of terminal leaves in the phylogenetic tree that is a distinct monophyletic evolutionary unit.

The terms “subject” or “patient” refers to any animal subject including humans, laboratory animals (e.g., primates, rats, mice), livestock (e.g., cows, sheep, goats, pigs, turkeys, chickens), and household pets (e.g., dogs, cats, rodents, etc.). The subject or patient may be healthy, or may be suffering from an infection due to a gastrointestinal pathogen or may be at risk of developing or transmitting to others an infection due to a gastrointestinal pathogen.

The term “pathobiont” refer to specific bacterial species found in healthy hosts that may trigger immune-mediated pathology and/or disease in response to certain genetic or environmental factors. Chow et al., (2011) Curr Op Immunol. Pathobionts of the intestinal microbiota and inflammatory disease. 23: 473-80. Thus, a pathobiont is a pathogen that is mechanistically distinct from an acquired infectious organism. Thus, the term “pathogen” includes both acquired infectious organisms and pathobionts.

As used herein, the term “immunoregulator” refers to an agent or a signaling pathway (or a component thereof) that regulates an immune response. “Regulating,” “modifying” or “modulating” an immune response refers to any alteration of the immune system or in the activity of such cell. Such regulation includes stimulation or suppression of the immune system which may be manifested by an increase or decrease in the number of various cell types, an increase or decrease in the activity of these cells, or any other changes which can occur within the immune system. Both inhibitory and stimulatory immunoregulators have been identified, some of which may have enhanced function or utility as a therapeutic target in a cancer microenvironment.

As used herein, the term “immune evasion” refers to inhibition of a subject's immune system or a component thereof (e.g., endogenous T cell response) by a cancer or tumor cell in order to maximize or allow continued growth or spread of the cancer/tumor.

As used herein, the term “immunotherapy” refers to the treatment or prevention of a disease or condition (e.g., cancer) by a method comprising inducing, enhancing, suppressing or otherwise modifying an immune response.

As used herein, “potentiating an endogenous immune response” means increasing the effectiveness or potency of an existing immune response in a subject. This increase in effectiveness and potency may be achieved, for example, by overcoming mechanisms that suppress the endogenous host immune response or by stimulating mechanisms that enhance the endogenous host immune response.

As used herein, the term “antibody” refers to a whole antibody molecule or a fragment thereof (e.g., fragments such as Fab, Fab′, and F(ab′)2), it may be a polyclonal or monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, etc.

As used herein, “cancer” means all types of cancers. In particular, the cancers can be solid or non-solid cancers. Non-limiting examples of cancers are carcinomas or adenocarcinomas such as breast, prostate, ovary, lung, pancreas or colon cancer, sarcomas, lymphomas, melanomas, leukemias, germ cell cancers and blastomas.

II. Methods of the Disclosure

Provided herein are compositions and methods for treatment and/or prevention of a cancer by microbiome manipulation. In particular, the amount, identity, presence, and/or ratio of bacteria in the microbiome (e.g., GI microbiome) in a subject is manipulated to facilitate treatment of a cancer. Furthermore, applicants have discovered that the abundance and/or prevalence of certain commensal bacteria in feces, e.g., commensal Ruminococcaceae, can be used to identify fecal donors and/or donations that can improve patient response to a checkpoint inhibitor. Fecal material from such individuals can be used, e.g., in fecal microbiome transplantation or in a processed form derived from such material, for example a preparation enriched in Firmicutes (e.g., Clostridia, Clostridiales, or spore formers), that are in vegetative and/or spore form.

Applicants have identified bacterial species that are useful for increasing the efficacy of cancer treatment, e.g., treatments using checkpoint inhibitors. In some embodiments, the effectiveness of an endogenous immune response, immunotherapy, chemotherapeutic, or other treatment (e.g., surgery, radiation, etc.) in the treatment or prevention of reoccurrence of cancer and/or tumor is dependent upon conditions within the subject (e.g., the tumor microenvironment). In particular, the identity or characteristics (e.g., concentration or level) of the microbiome within a subject can affect the effectiveness of cancer treatments (e.g., generally or specific treatments) and/or the effectiveness of the subject's own response to cancer, e.g., immune response.

In some embodiments, the presence or increased level of one or more species of bacteria in a subject facilitates treatment (e.g., immunotherapy, chemotherapy, etc.) and/or the subject's endogenous immune response to cancer and/or tumor cells. In some embodiments, the absence and/or decreased level of one or more species of bacteria in a subject discourages cancer/tumor growth, spread, and/or evasion of treatment/immune response. In some embodiments, the absence or decreased level of one or more species of bacteria in a subject facilitates treatment (e.g., immunotherapy, chemotherapy, etc.) and/or the subject's endogenous immune response to cancer and/or tumor cells.

In some embodiments, the presence of certain microbes (e.g., microbes that facilitate cancer treatment) in a subject creates an environment or microenvironment (e.g., microbiome) that is conducive to the treatment of cancer and/or inhibits cancer/tumor growth. In some embodiments, the presence of detrimental microbes (e.g., microbes that facilitate cancer/tumor growth and/or prevent treatment) in a subject creates an environment or microenvironment (e.g., microbiome) that is conducive to the treatment of cancer and/or inhibits cancer/tumor growth. Microbes or their products may act locally at the level of the gut epithelium and the lamina propria to alter immunological tone or immune cell trafficking, or they may act distally by the translocation of microbes or their products into circulation to alter peripheral immune responses, e.g. in blood, liver, spleen, lymph nodes or tumor.

Modulation of microflora levels and/or identity may comprise encouraging or facilitating growth of one or more species of beneficial microbes (e.g., microbes that facilitate cancer treatment), discouraging or inhibiting growth of one or more types of detrimental microbes (e.g., species of bacteria that facilitate cancer/tumor growth and/or prevent treatment), administering one or more types of beneficial microbes (e.g., species of bacteria that facilitate cancer treatment) to the subject, and/or combinations thereof. Embodiments within the scope herein are not limited by the mechanisms for introducing one or more microbes (e.g., probiotic administration, fecal transplant, etc.), encouraging growth of beneficial microbes (e.g., administering agents that skew the environment within the subject toward growth conditions for the beneficial microbes), discouraging or inhibiting growth of detrimental microbes (e.g., administering agents that skew the environment within the subject away from growth conditions for the detrimental microbes, administration of antimicrobial(s), etc.), and combinations thereof.

In some embodiments, methods are provided for the treatment or prevention of cancer by the manipulation of the presence, amount, or relative ratio of one or more families, genera, or species of bacteria (e.g., in the gastrointestinal microbiome). In some embodiments, the presence, amount, or relative ratio of particular bacteria, fungi, and/or archaea within a subject is altered. For example, in some embodiments, the presence, amount, or relative ratio of one or more bacteria from the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum is manipulated. For example, in some embodiments, the presence, amount, or relative ratio of one or more bacteria from the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, or Parabacteroides is manipulated. In some embodiments, the presence, amount, or relative ratio of one or more bacteria from the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, or Parabacteroides are manipulated. In some embodiments the presence, amount, or relative ratio of one or more bacteria from the genera Bifidobacterium, Blautia, Parabacteroides, or Subdoligranulum are manipulated. In some embodiments the presence, amount, or relative ratio of one or more bacteria from the genera Blautia, Clostridium, Coprococcus, Faecalibacterium, Fusicatenbacter, Gemmiger, Lachnospiraceae or Subdoligranulum are manipulated.

In some embodiments, the presence, amount or relative ratio of one or more bacterial species that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii are manipulated or adjusted. In some embodiments, the presence, amount or relative ratio of one or more bacterial species that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae are manipulated or adjusted. In some embodiments, the one or more species may have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the presence, amount or relative ratio of one or more bacterial species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof, are manipulated or adjusted.

In some embodiments, the methods exclude the administration of, the evaluation of, the detection of, or the determination of the amount or relative ratio of one or more bacterial species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.

In some embodiments, the presence, amount, or relative ratio of one or more bacterial species Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme or Parabacteroides distasonis are manipulated. In some embodiments, the presence, amount, or relative ratio of one or more bacterial species Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus or Parabacteroides distasonis are manipulated. In some embodiments, the presence, amount, or relative ratio of one or more bacterial species Bifidobacterium bifidum, Blautia_SC109, Parabacteroides distasonis Gemmiger formicilis or Subdoligranulum variabile are manipulated. In some embodiments, the presence, amount, or relative ratio of one or more bacterial species Blautia_SC109, Gemmiger formicilis or Subdoligranulum variabile, Coprococcus catus, Faecalibacterium prausnitzii, Fusicatenbacter saccharivorans, Gemmiger formicilis, Subdoligranulum variabile, Anaerostipes hadrus, Gemmiger formicilis or Subdoligranulum variabile are manipulated.

III. Therapeutic Compositions

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof. In some embodiments, the therapeutic composition may comprise bacteria belonging to at least one, two, three or four of the genera listed.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of one or more bacterial species that are phylogenetic descendants of the MRCA of Faecalibacterium prausnitzii and Flavonifractor plautii. In some embodiments, the therapeutic composition may comprise at least one, two, three, four, five, six, seven, eight, nine, ten or more than ten species that are phylogenetic descendants of the MRCA of Faecalibacterium prausnitzii and Flavonifractor plautii.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of one or more bacterial species that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the therapeutic composition may comprise at least one, two, three, four, five, six, seven, eight, nine, ten or more than ten species that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae. In some embodiments, the one or more species may have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of one or more bacterial species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof. In some embodiments, the therapeutic composition may comprise at least one, two, three, four, five, six, seven, eight, nine, ten or more than ten species of the species listed.

In some embodiments, the therapeutic compositions may exclude an isolated and/or purified population comprising one or more bacterial species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In some embodiments, the therapeutic composition may comprise bacteria belonging to at least one, two, three, four, five, six, seven, eight, nine or ten of the genera listed.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof. In some embodiments, the therapeutic composition may comprise bacteria belonging to at least one, two, three, four, five or six of the genera listed.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of bacteria belonging to one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In some embodiments, the therapeutic composition may comprise bacteria belonging to at least one, two, three, four, five or six of the genera listed.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In some embodiments, the therapeutic composition may comprise at least one, two, three, four, five, six, seven, eight, nine, ten, eleven or twelve of the species listed.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof. In some embodiments, the therapeutic composition may comprise at least one, two, three, four, five or six of the species listed.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof. In some embodiments, the therapeutic composition may comprise at least two, three, four, five or more of the species listed. In some embodiments, the therapeutic composition may comprise at least one, two, three, four, five, six, seven or eight of the species listed.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of one or more of the bacteria species in one or more of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135 as shown in the phylogenetic tree in FIG. 6. In some embodiments, clade 101 comprises the bacterial species Flavonifractor plautii, Clostridium orbiscindens, Clostridium sp NML_04A032, Pseudoflavonifractor capillosus, Ruminococcaceae bacterium D16, Clostridium viride, Oscillospira guilliermondii, Oscillibacter sp_G2, Oscillibacter valericigenes, Sporobacter termitidis and Paplillibacter cinnamivorans. In some embodiments, clade 14 comprises the bacterial species Ruminococcus sp_18P13, Ruminococcus sp_9SE51, Ruminococcus champanellensis, Ruminococcus callidus, Ruminococcus flavefaciens and Ruminococcus albus. In some embodiments, clade 126 comprises the bacterial species Ethanoligenens harbinense, Clostridium cellulosi, Acetanaerobacterium elongatum, Clostridium sp_YIT_12070, Clostridium methylpentosum, Hydrogenoanaerobacterium saccharovorans, and Anaerotruncus colihominis. In some embodiments, clade 61 comprises the bacterial species Eubacterium siraeum, Subdoligranulum variabile, Gemmiger formicilis and Faecalibacterium prausnitzii. In some embodiments, clade 125 comprises the bacterial species Eubacterium coprostanoligenes, Clostridium sp_YIT_12069, Clostridium sporosphaeroides, Clostridium leptum and Ruminococcus bromii. In some embodiments, clade 135 comprises the bacterial species Eubacterium desmolans, Butyricicoccus pullicaecorum or combinations thereof.

In some embodiments, the therapeutic compositions comprise an effective amount of one, two, three, four, five, six, seven, eight, nine, ten or eleven species of clade 101. In some embodiments, the therapeutic compositions comprise an effective amount of one, two, three, four, five or six, species of clade 14. In some embodiments, the therapeutic compositions comprise an effective amount of one, two, three, four, five, six or seven species of clade 126. In some embodiments, the therapeutic compositions comprise an effective amount of one, two, three or four species of clade 61. In some embodiments, the therapeutic compositions comprise an effective amount of one, two, three, four or five species of clade 125. In some embodiments, the therapeutic compositions comprise an effective amount of one or two species of clade 135.

In some embodiments, the therapeutic compositions may comprise additional species that are determined to be part of any one of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135. A person of ordinary skill in the art would be able to use methods known in the art to determine whether a species is part of a clade, including methods described herein.

In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of one or more of the bacteria species listed in Tables 1A and 1B. In some embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of one or more of the bacteria species listed in Table 11. In other embodiments, the therapeutic compositions comprise an effective amount of an isolated and/or purified population of one or more of the bacteria species listed in any of Tables 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10 and 11.

In some embodiments, a therapeutic composition can reduce the rate of tumor growth in an animal model. In some embodiments, a therapeutic composition can reduce the rate of tumor growth in a human subject. In some embodiments, a therapeutic composition can reduce the rate of tumor growth in an in vitro cell culture model. In some embodiments, a therapeutic composition can reduce the rate of tumor growth in an in situ model.

In some embodiments, the method of treating a cancer may use any of the therapeutic compositions listed herein, including combinations of genera from therapeutic compositions and/or combinations of species from therapeutic compositions. These methods of treatment, including combination treatment with other anti-cancer agents, are described in further detail below.

In some embodiments, the bacteria in the therapeutic compositions may be identified by species, operational taxonomic unit (OTU), whole genome sequence or other methods known in the art for defining different types of bacteria.

Bacterial compositions may comprise two types of bacteria (termed “binary combinations” or “binary pairs”) or greater than two types of bacteria. Bacterial compositions that comprise three types of bacteria are termed “ternary combinations”. For instance, a bacterial composition may comprise at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21, 22, 23, 24, 25, 26, 27, 28, 29 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or at least 40, at least 50 or greater than 50 types of bacteria, as defined by species or operational taxonomic unit (OTU), or otherwise as provided herein.

In another embodiment, the number of types of bacteria present in a bacterial composition is at or below a known value. For example, in such embodiments the bacterial composition comprises 50 or fewer types of bacteria, such as 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, or 10 or fewer, or 9 or fewer types of bacteria, 8 or fewer types of bacteria, 7 or fewer types of bacteria, 6 or fewer types of bacteria, 5 or fewer types of bacteria, 4 or fewer types of bacteria, or 3 or fewer types of bacteria. In another embodiment, a bacterial composition comprises from 2 to no more than 40, from 2 to no more than 30, from 2 to no more than 20, from 2 to no more than 15, from 2 to no more than 10, or from 2 to no more than 5 types of bacteria.

A bacterial composition useful in a method described herein may be prepared comprising at least one type of isolated bacteria, wherein a first type and a second type are independently chosen from the genera or species listed herein. In another embodiment, the first and/or second OTUs may be characterized by one or more of the variable regions of the 16S sequence (V1-V9). These regions in bacteria are defined by nucleotides 69-99, 137-242, 433-497, 576-682, 822-879, 986-1043, 1117-1173, 1243-1294 and 1435-1465 respectively using numbering based on the E. coli system of nomenclature. (e.g., Brosius et al., Complete nucleotide sequence of a 16S ribosomal RNA gene from Escherichia coli, Proc Nat Acad Sci 75(10):4801-4805 (1978)). In some embodiments, at least one of the V1, V2, V3, V4, V5, V6, V7, V8, and V9 regions are used to characterize an OTU. In one embodiment, the V1, V2, and V3 regions are used to characterize an OTU. In another embodiment, the V3, V4, and V5 regions are used to characterize an OTU. In another embodiment, the V4 region is used to characterize an OTU.

Methods of the disclosure include administration of a combination of therapeutic agents and compositions. The therapy may be administered in any suitable manner known in the art. For example, the therapies may be administered sequentially (at different times) or concurrently (at the same time). In some embodiments, the therapies are in a separate composition. In some embodiments, the therapies are in the same composition.

Various combinations of the therapies may be employed, for example, one therapy or composition designated “A” and another therapy or composition designated “B”:

A/B/A B/A/B B/B/A A/A/B A/B/B B/A/A A/B/B/B B/A/B/B

B/B/B/A B/B/A/B A/A/B/B A/B/A/B A/B/B/A B/B/A/A

B/A/B/A B/A/A/B A/A/A/B B/A/A/A A/B/A/A A/A/B/A

The therapies and compositions of the disclosure may be administered by the same route of administration or by different routes of administration. In some embodiments, the therapy is administered intracolonically, intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, intrathecally, intraventricularly, or intranasally. In some embodiments, the microbial modulator is administered intravenously, intramuscularly, subcutaneously, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, intrathecally, intraventricularly, or intranasally.

In some embodiments, the compositions of the disclosure are administered in a therapeutically effective or sufficient amount of each of the at least one isolated or purified population of bacteria or each of the at least two, 3, 4, 5, 6, 7, 8, 9, 10 11, 12, 13, 14, or 15 isolated or purified populations of bacteria of the microbial modulator compositions of the embodiments that is administered to a human will be at least about 1×10³viable colony forming units (CFU) of bacteria or at least about 1×10⁴, 1×10⁵, 1×10⁶, 1×10⁷, 1×10⁸, 1×10⁹, 1×10¹⁰, 1×10¹¹, 1×10¹², 1×10¹³, 1×10¹⁴, 1×10¹⁵viable CFU (or any derivable range therein). In some embodiments, a single dose will contain an amount of bacteria (such as a specific bacteria or species, genus, or family described herein) of at least, at most, or exactly 1×10⁴, 1×10⁵, 1×10⁶, 1×10⁷, 1×10⁸, 1×10⁹, 1×10¹⁰, 1×10¹¹, 1×10¹², 1×10¹³, 1×10¹⁴, 1×10¹⁵or greater than 1×10¹⁵viable CFU (or any derivable range therein) of a specified bacteria. In some embodiments, a single dose will contain at least, at most, or exactly 1×10⁴, 1×10⁵, 1×10⁶, 1×10⁷, 1×10⁸, 1×10⁹, 1×10¹⁰, 1×10¹¹, 1×10¹², 1×10¹³, 1×10¹⁴, 1×10¹⁵or greater than 1×10¹⁵viable CFU (or any derivable range therein) of total bacteria. In specific embodiments, the bacteria are provided in spore form or as sporulated bacteria. In particular embodiments, the concentration of spores of each isolated or purified population of bacteria, for example of each species, subspecies or strain, is at least, at most, or exactly 1×10⁴, 1×10⁵, 1×10⁶, 1×10⁷, 1×10⁸, 1×10⁹, 1×10¹⁰, 1×10¹¹, 1×10¹², 1×10¹³, 1×10¹⁴, 1×10¹⁵or greater than 1×10¹⁵(or any derivable range therein) viable bacterial spores per gram of composition or per administered dose. In some embodiments, the composition comprises or the method comprises administration of at least, at most, or exactly 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 40, or 50 (or any derivable range therein) of different bacterial species, different bacterial genus, or different bacterial family.

In some embodiments, the therapeutically effective or sufficient amount of each of the at least one isolated or purified population of bacteria or each of the at least two, 3, 4, 5, 6, 7, 8, 9, 10 11, 12, 13, 14, or 15 isolated or purified populations of bacteria of the microbial modulator compositions of the embodiments that is administered to a human will be at least about 1×103 cells of bacteria or at least about 1×10⁴, 1×10⁵, 1×10⁶, 1×10⁷, 1×10⁸, 1×10⁹, 1×10¹⁰, 1×10¹¹, 1×10¹², 1×10¹³, 1×10¹⁴, 1×10¹⁵cells (or any derivable range therein). In some embodiments, a single dose will contain an amount of bacteria (such as a specific bacteria or species, genus, or family described herein) of at least, at most, or exactly 1×10⁴, 1×10⁵, 1×10⁶, 1×10⁷, 1×10⁸, 1×10⁹, 1×10¹⁰, 1×10¹¹, 1×10¹², 1×10¹³, 1×10¹⁴, 1×10¹⁵cells (or any derivable range therein) of a specified bacteria. In some embodiments, a single dose will contain at least, at most, or exactly 1×10⁴, 1×10⁵, 1×10⁶, 1×10⁷, 1×10⁸, 1×10⁹, 1×10¹⁰, 1χ10¹¹, 1×10¹², 1χ10¹³, 1×10¹⁴, 1×10¹⁵cells (or any derivable range therein) of total bacteria. In specific embodiments, the bacteria are provided in spore form or as sporulated bacteria. In particular embodiments, the concentration of spores of each isolated or purified population of bacteria, for example of each species, subspecies or strain, is at least, at most, or exactly 1×10⁴, 1×10⁵, 1×10⁶, 1×10⁷, 1×10⁸, 1×10⁹, 1×10¹⁰, 1×10¹¹, 1×10¹², 1×10¹³, 1×10¹⁴, 1×10¹⁵or greater than 1×10¹⁵(or any derivable range therein) viable bacterial spores per gram of composition or per administered dose. In some embodiments, the composition comprises or the method comprises administration of at least, at most, or exactly 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 40, or 50 (or any derivable range therein) of different bacterial species, different bacterial genus, or different bacterial family.

The treatments may include various “unit doses.” Unit dose is defined as containing a predetermined-quantity of the therapeutic composition. The quantity to be administered, and the particular route and formulation, is within the skill of determination of those in the clinical arts. A unit dose need not be administered as a single injection but may comprise continuous infusion over a set period of time. In some embodiments, a unit dose comprises a single administerable dose.

The quantity to be administered, both according to number of treatments and unit dose, depends on the treatment effect desired. An effective dose is understood to refer to an amount necessary to achieve a particular effect. In some embodiments, it is contemplated that doses in the range from 10 mg/kg to 200 mg/kg can affect the protective capability of these agents. Thus, it is contemplated that doses include doses of about 0.1, 0.5, 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, and 200, 300, 400, 500, 1000 μg/kg, mg/kg, μg/day, or mg/day or any range derivable therein. Furthermore, such doses can be administered at multiple times during a day, and/or on multiple days, weeks, or months.

In some embodiments, the therapeutically effective or sufficient amount of a therapeutic composition that is administered to a human will be in the range of about 0.01 to about 50 mg/kg of patient body weight whether by one or more administrations. In some embodiments, the therapeutic agent used is about 0.01 to about 45 mg/kg, about 0.01 to about 40 mg/kg, about 0.01 to about 35 mg/kg, about 0.01 to about 30 mg/kg, about 0.01 to about 25 mg/kg, about 0.01 to about 20 mg/kg, about 0.01 to about 15 mg/kg, about 0.01 to about 10 mg/kg, about 0.01 to about 5 mg/kg, or about 0.01 to about 1 mg/kg administered daily, for example. In some embodiments, the therapeutic agent is administered at 15 mg/kg. However, other dosage regimens may be useful. In one embodiment, a therapeutic agent described herein is administered to a subject at a dose of about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg or about 1400 mg on day 1 of 21-day cycles. The dose may be administered as a single dose or as multiple doses (e.g., 2 or 3 doses), such as infusions. The progress of this therapy is easily monitored by conventional techniques.

In some embodiments, the effective dose of the pharmaceutical composition is one which can provide a blood level of about 1 μM to 150 μM. In another embodiment, the effective dose provides a blood level of about 4 μM to 100 μM; or about 1 μM to 100 μM; or about 1 μM to 50 μM; or about 1 μM to 40 μM; or about 1 μM to 30 μM; or about 1 μM to 20 μM; or about 1 μM to 10 μM; or about 10 μM to 150 μM; or about 10 μM to 100 μM; or about 10 μM to 50 μM; or about 25 μM to 150 μM; or about 25 μM to 100 μM; or about 25 μM to 50 μM; or about 50 μM to 150 μM; or about 50 μM to 100 μM (or any range derivable therein). In other embodiments, the dose can provide the following blood level of the agent that results from a therapeutic agent being administered to a subject: about, at least about, or at most about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 μM or any range derivable therein. In some embodiments, the therapeutic agent that is administered to a subject is metabolized in the body to a metabolized therapeutic agent, in which case the blood levels may refer to the amount of that agent. Alternatively, to the extent the therapeutic agent is not metabolized by a subject, the blood levels discussed herein may refer to the unmetabolized therapeutic agent.

Precise amounts of the therapeutic composition also depend on the judgment of the practitioner and are peculiar to each individual. Factors affecting dose include physical and clinical state of the patient, the route of administration, the intended goal of treatment (alleviation of symptoms versus cure) and the potency, stability and toxicity of the particular therapeutic substance or other therapies a subject may be undergoing.

It will be understood by those skilled in the art and made aware that dosage units of μg/kg or mg/kg of body weight can be converted and expressed in comparable concentration units of μg/ml or mM (blood levels), such as 4 μM to 100 μM. It is also understood that uptake is species and organ/tissue dependent. The applicable conversion factors and physiological assumptions to be made concerning uptake and concentration measurement are well-known and would permit those of skill in the art to convert one concentration measurement to another and make reasonable comparisons and conclusions regarding the doses, efficacies and results described herein.

IV. Methods for Evaluating Bacteria

A. Determining Bacterial Genera and Species

In some embodiments, the bacterial genera or species for use in a therapeutic composition is as described in the Examples below.

In some embodiments, the bacterial genera or species for use in a therapeutic composition are those genera or species that are found to be prevalent in the microbiome of subjects that respond to an anti-cancer therapy, e.g., subjects who are responders. In some embodiments, the genera or species are more prevalent in the microbiome of a responder compared to the microbiome of a subject who does not respond to an anti-cancer therapy, e.g., a non-responder. In other embodiments, the genera or species are more prevalent in the microbiome of a responder compared to the microbiome of a healthy subject that does not have a cancer and thus has not been treated with an anti-cancer therapy.

In some embodiments, the bacterial genera or species for use in a therapeutic composition are those genera or species that are found to be more abundant in the microbiome of subjects that respond to an anti-cancer therapy, e.g., subjects who are responders. In some embodiments, the genera or species are more abundant in the microbiome of a responder compared to the microbiome of a subject who does not respond to an anti-cancer therapy, e.g., a non-responder. In other embodiments, the genera or species are more abundant in the microbiome of a responder compared to the microbiome of a healthy subject that does not have a cancer and thus has not been treated with an anti-cancer therapy.

In some embodiments, whether a subject is a responder to an anti-cancer therapy is determined as described in the art, for example, by Routy et al. (Science 2018 359(6371):91-97) or Gopalakrishnan et al. (Science 2018; 359(6371):97-103). In some embodiments, the subject is considered a responder if, following treatment with an anti-cancer therapy, the subject shows a complete response to the therapy, e.g., a complete remission of the cancer. In other embodiments, the subject is considered a responder if, following treatment with an anti-cancer therapy, the subject shows a complete response to the therapy or a partial response to the therapy, e.g., a reduction in tumor size or tumor load. In other embodiments, the subject is considered a responder if, following treatment with an anti-cancer therapy, the subject shows a complete response to the therapy, a partial response to the therapy, or a stable response to the therapy, e.g. the subject's tumor size or tumor load does not increase.

B. Methods for Determining Species that are Members of the Family Ruminococcaceae

1. Most Recent Common Ancestor (MRCA)

In some embodiments, a bacterial species is a member of the family Ruminococcaceae if the species is a phylogenetic descendant of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii. In certain aspects, such a group of MRCA phylogenetic descendants is referred to as a “monophyletic” group.

In some embodiments, determining if a bacterial species is a descendant of a MRCA of Faecalibacterium prausnitzii and Flavonifractor plautii may be performed using phylogenetic grouping procedures known in the art. In one embodiment, one may use a rooted phylogenetic tree with F. prausnitzii, F. plautii and a third taxon of interest (e.g. a taxon to be classified), and apply the analysis packages Analyses of Phylogenetics and Evolution (“ape;” https://cran.r-project.org/web/packages/ape/index.html) and Phylogenetic Tools for Comparative Biology (and Other Things) (“phytools;” https://cran.r-project.org/web/packages/phytools/index.html) in order to determine whether the taxon of interest is in the family Ruminococcaceae. Both ape and phytools are packages written in the R language for use in studying molecular evolution and phylogenetics. The ape and phytools packages provide methods for phylogenetic and evolutionary analysis and their use is known to one of skill in the art.

In some embodiments, the following script may be used:

library(“ape”)

library(“phytools”)

input.tree = read.tree(file=″tree_file″)

rumino.node = getMRCA(input.tree,

c(′Faecalibacterium_prausnitzii′,′Flavonifractor_plautii′))

rumino.tree = extract.clade(input.tree, rumino.node)

print(rumino.tree$tip.label)

In some embodiments, after the script is run, if the taxon of interest is in the printed list, it is a descendant of a MRCA of Faecalibacterium prausnitzii and Flavonifractor plautii and, in certain aspects, a member of the family Ruminococcaceae.

In other embodiments, different phylogenetic grouping methods known in the art may be used to determine if a bacterial strain is a descendant of a MRCA of Faecalibacterium prausnitzii and Flavonifractor plautii, including methods that use different analysis packages and are based on different programming languages.

2. 16S rDNA Sequence Identity

In other embodiments, a bacterial species is a member of the family Ruminococcaceae if the species has a 16S rDNA sequence with sequence identity to 16S rDNA sequences from species already idenfied as a member of the family Ruminococcaceae. In an embodiment, identification of whether a bacterial species is a member of the family Ruminococcaceae is performed using the methods described in Yarza et al., 2014, Nature Reviews Microbiology 12:635-645, and Stackebrandt, E. & Ebers, J., 2006, Microbiol. Today 8:6-9, which are hereby incorporated by reference herein.

In some embodiments, the 16S rDNA sequence is obtained or determined for a bacterial species to be classified. This query 16S rDNA sequence is compared to 16S rDNA sequences from bacterial species already classified as members of the family Ruminococcaceae. In some embodiments, the query 16S rDNA sequence is compared to the 16S rDNA sequences listed in Table 11. In some embodiments, the query 16S rDNA sequence is compared to all known 16S rDNA sequences for bacterial species already classified as members of the family Ruminococcaceae. In other embodiments, the query 16S rDNA sequence is compared to a subset of all known 16S rDNA sequences for bacterial species already classified as members of the family Ruminococcaceae. A percent identity between the query sequence and the compared sequences is determined. If the percent identify of the query sequence is determined to be above a defined threshold, then the bacterial species to be classified is classified as member of the family Ruminococcaceae.

In some embodiments, the threshold sequence identity is 94.5%. In some embodiments, the threshold sequence identity is 98.7%. In some embodiments, the threshold sequence identity is 94.8%. In some embodiments, the threshold sequence identity is 94.5%, 94.6%, 94.7%, 94.8%, 94.9%, 95.0%, 95.1%, 95.2%, 95.3%, 95.4%, 95.5%, 95.6%, 95.7%, 95.8%, 95.9%, 96.0%, 96.1%, 96.2%, 96.3%, 96.4%, 96.5%, 96.6%, 96.7%, 96.8%, 96.9%, 97.0%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98.0%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9% 99.0%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%. 99.6%, 99.7%, 99.8%, 99.9% or 100%.

3. Clades that are Part of the Family Ruminococcaceae

In some embodiments, bacteria species may be classified in one of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135 as shown in the phylogenetic tree in FIG. 6. In some embodiments, clade 101 comprises the bacterial species Flavonifractor plautii, Clostridium orbiscindens, Clostridium sp NML_04A032, Pseudoflavonifractor capillosus, Ruminococcaceae bacterium D16, Clostridium viride, Oscillospira guilliermondii, Oscillibacter sp_G2, Oscillibacter valericigenes, Sporobacter termitidis and Paplillibacter cinnamivorans. In some embodiments, clade 14 comprises the bacterial species Ruminococcus sp_18P13, Ruminococcus sp_9SE51, Ruminococcus champanellensis, Ruminococcus callidus, Ruminococcus flavefaciens and Ruminococcus albus. In some embodiments, clade 126 comprises the bacterial species Ethanoligenens harbinense, Clostridium cellulosi, Acetanaerobacterium elongatum, Clostridium sp_YIT_12070, Clostridium methylpentosum, Hydrogenoanaerobacterium saccharovorans, and Anaerotruncus colihominis. In some embodiments, clade 61 comprises the bacterial species Eubacterium siraeum, Subdoligranulum variabile, Gemmiger formicilis and Faecalibacterium prausnitzii. In some embodiments, clade 125 comprises the bacterial species Eubacterium coprostanoligenes, Clostridium sp_YIT_12069, Clostridium sporosphaeroides, Clostridium leptum and Ruminococcus bromii. In some embodiments, clade 135 comprises the bacterial species Eubacterium desmolans, Butyricicoccus pullicaecorum or combinations thereof.

In some embodiments, the clades herein can include additional species that are determined to be part of any one of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135. In some embodiments, the phylogenetic grouping methods described herein, including the MRCA and 16S rDNA sequence identity methods described above, may be used to determine in an additional species belongs in a clade. In some embodiments, an additional species is classified as part of a clade if the 16S rDNA of the additional species is at least 97% identical to the 16S rDNA of the other species in the clade. A person of ordinary skill in the art would also be able to use methods known in the art to determine whether a species is part of a clade, including methods described herein.

C. Methods for Determining 16S rDNA Sequences

Operational taxonomic units (OTUs) can be identified, for example, by sequencing of the 16S rRNA gene, by sequencing of a specific hypervariable region of this gene (i.e. V1, V2, V3, V4, V5, V6, V7, V8, or V9), or by sequencing of any combination of hypervariable regions from this gene (e.g. V1-3 or V3-5). The bacterial 16S rDNA is approximately 1500 nucleotides in length and is used in reconstructing the evolutionary relationships and sequence similarity of one bacterial isolate to another using phylogenetic approaches. 16S rDNA sequences are used for phylogenetic reconstruction as they are in general highly conserved, but contain specific hypervariable regions that harbor sufficient nucleotide diversity to differentiate genera and species of most microbes. Using well known techniques to determine a full 16S rDNA sequence or the sequence of any hypervariable region of the 16S rDNA sequence, genomic DNA is extracted from a bacterial sample, the 16S rDNA (full region or specific hypervariable regions) amplified using polymerase chain reaction (PCR), the PCR products cleaned, and nucleotide sequences delineated to determine the genetic composition of 16S rDNA gene or subdomain of the gene. If full 16S rDNA sequencing is performed, the sequencing method used may be, but is not limited to, Sanger sequencing. If one or more hypervariable regions are used, such as the V4 region, the sequencing may be, but is not limited to being, performed using the Sanger method or using a next-generation sequencing method, such as an Illumina (sequencing by synthesis) method using barcoded primers allowing for multiplex reactions. In some cases, the 16S rDNA sequence associated with an OTU, species, or strain of bacteria is a composite of multiple 16S rDNA sequences harbored by the OTU, species, or strain.

In some embodiments, bacterial species identified as described herein are identified by sequence identity to 16S rDNA sequences as known in the art and described herein. In some embodiments, the selected species are identified by sequence identity to full length 16S rDNA sequences as shown in Table 10.

In some embodiments, Clostridium_SC64 is identified by at least 97% identity to the full length 16S rDNA sequence provided as SEQ ID NO:1 or at least 97% identity to a variable region such as V4. In some embodiments, Blautia_SC102 is identified by at least 97% to the full length 16S rDNA sequence provided as SEQ ID NO:2 or at least 97% identity to a variable region such as V4. In some embodiments, Blautia_SC109 is identified by its full length 16S rDNA sequence provided as SEQ ID NO:3 or at least 97% identity to a variable region such as V4. In some embodiments, Blautia_SC109 is identified by its full length 16S rDNA sequence provided as SEQ ID NO:4 or at least 97% identity to a variable region such as V4.

V. Methods for Preparing a Bacterial Composition for Administration to a Subject

Methods for producing bacterial compositions are known in the art. For example, a composition can be produced generally via three main processes, combined with one or more methods of mixing. The steps are: organism banking, organism production, and preservation.

For banking, the strains included in the bacterial composition can be, for example isolated directly from a specimen, obtained from a banked stock, optionally cultured on a nutrient agar or in broth that supports growth to generate viable biomass, and the biomass optionally preserved in multiple aliquots in long-term storage.

Stocks of organisms may prepared for storage, e.g., by adding cryoprotectants, lyoprotectants, and/or osmoprotectants. In general, such methods are known in the art.

VI. Immuno-Oncology (Immunotherapy) Drugs that can be Used in Conjunction with the Therapeutic Compositions

In some embodiments of the invention, the therapeutic composition is an adjunct treatment administered in combination with an immunotherapy drug, generally an immune checkpoint inhibitor (e.g., an antibody, such as a monoclonal antibody). The terms “immune checkpoint inhibitor,” “immune checkpoint blockade,” and “immune checkpoint therapy” are used interchangeably. Examples of such immunotherapy drugs include PD-1 inhibitors (e.g., nivolumab, and pembrolizumab), PD-L1 inhibitors (e.g., atezolizumab, avelumab, and durvalumab), and CTLA-4 inhibitors (e.g., ipilimumab and tremelimumab). In some embodiments, more than one checkpoint inhibitor is administered. As is known in the art, dosing of checkpoint inhibitors can be repeated at, for example, 2-3 week intervals, for as long as the patient continues to have a response or stable disease, or as otherwise determined to be appropriate by those of skill in the art.

Examples of cancers that can benefit from treatment with the therapeutic compositions in conjunction with a checkpoint inhibitor, e.g., an inhibitor of PD-1, PD-L1, or CTLA-4, include but are not limited to metastatic melanoma, melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, Merkel cell skin cancer (Merkel cell carcinoma), and Hodgkin lymphoma.

VII. Methods of Treatment

In general, the therapeutic compositions are administered to a patient diagnosed with a cancer, e.g., melanoma, for example, metastasized melanoma in conjunction with an immunotherapy drug such as checkpoint inhibitor, e.g., an inhibitor of PD-1, PD-L1, or CTLA-4. A therapeutic composition can be administered prior to checkpoint inhibitor (e.g., PD-1/PD-L1 inhibitor or CTLA-4 inhibitor) treatment, for example, at least one week, two weeks, or three weeks in advance of the treatment. In some cases, administration of the therapeutic composition is continued after the initiation of checkpoint inhibitor (e.g., PD-1/PD-L1 or CTLA-4 inhibitor) treatment. The therapeutic compositions may be administered daily, weekly, or monthly to induce and/or maintain an appropriate microbiome in the patient's GI tract.

Prior to initiating administration of a therapeutic composition, the patient may be subject to antibiotic treatment (e.g., with vancomycin, neomycin, rifaximin, or other antibiotic) and/or a bowel cleanse. In some cases, the antibiotic is a non-absorbable or minimally absorbable antibiotic. In some cases, no bowel preparation is performed. Such preparation may increase the speed and or efficacy of engraftment of one or more species in the therapeutic compositions that are associated with an improvement in checkpoint inhibitor (e.g., PD-1/PD-L1 inhibitor) efficacy.

VIII. Models for Testing

Animal models suitable for testing the efficacy of a microbiome composition for use in immunotherapy are known in the art, for example, as described in Cooper et al. (2014, Cancer Immunol Res 2:643-654) and Gopalakrishnan et al (2018, Science 359(6371):97-103) using the BP cell line, and reviewed in Li et al. (2017, Pharmacol & Therapeutics, dx.doi.org/10.1016/j.pharmthera.20170.02.002). Other useful models include germ-free mouse models (e.g., Matson et al. Science 359:104-108 (2018), Routy et al Science 59(6371):91-97 (2018)).

IX. Formulations

A microbiome immune-oncology therapeutic composition for use as described herein can be prepared and administered using methods known in the art. In general, compositions are formulated for oral, colonoscopic, or nasogastric delivery although any appropriate method can be used.

A formulation containing a therapeutic composition can contain one or more pharmaceutical excipients suitable for the preparation of such formulations. In some embodiments, the formulation is a liquid formulation. In some embodiments, a formulation comprising the therapeutic compositions can comprise one or more of surfactants, adjuvants, buffers, antioxidants, tonicity adjusters, thickeners or viscosity modifiers and the like.

In some embodiments, treatment includes administering the therapeutic compositions in a formulation that includes a pharmaceutically acceptable carrier. In some embodiments, the excipient includes a capsule or other format suitable for providing the therapeutic compositions as an oral dosage form. When an excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier or medium for the active ingredient. Thus, the formulations can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, soft or hard capsules, suppositories, or packaged powders.

Some examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, polyethylene glycol, glycerol, and methyl cellulose. The compositions can be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient by employing procedures known in the art.

In some embodiments, the therapeutic composition can be incorporated into a food product. In some embodiments the food product is a drink for oral administration. Non-limiting examples of a suitable drink include fruit juice, a fruit drink, an artificially flavored drink, an artificially sweetened drink, a carbonated beverage, a sports drink, a liquid diary product, a shake, an alcoholic beverage, a caffeinated beverage, infant formula and so forth. Other suitable means for oral administration include aqueous and nonaqueous solutions, emulsions, suspensions and solutions and/or suspensions reconstituted from non-effervescent granules, containing at least one of suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, coloring agents, and flavoring agents.

In some embodiments, the food product is a solid foodstuff. Suitable examples of a solid foodstuff include without limitation a food bar, a snack bar, a cookie, a brownie, a muffin, a cracker, an ice cream bar, a frozen yogurt bar, and the like.

In some embodiments, the therapeutic compositions are incorporated into a therapeutic food. In some embodiments, the therapeutic food is a ready-to-use food that optionally contains some or all essential macronutrients and micronutrients. In some embodiments, the compositions disclosed herein are incorporated into a supplementary food that is designed to be blended into an existing meal. In some embodiments, the supplemental food contains some or all essential macronutrients and micronutrients. In some embodiments, the bacterial compositions disclosed herein are blended with or added to an existing food to fortify the food's protein nutrition. Examples include food staples (grain, salt, sugar, cooking oil, margarine), beverages (juice, coffee, tea, soda, beer, liquor, sports drinks), snacks, sweets and other foods.

The therapeutic compositions can be formulated in a unit dosage form. In general, a dosage comprises about 1×10²to 1×10⁹viable colony forming units (CFU). The term “unit dosage forms” refers to physically discrete units suitable as unitary dosages for human subjects and/or other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient. A dosage may be administered in multiple delivery vehicles, e.g., multiple pills, capsules, foodstuffs or beverages.

The amount and frequency of administering the therapeutic compositions to a patient can vary depending upon the specific composition being administered, the purpose of the administration (such as prophylaxis or therapy), the state of the patient, the manner of administration, and the like. In therapeutic applications, compositions can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially arrest or mitigate the symptoms of the disease and its complications. An effective dose can depend on the disease condition being treated as well as by the judgment of the attending clinician depending upon factors such as the severity of the disease, the age, weight and general condition of the patient, and the like.

In some embodiments, at least one dose of the therapeutic composition is administered by the attending clinician or a person acting on behalf of the attending clinician. In some embodiments, the subject may self-administer some or all of the subsequent doses. In other embodiments, all doses of the therapeutic composition are administered by the attending clinician or a person acting on behalf of the attending clinician. In these embodiments, prior to the administration of a first dose of the therapeutic composition the attending clinician or a person acting on behalf of the attending clinician may administer an antibiotic treatment and/or a bowel cleanse.

The dosage can refer, for example, to the total number of viable colony forming units (CFUs) of each individual species or strain; or can refer to the total number of microorganisms in the dose. It is understood in the art that determining the number of organisms in a dosage is not exact and can depend on the method used to determine the number of organisms present. If the composition includes spores, for example, the number of spores in a composition may be determined using a dipicolinic acid assay (Fichtel et al, 2007, FEMS Microbiol Ecol, 61:522-32). In some cases, the number of organisms is determined using a culture assay.

Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems.

X. Methods of Identifying a Candidate for Immune Checkpoint Therapy in Combination with Adjuvant Microbiome Therapy

In some embodiments, methods are provided of identifying a subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the methods comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence or abundance of the genera or selected genera of bacteria in the microbiome sample, and c) determining that the subject is a candidate for anticancer treatment if the microbiome sample comprises bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof. In some embodiments, methods are provided of identifying a subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the methods comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence or abundance of the genera or selected genera of bacteria in the microbiome sample, and c) determining that the subject is a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy if the microbiome sample comprises bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In other embodiments, methods are provided of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the methods comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence and/or abundance of the genera of bacteria in the microbiome sample, and c) determining that the subject is a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy if the microbiome sample comprises one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof. In other embodiments, methods are provided of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the methods comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence and/or abundance of the genera of bacteria in the microbiome sample, and c) determining that the subject is a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy if the microbiome sample comprises one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.

In other embodiments, methods are provided of identifying a mammalian subject as a candidate for anticancer treatment, the methods comprising: a) obtaining a microbiome sample from the subject, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the subject is a candidate for anticancer treatment if the microbiome sample comprises one or more bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof. In some embodiments, the subject may be determined to be a candidate for anticancer treatment if at least two, three, four, five or more of the species listed are present in the microbiome sample.

In some embodiments, subjects that are identified as candidates for anticancer treatment are identified as candidates for treatment with a checkpoint inhibitor. In some embodiments, the checkpoint inhibitor can be an anti-PD-1 antibody, an anti-CTLA-4 antibody an anti-PD-L1 antibody or combinations thereof. In some embodiments, the checkpoint inhibitor can be, e.g., pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab or ipilimumab, or other checkpoint inhibitors known in the art. In other embodiments, the checkpoint inhibitors can be e.g., pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, BMS-936558, MK-3475, CT 011, MPDL3280A, MEDI-4736, MSB-0020718C, AUR-012, LAG-3, OX40 inhibitors, OX40L inhibitors, TIGIT inhibitors STI-A1010, or combinations thereof. In other embodiments, the subject can be candidates for treatment with cyclophosphamide. In some embodiments, the immune checkpoint therapy comprises immune checkpoint blockade monotherapy. In some embodiments, the immune checkpoint therapy comprises immune checkpoint blockade combination therapy.

XI. Methods of Identifying FMT Donors

Applicants have discovered that certain microbiome profiles, e.g., families, genera, and/or species are associated with improved outcomes in therapy with a checkpoint inhibitor. Accordingly, in some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof. In other embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof. In other embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.

In other embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof. In some embodiments, the potential donor may be determined to be a donor for fecal matter transfer if at least two, three, four, five or more of the species listed are present in the microbiome sample.

In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more of the bacteria species in one or more of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three, four, five, six, seven, eight, nine, ten or eleven species of clade 101. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three, four, five or six, species of clade 14. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three, four, five, six or seven species of clade 126. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three or four species of clade 61. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three, four or five species of clade 125. In some embodiments, the therapeutic compositions comprise an effective amount of one or two species of clade 135.

In other embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof. In some embodiments, the potential donor may be determined to be a donor for fecal matter transfer if at least two, three, four, five or more of the species listed are present in the microbiome sample.

In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more of the bacteria species in one or more of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three, four, five, six, seven, eight, nine, ten or eleven species of clade 101. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three, four, five or six, species of clade 14. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three, four, five, six or seven species of clade 126. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three or four species of clade 61. In some embodiments, methods are provided of selecting donors whose feces are useful for fecal matter transfer, the methods comprising: a) obtaining a microbiome sample from the potential donor, b) determining the abundance of the species of bacteria in the microbiome sample, and c) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one, two, three, four or five species of clade 125. In some embodiments, the therapeutic compositions comprise an effective amount of one or two species of clade 135.

Below are examples of specific embodiments for carrying out the present invention. The examples are offered for illustrative purposes only, and are not intended to limit the scope of the present invention in any way. Efforts have been made to ensure accuracy with respect to numbers used, but some experimental error and deviation should, of course, be allowed for.

XII. Examples
Example 1: Taxonomic Profiling

Whole metagenomics sequencing (WMS) raw data from Gopalakrishnan et al. (Science 2018; 359: 97-103) were obtained and analyzed as described herein. As described in Gopalakrishnan et al., supra, the WMS sequences were generated using fecal microbiome samples from metastatic melanoma patients who were classified as responders or non-responders to a checkpoint inhibitor. Responder and non-responder classes of subjects were determined as described in Gopalakrishnan et al. The raw data sets were pre-processed following the guidelines set by the Human Microbiome Project. The pre-processing analysis was used to perform error analysis and removal of low-quality sequences and other undesirable data, such as sequences present from PCR amplification steps. Species-level taxonomic profiles of each WMS sample were obtained using a MetaPhlAn2 software package (e.g., Truong et al., Nature Meth 12:902-903, 2015). In brief, MetaPhlAn2 is a software tool that aligns each sample to a curated reference database of marker genes, each of which is unique to a bacterial species. The reference database contains more than one million marker genes, representing more than seven thousand bacterial species. Alpha diversity, i.e., a measure of species richness, of 16S rDNA for responders (R) and non-responders (NR) is shown in FIG. 1.

Example 2: Summary of Data Types and Data Analysis Methods

Abundance data were obtained after profiling WMS data. For a given sample, the sum of the abundances of all species sums to 100. Prevalence data are discretized so that species are analyzed only as being either present or absent. This is a population-wide data type, meaning that it can only be assessed for a set of samples and not individually for any given sample. For example, the prevalence of a species that appears in 4 out of 10 responders is 40%. Quantile normalized abundance is a procedure that was used to standardize microarray data. Across data sets, estimated abundance values of a given species may lead to a different interpretation due to a variety of reasons including technical artifacts arising from differences in sample processing. The quantile normalization approach re-assigns abundance values of a species given the distribution of abundances of that species in a set of background samples (in this case, non-responders). The normalized value is the percentage of background samples that have an abundance less than or equal to the abundance of the given species in the given sample. A volcano plot of results from a differential prevalence analysis is shown in FIG. 2.

Using these three data types, four analytic methods were used to generate independent data sets: Fisher's exact test, Lasso regression, Random forest analysis, and Linear discriminant analysis. These analytic approaches are briefly described below. A table summarizing key features of the methods is provided in Table 9.

The Fisher's exact test is a test for a difference in distribution of categorical variables. Applicants applied this analysis to test for differences in species prevalence between responders and non-responders, given the number of samples found in each group. For example, a species that occurs in 8/12 responder samples would have a prevalence of 67%. Statistical significance is calculated between the prevalence of responders and non-responders based on the same size of each group.

The Lasso Regression is different from simple regression, where an effect is assigned to every feature in the data set (such as species abundance and/or prevalence). Instead, Lasso regression attempts to minimize small effects in order to retain the smallest collection of features that have the largest impact on outcome, using an L1 regularization approach. This approach attempts to avoid overfitting the data to all possible variables in the data set, and instead leads to more interpretable results.

The random forest classifier is an algorithm based on the results of many decision trees. In a single decision tree, features are selected iteratively that best separate samples into responder and non-responder categories, until all features are utilized. In the case of prevalence data, these features could be presence or absence of a given species, where presence of a single species might be preferentially associated with responder samples, or vice versa. Since a single decision tree typically overfits data and does not produce robust results, random forests are often used instead. A random forest classifier is based on many different decision trees, where each tree only uses a subset of the available data, for example randomly leaving out 20% of the observed species for each tree. In some cases, a subset of the samples is used for training the random forest. The random forest classifier thus learns which signals are strongest across all possible features and samples.

Linear discriminant analysis (LDA) is a method that attempts to find a linear combination of features that separates samples into two or more outcomes. For example, in a multidimensional scaling (MDS) representation of the Bray-Curtis dissimilarity among samples, the method can be applied to identify the species that distinguish responder from non-responder samples. Due to the limited sample size of the available data, and to provide additional information that might be present in a larger set of healthy background samples, this approach was applied to the data as embedded into approximately 200 samples from healthy donors as collected in the Human Microbiome Project (HMP). This was done by calculating the Bray-Curtis dissimilarity among all WMS and HMP samples. LDA was then used to generate a classification line to separate responder and non-responder samples in the data as embedded in the combined MDS plot (FIG. 3). Further, species data mapped onto a beta diversity plot demonstrates that Ruminococcaceae are generally associated with patients classified as responders (FIG. 4).

A ranking of the significance of association of taxa to responder and non-responder status can then be evaluated based on their distance from the classification line, where taxa that are further from the line (e.g. driving the signal of separation between R and NR) are given a higher score. In order to mitigate the significance of rare species which are found in very few samples, the score was modified by multiplying it by the log of the prevalence of the species in the pooled data. The effect of this final modification is that species with very low prevalence are assigned a lower significance score. Due to the fact that this list sets no cutoff threshold for statistical significance, we examined scores in a quantile-quantile style plot and selected the inflection point of scores as the cutoff.

Example 3: Development of Aggregate Results and Rankings Based on Penalized Geometric Mean Analysis

After obtaining a ranked list of species according to the various methods and data types above, a method of aggregating the rankings was developed that fulfill the following properties: species that are significantly associated with response were assigned higher ranks, species that were found significantly associated with response across multiple methods were assigned higher ranks compared to species that were found significantly associated in only one or two methods, and final species rankings were robust to potential outliers in individual method rankings. The first two properties are intuitive, since species that are identified as significant using multiple algorithms and data types are more likely to represent a real and robust signal. Because different algorithms may return a different number of significantly associated species, the third property was included to minimize the penalty for rankings based solely on significantly associated species. The aggregate results of the ranked lists generated by the alternate analysis methods are in Tables 1-2.

A penalized geometric mean approach was developed to generate the aggregate results. For each species, the geometric mean was calculated from its ranks across all methods in which it was identified. The geometric mean is defined as the product of all n values, followed by taking the n^throot. For example, for “Species Example 1” that was identified in three out of the four methods, the geometric mean of (1, 2, 10) would be (1×2×10)^(1/3)=2.71. This geometric mean is robust to outliers, but it is susceptible to bias for certain data sets, such as “Species Example 2” instead appearing in all four analysis methods with rankings 1, 2, 2, 20 across the four analysis methods (1, 2, 2, 20), since (1×2×2×20){circumflex over ( )}(¼)=2.99. Using this approach, Species Example 1, with a value of 2.71 would be ranked higher than Species Example 2 due to its lower geometric mean score, yet this approach does not account for the prevalence aspect of the analysis and the fact that Species Example 1 was not identified in one of the four analysis methods.

To account for this discrepancy, scores were penalized by the square of the number of methods in which a given species is not found. These aggregate scores are then ranked from lowest to highest, with lowest scores attributed to species for which we have the most confidence. Thus, better scores were preferentially assigned to those species which are identified as significant by a variety of different methods. Final aggregate rankings can be found in Tables 1-2.

These analyses demonstrate the in silico analysis of human microbiome data can be used to identify bacteria genera and species associated with a response to a checkpoint inhibitor. Accordingly, species identified as provided herein are useful in compositions for improving the efficacy of a checkpoint inhibitor treatment.

Example 4: Further Validation Studies

Several studies have reported various disparate GI microbiome signatures for individuals having an improved response to a checkpoint inhibitor. Applicants undertook a further analysis of data reported in Gopalakrishnan et al., 2018 to determine whether a signature could be detected that would be useful for identifying donor fecal material likely to be effective for the preparation of a microbiome composition useful as an adjunct therapy for treating patients receiving checkpoint inhibitor therapy.

It is desirable that detection of the signature has a rapid turnaround time and can be implemented, e.g., as a qPCR diagnostic. Validation of the signature using an additional cohort of patients selected by the laboratory of Dr. Jennifer Wargo using the same criteria for patient selection and identification of disease state as in Gopalakrishnan et al (2018) was then performed.

Terms & Abbreviations

The following terms and abbreviations are used in Example 4:

- Clade system: An internal numbered classification system based on the concept of clades, i.e. a group of related organisms representing all of the phylogenetic descendants of a common ancestor.
- RECIST: Response evaluation criteria in solid tumors. A set of guidelines to determine the response of tumors to therapy.
- refOTU: An internal classification system of 16S rDNA sequences assigned to specific taxonomies that is derived from NCBI and internal sources.
- Responders and non-responders: non-responders include patients within the RECIST category progressive disease, while responders include patients in the RECIST categories stable disease, partial response, and complete response.
- ROC curve: Receiver operating characteristic curve. A plot that shows the true positive and false positive rate of a binary classifier as the definition of the classifier is varied.
- OTU (Operational Taxonomic Unit): An operational definition of a group of closely related organisms outside of traditional Linnaean taxonomy.
- Silva: A widely used database of rDNA sequences and their classifications (https://www.arb-silva.de/).
- USEARCH: A suite of sequence searching and clustering algorithms developed by R. Edgar.
- Wargo Types: Gopalakrishnan et al (2018) divided patients into two microbiome types: Type 1 (enriched in Clostridiales) included only responders while Type 2 (enriched in Bacteroidales) included a mix of responders and non-responders.

A. Materials & Methods

1. Acquisition of Sequence Data

Human fecal 16S NGS sequencing (Illumina MiSeq) data from 43 patients (30 responders and 13 non-responders) from the Gopalakrishnan et al (2018) study were downloaded from the European Nucleotide Archive (ENA) of the European Bioinformatics Institute (EBI) (https://www.ebi.ac.uk/ena/data/view/ERX2218758, Experiment: ERX2218758, Project: PRJEB22894). Additional human fecal 16S NGS sequencing (Illumina MiSeq) data were obtained from the second cohort of 69 patients (39 responders and 30 non-responders).

2. Taxonomic Profiling of 16S Sequence Data Through USEARCH

Both published data and validation data were processed through the Seres USEARCH-based pipeline. Reads were merged using USEARCH v7.0.1090 (Edgar 2010, 2013) allowing four mismatches per ≥50 bases. Taxonomic annotations were assigned to 16S V4 sequence reads using the USEARCH v7.0.1090 (Edgar, 2010, 2013) algorithm. The USEARCH algorithm was parameterized to maximize sequence read data retention and to return the optimal taxonomy. Operational Taxonomic Unit (OTU) assignment based on 16S V4 sequence data is limited by the amount of information in the approximately 254 base pairs comprising this rDNA domain. To gain maximal information content from 16S V4 sequences, applicants developed a proprietary clade mapping system based on the ability of the 16S V4 region to reliably distinguish groups (clades) of related organisms. This system was used to define the phylogenetic clade that can be definitively assigned to any given OTU. As discussed herein, clades provide a resolution that is greater than genus assignment but typically less than species. These clades define the group of bacterial species that are not reliably distinguished from one another using the 16S V4 sequencing assay but can be distinguished from other bacterial species in other clades. Importantly, while the precise assignment of species is often not possible with 16S V4 data, the consistent determination of the number of distinct OTUs within a given clade is robust using the algorithms reported here.

3. Statistical Analysis

Mann-Whitney U tests were conducted on continuous or integer-based data (e.g., relative abundance, species diversity), while Fisher's exact tests were conducted on categorical data (e.g., Wargo Types). All p-values were corrected for multiple comparisons using the Benjamini-Hochberg method.

B. Results & Analysis

1. Type 1 Microbiomes are Enriched in Clostridia while Type 2 Microbiomes are Enriched in Bacteroidia

Gopalakrishnan et al (2018) subdivided patients into two microbiome types: Type 1 (enriched in Clostridiales), which included only patients defined by the authors as responders, and Type 2 (enriched in Bacteroidales), which included a mix of responders and non-responders. A USEARCH-based pipeline and NCBI-based genus-level classification were used to verify these compositional differences in the published 16S sequencing data. Differentially prevalent higher taxa at the levels of class and family were identified between Type 1 and Type 2 patients using a Mann-Whitney U test adjusted for multiple comparisons at each taxonomic level using the Benjamini-Hochberg method. Type 1 patients were enriched for Clostridia, particularly the families Ruminococcaceae, Lachnospiraceae, Clostridiaceae, and Catabacteriaceae, while Type 2 patients were enriched in Bacteroidia (Table 12). This enrichment is similar to that identified in Gopalakrishnan et al (2018) Table S5.

TABLE 12

Type 1 microbiomes are enriched in Clostridia while Type

2 microbiomes are enriched in Bacteroidia. All class- and

family-level taxa significantly enriched in either type

are shown below. Mann-Whitney U tests were conducted for

each taxon, and adjusted for multiple comparisons at each

taxonomic level using the Beniamini-Hochberg method.

Adj

Level
Taxon
Enrichment
P-value
P-value

Class
Bacterioidia
Type 2
1.4 × 10⁻⁹
2.6 × 10⁻⁸

Class
Clostridia
Type 1
2.3 × 10⁻⁷
2.2 × 10⁻⁶

Family
Ruminococcaceae
Type 1
0.0019
0.0068

Family
Lachnospiraceae
Type 1
0.00098
0.0046

Family
Clostridiaceae
Type 1
5.5 × 10⁻⁵
0.00076

Family
Catabacteriaceae
Type 1
0.00045
0.0032

2. Relative Abundance of Ruminococcaceae, Clostridia, and Bacteroidia are the Strongest Predictors of Response

Potential correlates of checkpoint efficacy were then evaluated by comparing directly with response rather than type. Both Wargo type and Clostridia species diversity were evaluated based on findings in Gopalakrishnan et al (2018), and the relative abundance of Clostridia, Bacteroidia, and Ruminococcaceae based on the analysis above. The relative abundance of Clostridiaceae and Lachnospiraceae was not evaluated further as their signal appeared to be driven by high abundances in a small number of samples. For each potential correlate, a statistical test was conducted to determine if there was a significant difference between responders and non-responders (Table 13). The specific test was determined by whether the correlate was categorical (Fisher's exact test) or numerical (Mann-Whitney U test). Ruminococcaceae, Clostridia, and Bacteroidia relative abundance, and Wargo type all differed significantly (p<0.05) between responders and non-responders, while Clostridia diversity (in OTUs) did not.

Next, for each potential correlate, a binary classification system was developed where the optimal cut-off was chosen to separate responders from non-responders based on first maximizing specificity (to 100% if possible) and then maximizing sensitivity using bar plots (FIG. 5, Table 13). Relative abundances of Ruminococcaceae, Clostridia, and Bacteroidia were all more sensitive predictors of response than Wargo type (54-57% vs 37%, respectively), showing that classification systems based on relative abundance could capture more responders than those based on Wargo type. Accordingly, the use of relative abundance can be used as an improved metric for identifying samples that are most associated with responders.

TABLE 13

Relative abundance of Ruminococcaceae, Clostridia, and Bacteroidia

were found to be the strongest predictors of response to checkpoint

therapy. Association of each microbiome characteristic analyzed with

response is shown below along with the statistical test used. Sensitivity

and specificity of each as a binary classifier is also shown; the

cut-off for binary classification is shown in parentheses after the

microbiome characteristic. OTUs were based on USEARCH and assigned

taxonomy as described. M-W U: Mann-Whitney U test.

Test for
Associ-

associ-
ation
Sensi-
Speci-

Microbiome
ation
with
tivity as
ficity as

Characteristic
with
response
binary
binary

(classifier cut-off)
response
(p-value)
classifier
classifier**

Wargo Types (I and II)
Fisher's
0.019*
37%
100%

Clostridia diversity
M-W U
0.024*
47%
92%

(≥and <90 16S OTUs)

Clostridia relative
M-W U
0.0032*
50%
100%

abundance

(≥and <32%)

Ruminococcaceae
M-W U
0.00026*
60%
100%

relative

abundance

(≥and <9.5%)

Bacteroidia
M-W U
0.0020*
50%
100%

relative

abundance

(≤and >57%)

*significant at p < 0.05 level

**the classifier threshold was set by first maximizing specificity (to 100% if possible) and then maximizing sensitivity

3. Phylogenetic Definition of Ruminococcaceae Improves Sensitivity to Detect Responders

Specific examination of taxa assigned to Ruminococcaceae by NCBI in the context of a phylogenetic tree derived from 16S rDNA sequences indicates that some taxa are misclassified with respect to Ruminococcaceae. FIG. 6 shows a phylogenetic tree of Ruminococcaceae derived from 16S rDNA sequences from NCBI RefSeq and sequenced strains from Seres' strain collection. Taxa in underlined were listed in the NCBI taxonomy as not belonging to Ruminococcaceae; accordingly, NCBI-based classification is clearly not consistent with phylogeny. Applicants therefore undertook the development of a definition of Ruminococcaceae that is more indicative of true evolutionary relationships using an internal phylogenetic-based classification system (specifically, clades 14, 61, 101, 125, 135). Clade 13, traditionally classified as Ruminococcaceae, was left out of the definition of Ruminococcaceae for purposes of analyzing responder and non-responder microbiomes because the clade was highly divergent from the rest of the Ruminococcaceae (FIG. 6). Clade-based relative abundance of Ruminococcaceae was significantly associated with response (p=0.00078, Mann-Whitney U test) and was more sensitive than the NCBI-based definition (67%) while maintaining 100% specificity (Table 14, FIG. 7). Further, the threshold was increased from 9.5% to 12% using the clade-based definition because a greater number of Ruminococcaceae species were detected by the clade-based definition, resulting in higher per sample abundances. Further studies therefore used the phylogenetic, clade-based definition of Ruminococcaceae.

TABLE 14

A clade-based definition of Ruminococcaceae is more sensitive in

classifying responders than an NCBI-based definition. Association

of each microbiome characteristic analyzed with response is shown

below along with the statistical test used. Sensitivity and specificity

of each a binary classifier is also shown; the cut-off for binary

classification is shown in parentheses after the microbiome characteristic.

OTUs were based on USEARCH and assigned taxonomy as described.

M-W U: Mann-Whitney U test.

Test for
Associ-

associ-
ation
Sensi-
Speci-

Microbiome
ation
with
tivity
ficity

Characteristic
with
response
as binary
as binary

(classifier cut-off)
response
(p-value)
classifier
classifier

Ruminococcaceae
M-W U
0.00026*
60%
100%

relative

abundance

(≥and <9.5%)

Ruminococcaceae clade-
M-W U
0.00078*
67%
100%

based relative abundance

(≥and <12%)

*significant at p < 0.05 level

4. Combination of Ruminococcaceae and Bacteroidia Provides Increased Sensitivity while Maintaining Specificity

An analysis was performed to determine if a combination of classification systems would provide superior sensitivity and specificity over a single classification system. The union of a number of relative abundance metrics listed above was examined for sensitivity and specificity in detecting responders from the total patient pool (Table 15). While most combinatorial metrics showed 100% specificity, combining a minimum Ruminococcaceae clade-based abundance with a maximum Bacteroidia clade-based abundance showed the highest sensitivity (80%). Details of where each sample fell within this distribution are shown in FIG. 8.

TABLE 15

Combination of Ruminococcaceae and Bacteroidia provides increased

sensitivity while maintaining specificity. Sensitivity and specificity

of combining classification systems is shown below.

Sensi-
Speci-

Classification System
tivity
ficity

Clostridia Relative Abundance (above 32%) OR
67%
100%

Ruminococcaceae Relative Abundance (above 9.5%)

Ruminococcaceae Relative Abundance (above 9.5%)
73%
92%

OR Bacteroidia Relative Abundance (below 57%)

Ruminococcaceae clade-based Relative Abundance
80%
100%

(above 12%) OR Bacteroidia Relative Abundance

(below 57%)

Clostridia Relative Abundance (above 32%) OR
60%
100%

Bacteroidia Relative Abundance (below 57%)

Clostridia Relative Abundance (above 32%) OR
73%
100%

Ruminococcaceae Relative Abundance (above 9.5%)

OR Bacteroidia Relative Abundance (below 57%)

5. Validation of Ruminococcaceae Metric in Second Cohort

Following development of the combined metric above, a new dataset was generated (n=69), using the same selection criteria for patients as Gopalakrishnan et al (2018) and it was desired to validate the metric using this new dataset. Relative abundance of clade-based Ruminococcaceae was significantly associated with response in the validation dataset (p=0.031, Table 16), while relative abundance of Bacteroidia was not (p=0.5, Table 15). De novo analysis to identify taxa at the (NCBI taxonomy-based) class and family level significantly associated with response identified only Ruminococcaceae and Clostridia (unadjusted p=0.047 and 0.049, respectively), indicating that no strong, conflicting signal existed in the validation dataset that was absent from the original, published dataset.

TABLE 16

Validation test of Ruminococcaceae and Bacteroidia relative abundances.

P-values listed include the original, published data from Gopalakrishnan

et al (2018) (n = 43), the validation cohort (n = 69),

and the combination of the two datasets (n = 112). All p-

values were generated with the Mann-Whitney U test.

Original
Validation
Combined

Measure
P-value
P-value
P-value

Ruminococcaceae clade-
0.00078*
0.031*
0.00012*

based relative

abundance

Bacteroidia relative
0.0020*
0.50
0.035*

abundance

*significant at p < 0.05 level

The 12% cutoff for clade-based Ruminococcaceae and the 57% cutoff for Bacteroidia discussed above were both further evaluated with respect to sensitivity and specificity. While specificity of 12% Ruminococcaceae decreased for both the validation and combined datasets, sensitivity remained in the 67-69% range (Table 17). Evaluation of the ROC curve for Ruminococcaceae did not suggest a significantly better cutoff than 12% existed in the combined dataset (FIG. 9). Patients with <12% Ruminococcaceae made up 47% (53/112) of total patients, but 72% of total non-responders. Patients with >=12% Ruminococcaceae, on the other hand, made up 53% of total patients and 68% of total responders (FIG. 10). For Bacteroidia, specificity dropped while sensitivity remained stable; however, sensitivity of Bacteroidia was near 50% in all datasets (Table 16), giving it little power to distinguish responders from non-responders when specificity was low. Based on these analyses, using a minimum 12% Ruminococcaceae clade-based abundance alone has the greatest combined specificity and sensitivity for distinguishing responders from non-responders in the combined dataset.

TABLE 17

Sensitivity and specificity of Ruminococcaceae and Bacteroidia thresholds in all datasets.

Datasets include the original, published data from Gopalakrishnan et al (2018) (n =

43), the validation cohort (n = 69), and the combination of the two datasets (n = 112).

Original
Original
Validation
Validation
Combined
Combined

Threshold
Sensitivity
Specificity
Sensitivity
Specificity
Sensitivity
Specificity

12% Ruminococcaceae
67%
100%
69%
60%
68%
73%

(clade-based)

57% Bacteroidia relative
50%
100%
54%
57%
52%
70%

abundance

* significant at p < 0.05 level

6. Ruminococcaceae Significantly Different Despite Classification of Stable Disease

It was also determined whether the signature held if patients with stable disease were excluded from the analysis. Ruminococcaceae clade-based relative abundance maintained an equivalently significant difference between responders and non-responders whether stable disease patients (and the two patients classified as responders but without a specific RECIST classification) were included as responders (p=0.0012, Mann-Whitney U test) or excluded from the analysis altogether (p=0.0010, Mann-Whitney U test). Further, exclusion of stable disease slightly increased sensitivity to detect responders in the combined dataset (68% with all patients to 74% excluding stable disease), while maintaining specificity (73% with all patients to 74% excluding stable disease). Examination of the ROC curve for the combined dataset excluding stable disease patients affirmed choice of the 12% cutoff for Ruminococcaceae (FIG. 11).

C. Summary & Conclusion

A number of recent studies have established a correlation between microbiome composition and response to checkpoint therapy for treatment of cancer. In particular, Gopalakrishnan et al (2018) found that responder microbiomes were enriched for Clostridiales and Ruminococcaceae, while non-responder microbiomes were enriched in Bacteroidales. They further subdivided patients into microbiome “types,” where the Type 1 cluster consisted solely of responders while Type 2 included a mix of responders and non-responders. The study herein sought to verify the findings of Gopalakrishnan et al (2018) and define a signature for the design of a microbiome therapeutic. The signature was validated with a new cohort of patients.

In conclusion, analysis of the validation dataset shows that responders were enriched in Ruminococcaceae, as defined herein, but non-responders were not enriched in Bacteroidia. Using a clade-based relative abundance (12%) of Ruminococcaceae alone achieved the greatest sensitivity and specificity in the validation and combined datasets. Exclusion of stable disease patients from the definition of responder did not reduce the significance of association between Ruminococcaceae and response or alter the 12% threshold. While the association between Ruminococcaceae and responders found in Gopalakrishnan et al (2018) was validated in this analysis, these results contrast with Gopalakrishnan et al (2018) in that non-responders were not found to be enriched in Bacteroidia.

The discoveries disclosed herein therefore demonstrate a method that can be used to identify mircobiomes associated with response to checkpoint inhibitor therapy. Accordingly, this analysis can be used in methods of identifying suitable donors for microbiome compositions to be used, e.g., as adjunct therapies for checkpoint inhibitor therapy or other cancer therapies. In addition to this discovery of a metric for identifying donors with useful GI microbiomes for therapeutic use, the discovery provides early identification of such donors, e.g., so that time and expense wasted on processing donations from unsuitable donors is greatly reduced.

All of the methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

XIII. Tables

Tables 1A-1B: Aggregate Rankings. Aggregate rankings after combining data from all analysis methods are shown. The species rankings are identified in both responder and non-responder patient groups.

TABLE 1A

Aggregate Ranked List - Responders

Species
Rank

Blautia_SC109
1

Parabacteroides distasonis

2

Bilophila_unclassified
3

Ruminococcus
_—
bicirculans_SC30
4

Subdoligranulum_unclassified
5

Blautia_SC102
6

Gemmiger
_—
formicilis_SC193
7

Ruminococcus
_—
albus

8

Bacteroides
_—
dorei

9

Bifidobacterium
_—
bifidum

10

Bifidobacterium
_—
longum

11

Fusicatenibacter
_—
saccharivorans_SC160
12

Eubacterium
_—
biforme

13

Roseburia
_—
faecis_SC53
14

Lachnospiraceae_bacterium_5_1_63FAA (Anaerostipes hadrus)
15

Gemmiger
_—
formicilis_SC141
16

Ruminococcus
_—
bromii

17

Alistipes
_—
senegalensis

18

Clostridium_SC178
19

Odoribacter
_—
splanchnicus

20

Faecalibacterium
_—
prausnitzii

21

Clostridium_SC64
22

Blautia
_—
wexlerae_SC15
23

Coprococcus
_—
catus

24

Clostridium_SC188
25

Streptococcus
_—
parasanguinis

26

Erysipelotrichaceae_bacterium_21_3
27

Barnesiella
_—
intestinihominis

28

Clostridium_SC26
29

Clostridium
_—
lavalense_SC43
30

Blautia
_—
faecis_SC4
31

Streptococcus
_—
australis

32

Collinsella
_—
aerofaciens

33

Clostridium_SC92
34

TABLE 1B

Aggregate Ranked List - Non-Responders

Species
Rank

Bacteroides
_—
thetaiotaomicron

1

Collinsella_unclassified
2

Ruminococcus
_—
torques

3

Bacteroides
_—
vulgatus

4

Anaerotruncus
_—
colihominis

5

Escherichia
_—
coli

6

Prevotella
_—
copri

7

Bacteroides
_—
massiliensis

8

Paraprevotella
_—
clara

9

Paraprevotella
_—
xylaniphila

10

Bacteroides
_—
xylanisolvens

11

Bacteroides
_—
coprocola

12

Ruminococcus
_—
gnavus

13

Bilophila
_—
wadsworthia

14

Parabacteroides
_—
merdae

15

Collinsella
_—
aerofaciens

16

Lachnospiraceae_bacterium_2_1_58FAA
17

Paraprevotella_unclassified
18

Klebsiella
_—
pneumoniae

19

Adlercreutzia
_—
equolifaciens

20

Escherichia_unclassified
21

Flavonifractor_SC129
22

Clostridium
_—
aldenense_SC114
23

Lachnospiraceae_bacterium_3_1_46FAA
24

Holdemania
_—
filiformis

25

Ruminococcaceae_bacterium_D16
26

Blautia
_—
faecis_SC4
27

Clostridium
_—
bolteae

28

Lachnospiraceae_bacterium_1_1_57FAA
29

Veillonella
_—
parvula

30

Lachnospiraceae_bacterium_7_1_58FAA
31

Veillonella_unclassified
32

Parabacteroides
_—
distasonis

33

Roseburia
_—
intestinalis

34

Bacteroides
_—
faecis

35

Dialister
_—
invisus

36

Eubacterium
_—
eligens

37

Tables 2A-2B. Differential Prevalence Rankings. Differential prevalence rankings are shown. The species are ranked among responder and non-responder patient groups.

TABLE 2A

Differential Prevalence - Responders

Species
Rank

Parabacteroides distasonis

1

Blautia_SC109
2

Blautia_SC102
3

Bacteroides
_—
dorei

4

TABLE 2B

Differential Prevalence - Non-Responders

Species
Rank

Anaerotruncus
_—
colihominis

1

Parabacteroides
_—
merdae

2

Tables 3A-3B. LDA Abundance Rankings. Linear Discriminant Analysis (LDA) abundance rankings are shown. The species are ranked among responder and non-responder patient groups.

TABLE 3A

LDA Abundance - Responders

Species
Rank

Ruminococcus
_—
bicirculans_SC30
1

Ruminococcus
_—
albus

2

Blautia_SC102
3

Gemmiger
_—
formicilis_SC141
4

Gemmiger
_—
formicilis_SC193
5

Clostridium_SC188
6

Subdoligranulum_unclassified
7

Clostridium
_—
lavalense_SC43
8

Blautia
_—
faecis_SC4
9

Streptococcus
_—
australis

10

Clostridium_SC92
11

Clostridium_sp_L2_50
12

Faecalibacterium
_—
prausnitzii

13

Eubacterium
_—
siraeum

14

Clostridium_SC125
15

Blautia_SC109
16

Ruminococcus
_—
bromii

17

Lachnospiraceae_bacterium_3_1_46FAA
18

Coprococcus
_—
comes

19

Erysipelotrichaceae_bacterium_21_3
20

Odoribacter
_—
laneus

21

Dorea
_—
longicatena

22

Pseudoflavonifractor
_—
capillosus_SC163
23

Eubacterium
_—
rectale

24

Lachnospiraceae_bacterium_3_1_57FAA_CT1
25

TABLE 3B

LDA Abundance - Non-Responders

Species
Rank

Bacteroides
_—
vulgatus

1

Bacteroides
_—
xylanisolvens

2

Lachnospiraceae_bacterium_2_1_58FAA
3

Ruminococcus
_—
gnavus

4

Prevotella
_—
copri

5

Tables 4A-4B. LASSO Prevalence Rankings. LASSO prevalence rankings are shown. The species are ranked among responder and non-responder patient groups.

TABLE 4A

Lasso Prevalence - Responders

Species
Rank

Parabacteroides distasonis

1

Blautia_SC109
2

Bacteroides
_—
dorei

3

Eubacterium
_—
biforme

4

Alistipes
_—
senegalensis

5

Clostridium_SC64
6

TABLE 4B

Lasso Prevalence - Non-Responders

Species
Rank

Collinsella_unclassified
1

Bacteroides
_—
coprocola

2

Anaerotruncus
_—
colihominis

3

Bacteroides
_—
massiliensis

4

Adlercreutzia
_—
equolifaciens

5

Tables 5A-5B. LASSO Abundance Rankings. LASSO abundance rankings are shown. The species are ranked among responder and non-responder patient groups.

TABLE 5A

Lasso Abundance - Responders

Species
Rank

Blautia_SC109
1

Parabacteroides distasonis

2

Bifidobacterium
_—
bifidum

3

Subdoligranulum_unclassified
4

TABLE 5B

Lasso Abundance - Non-Responders

Species
Rank

Bacteroides
_—
thetaiotaomicron

1

Paraprevotella
_—
clara

2

Bacteroides
_—
massiliensis

3

Tables 6A-6B. Random Forest Prevalence Rankings. Random Forest prevalence rankings are shown. The species are ranked among responder and non-responder patient groups.

TABLE 6A

Random Forest Prevalence - Responders

Species
Rank

Blautia_SC109
1

Parabacteroides distasonis

2

Bifidobacterium
_—
longum

3

Blautia_SC102
4

Erysipelotrichaceae_bacterium_21_3
5

Bifidobacterium
_—
bifidum

6

Odoribacter
_—
splanchnicus

7

Barnesiella
_—
intestinihominis

8

TABLE 6B

Random Forest Prevalence - Non-Responders

Species
Rank

Escherichia
_—
coli

1

Bacteroides
_—
thetaiotaomicron

2

Collinsella
_—
aerofaciens

3

Bacteroides
_—
coprocola

4

Klebsiella
_—
pneumoniae

5

Parabacteroides
_—
merdae

6

Clostridium
_—
aldenense_SC114
7

Bacteroides
_—
massiliensis

8

Ruminococcaceae_bacterium_D16
9

Tables 7A-7B. Random Forest Abundance Rankings. Random Forest abundance rankings are shown. The species are ranked among responder and non-responder patient groups.

TABLE 7A

Random Forest Abundance - Responders

Species
Rank

Bilophila_unclassified
1

Ruminococcus
_—
bromii

2

Gemmiger
_—
formicilis_SC193
3

Roseburia
_—
faecis_SC53
4

Clostridium_SC178
5

Blautia
_—
wexlerae_SC15
6

Streptococcus
_—
parasanguinis

7

Bifidobacterium
_—
longum

8

Odoribacter
_—
splanchnicus

9

Blautia_SC109
10

Collinsella
_—
aerofaciens

11

Fusicatenibacter
_—
saccharivorans_SC160
12

Eubacterium
_—
eligens

13

TABLE 7B

Random Forest Abundance - Non-Responders

Species
Rank

Ruminococcus
_—
torques

1

Paraprevotella
_—
xylaniphila

2

Bacteroides
_—
thetaiotaomicron

3

Paraprevotella_unclassified
4

Bilophila
_—
wadsworthia

5

Ruminococcus
_—
gnavus

6

Flavonifractor_SC129
7

Lachnospiraceae_bacterium_3_1_46FAA
8

Bacteroides
_—
massiliensis

9

Clostridium
_—
bolteae

10

Lachnospiraceae_bacterium_1_1_57FAA
11

Tables 8A-8B. Random Forest abunQ Rankings. Random Forest abunQ rankings are shown. The species are ranked among responder and non-responder patient groups.

TABLE 8A

Random Forest abunQ - Responders

Species
Rank

Subdoligranulum_unclassified
1

Fusicatenibacter
_—
saccharivorans_SC160
2

Gemmiger
_—
formicilis_SC193
3

Lachnospiraceae_bacterium_5_1_63FAA
4

Faecalibacterium
_—
prausnitzii

5

Coprococcus
_—
catus

6

Blautia_SC109
7

Clostridium_SC26
8

TABLE 8B

Random Forest abunQ - Non-Responders

Species
Rank

Prevotella
_—
copri

1

Bilophila
_—
wadsworthia

2

Ruminococcus
_—
gnavus

3

Escherichia
_—
coli

4

Escherichia_unclassified
5

Anaerotruncus
_—
colihominis

6

Bacteroides
_—
thetaiotaomicron

7

Holdemania
_—
filiformis

8

Klebsiella
_—
pneumoniae

9

Blautia
_—
faecis_SC4
10

Veillonella
_—
parvula

11

Lachnospiraceae_bacterium_7_1_58FAA
12

Veillonella_unclassified
13

Parabacteroides
_—
distasonis

14

Roseburia
_—
intestinalis

15

Bacteroides
_—
faecis

16

Dialister
_—
invisus

17

Eubacterium
_—
eligens

18

Clostridium
_—
bolteae

19

Table 9. Data Types and Analysis Methods. The three data types and four analysis methods applied to each type of data is shown. Analysis methods applied to a specific data type is marked with an “X”.

TABLE 9

Data type

Quantile

normalized

Method
Prevalence
Abundance
abundance

Fisher's exact test
X
—
—

Lasso regression
X
X
X

Random forest
X
X
X

Linear discriminant
—
X
—

analysis

Table 10. Species Call Information. Species calls for bacteria identified in the examples are provided. Bacteria were identified by percent identity to known full length 16S rDNA sequences.

“PCT ID” refers to the percent identity of a 16S rDNA sequence of the species identified to the 16S rDNA sequence of the associated NCBI call (NR Lookup). “Scientific Name” refers to the NCBI name associated with the sequence.

TABLE 10

Species
PCT ID
NR Lookup
Scientific Name

Parabacteroides_unclassified
98.9
NR_074376

Parabacteroides distasonis

Parabacteroides_unclassified
98.7
NR_041342

Parabacteroides distasonis

Bifidobacterium
_—
bifidum

99.9
NR_118793

Bifidobacterium bifidum

Bifidobacterium
_—
bifidum

99.9
NR_044771

Bifidobacterium bifidum

Bifidobacterium
_—
bifidum

99.9
NR_117505

Bifidobacterium bifidum

Bifidobacterium
_—
bifidum

99.9
NR_113873

Bifidobacterium bifidum

Subdoligranulum_unclassified
99.3
NR_104846

Gemmiger formicilis

Subdoligranulum_unclassified
99.3
NR_028997

Subdoligranulum variabile

Bacteroides
_—
dorei

99.9
NR_041351

Bacteroides dorei

Bacteroides
_—
dorei

97.2
NR_074515

Bacteroides vulgatus

Bacteroides
_—
dorei

97.4
NR_112946

Bacteroides vulgatus

Eubacterium
_—
biforme

99.1
NR_044731

Holdemanella biformis

Alistipes
_—
senegalensis

100
NR_118219

Alistipes senegalensis JC50

Fusicatenibacter
_—
saccharivorans_SC160
99.6
NR_114326

Fusicatenibacter saccharivorans

Lachnospiraceae_bacterium_5_1_63FAA
99.9
NR_117138

Anaerostipes hadrus

Lachnospiraceae_bacterium_5_1_63FAA
99.8
NR_117139

Anaerostipes hadrus

Lachnospiraceae_bacterium_5_1_63FAA
99
NR_104799

Anaerostipes hadrus

Faecalibacterium
_—
prausnitzii

98
NR_028961

Faecalibacterium prausnitzii

Coprococcus
_—
catus

98.1
NR_024750

Coprococcus catus

Clostridium_SC26
98.4
NR_151982

Agathobaculum butyriciproducens

Clostridium_SC26
98.3
NR_152060

Butyricicoccus faecihominis

Bifidobacterium
_—
longum

100
NR_043437

Bifidobacterium longum subsp.

infantis

Bifidobacterium
_—
longum

99.5
NR_145535

Bifidobacterium longum subsp.

suillum

Bifidobacterium
_—
longum

99.1
NR_117506

Bifidobacterium longum

Bifidobacterium
_—
longum

97.6
NR_040783

Bifidobacterium breve

Bifidobacterium
_—
longum

98
NR_044691

Bifidobacterium longum

Bifidobacterium
_—
longum

97.5
NR_044693

Bifidobacterium longum subsp. suis

Erysipelotrichaceae_bacterium_21_3
98.3
NR_029164

Clostridium innocuum

Odoribacter
_—
splanchnicus

100
NR_074535

Odoribacter splanchnicus

Odoribacter
_—
splanchnicus

99.9
NR_113075

Odoribacter splanchnicus

Odoribacter
_—
splanchnicus

99
NR_044636

Odoribacter splanchnicus

Barnesiella
_—
intestinihominis

100
NR_041668

Barnesiella intestinihominis YIT 11860

Barnesiella
_—
intestinihominis

100
NR_113073

Barnesiella intestinihominis

Table 11: Species Call Information. Species calls are provided for bacteria belonging to one or more species that are phylogenetic descendants of the MRCA of Faecalibacterium prausnitzii and Flavonifractor plautii. “Assigned Name” refers to the NCBI name associated with the sequence. Full length 16S rDNA sequences are listed for each species identified.

TABLE 11

Identifier
Assigned Name
16S Sequence

GCF_000154325

Eubacterium siraeum
CAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAAG

TCGAACGGTGAAGAGGAGCTTGCTCCTCGGATCAGTGGCGGACGGGTGAGTAACACG

TGAGCAACCTGGCTCTAAGAGGGGGACAACAGTTGGAAACGACTGCTAATACCGCAT

AACGTATCGGGATGGCATCTTCCTGATACCAAAGATTTTATCGCTTAGAGATGGGCTC

GCGTCTGATTAGATAGTTGGCGGGGTAACGGCCCACCAAGTCGACGATCAGTAGCCG

GACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGA

GGCAGCAGTGGGGGATATTGGACAATGGGGGCAACCCTGATCCAGCGACGCCGCGTG

AGGGAAGAAGGTTTTCGGATTGTAAACCTCTGTTGACGGAGNNNNNNNTGATGGTAT

CCGTTTAGAAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGC

AAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGTGTAGGCGGGATATCAAGTCAGA

AGTGAAAATTACGGGCTCAACTCGTAACCTGCTTTTGAAACTGACATTCTTGAGTGAA

GTAGAGGCAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAAC

ACCAGTGGCGAAGGCGGCTTGCTGGGCTTTTACTGACGCTGAGGCTCGAAAGCGTGG

GGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTACTAGGT

GTGGGGGGATTGACCCCTTCCGTGCCGGAGTAAACACAATAAGTAATCCACCTGGGG

AGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTG

GAGTATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAGGTCTTGACATCGAGT

GACCGCCTAAGAGATTAGGCTTTCCCTTCGGGGACACAAAGACAGGTGGTGCATGGT

TGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTA

TCATTAGTTGCTACGCAAGAGCACTCTAATGAGACTGCCGTTGACAAAACGGAGGAA

GGTGGGGATGACGTCAAATCATCATGCCCTTTATGACCTGGGCTACACACGTACTACA

ATGGCGTTTAACAAAGAGAAGCAAAGCCGCGAGGCAGAGCAAATCTCCAAAAAACG

TCTCAGTTCGGATTGTAGGCTGCAACTCGCCTACATGAAGTCGGAATTGCTAGTAATC

GTAGGTCAGCATACTACGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAA

CCATGAGAGTTGGCAACACCCGAAGTCGGTAGTCTAACCGCAAGGAGGACGCCGCCG

AAGGTGGGGTTGATGATTAGGGTTAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGC

GGCTGGATCACCTCCTTT (SEQ ID NO: 108)

GCF_000154345

Clostridium leptum
TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

AGTCGAACGGAGTTAAATTCGACACCCGAGTATCCGGCCGGGAGGCGGGGTGCTGGG

GGTTGGATTTAACTTAGTGGCGGACGGGTGAGTAACGCGTGAGTAACCTGCCTTTCAG

AGGGGGATAACGTTCTGAAAAGAACGCTAATACCGCATAACATCAATTTATCGCATG

ATAGGTTGATCAAAGGAGCAATCCGCTGGAAGATGGACTCGCGTCCGATTAGCCAGT

TGGCGGGGTAACGGCCCACCAAAGCGACGATCGGTAGCCGGACTGAGAGGTTGAAC

GGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGAT

ATTGCACAATGGGGGAAACCCTGATGCAGCAACGCCGCGTGAGGGAAGAAGGTTTTC

GGATTGTAAACCTCTGTTCTTAGTGACGATAATGACGGTAGCTAAGGAGAAAGCTCC

GGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGAGCGAGCGTTGTCCGGATT

TACTGGGTGTAAAGGGTGCGTAGGCGGCGAGGCAAGTCAGGCGTGAAATCTATGGGC

TTAACCCATAAACTGCGCTTGAAACTGTCTTGCTTGAGTGAAGTAGAGGTAGGCGGA

ATTCCCGGTGTAGCGGTGAAATGCGTAGAGATCGGGAGGAACACCAGTGGCGAAGGC

GGCCTACTGGGCTTTAACTGACGCTGAAGCACGAAAGCATGGGTAGCAAACAGGATT

AGATACCCTGGTAGTCCATGCCGTAAACGATGATTACTAGGTGTGGGGGGTCTGACC

CCCTCCGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGG

TTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAAT

TCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCGTCTAACGAAGCAGAGAT

GCATTAGGTGCCCTTCGGGGAAAGGCGAGACAGGTGGTGCATGGTTGTCGTCAGCTC

GTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTTTCTAGTTGCT

ACGCAAGAGCACTCTAGAGAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGA

CGTCAAATCATCATGCCCCTTATGACCTGGGCCACACACGTACTACAATGGCTGTAAA

CAGAGGGAAGCAAAGCCGCGAGGTGGAGCAAAACCCTAAAAGCAGTCCCAGTTCGG

ATCGCAGGCTGCAACCCGCCTGCGTGAAGTCGGAATTGCTAGTAATCGCGGATCAGC

ATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGGGAG

CCGGTAATACCCGAAGCCAGTAGTTCAACCGCAAGGAGAGCGCTGTCGAAGGTAGGA

TTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATC

ACCTCCTTT (SEQ ID NO: 109)

GCF_000154565

Anaerotruncus

CAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAAG

colihominis

TCGAACGGAGCTTACGTTTTGAAGTTTTCGGATGGATGAATGTAAGCTTAGTGGCGGA

CGGGTGAGTAACACGTGAGCAACCTGCCTTTCAGAGGGGGATAACAGCCGGAAACGG

CTGCTAATACCGCATGATGTTGCGGGGGCACATGCCCCTGCAACCAAAGGAGCAATC

CGCTGAAAGATGGGCTCGCGTCCGATTAGCCAGTTGGCGGGGTAACGGCCCACCAAA

GCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGGCGAAAGCCTGA

TGCAGCGACGCCGCGTGAGGGAAGACGGTCTTCGGATTGTAAACCTCTGTCTTTGGG

GAAGAAAATGACGGTACCCAAAGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCG

CGGTAATACGTAGGGAGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAG

GCGGGATGGCAAGTAGAATGTTAAATCCATCGGCTCAACCGGTGGCTGCGTTCTAAA

CTGCCGTTCTTGAGTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGC

GTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACGC

TGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGT

AAACGATGATTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAA

TAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGG

GGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTAC

CAGGTCTTGACATCGGATGCATAGCCTAGAGATAGGTGAAGCCCTTCGGGGCATCCA

GACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGC

AACGAGCGCAACCCTTATTATTAGTTGCTACGCAAGAGCACTCTAATGAGACTGCCGT

TGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGG

GCTACACACGTACTACAATGGCACTAAAACAGAGGGCGGCGACACCGCGAGGTGAA

GCGAATCCCGAAAAAGTGTCTCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATGAA

GTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTT

GTACACACCGCCCGTCACACCATGGGAGTCGGTAACACCCGAAGCCAGTAGCCTAAC

CGCAAGGGGGGCGCTGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAG

GTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 110)

GCF_000157955

Subdoligranulum

NAAGAAGGTTTTCGGATTGTAAACTCCTGTCGTTAGGGACGAATCTTGACGGTACCTA

variabile

ACAAGAAAGCACCGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGGTGCAA

GCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGACCGGCAAGTTGGAAG

TGAAATCTATGGGCTCAACCCATAAATTGCTTTCAAAACTGCTGGCCTTGAGTAGTGC

AGAGGTAGGTGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGGGAGGAACAC

CAGTGGCGAAGGCGACCTACTGGGCACCAACTGACGCTGAGGCTCGAAAGCATGGGT

AGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGATTACTAGGTGT

TGGAGGATTGACCCCTTCAGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAG

TACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGA

GTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCGATGC

ATAGTGCAGAGATGCATGAAGTCCTTCGGGACATCGAGACAGGTGGTGCATGGTTGT

CGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATTG

CCAGTTACTACGCAAGAGGACTCTGGCGAGACTGCCGTTGACAAAACGGAGGAAGGT

GGGGATGACGTCAAATCATCATGCCCTTTATGACCTGGGCTACACACGTACTACAATG

GCGTTTAACAAAGAGATGCAAGACCGCGAGGTGGAGCAAAACTCAAAAACAACGTC

TCAGTTCAGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATTGCTAGTAATCGC

GGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACC

ATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAGGACGCCGCCGA

AGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCG

GCTGGATCACCTCCTTT (SEQ ID NO: 111)

GCF_000158655

Clostridium

ATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

methylpentosum

GTCGAACGGAGTTGTTTTGGAGAAGCCCTTCGGGGTGGAACTGATTCAACTTAGTGGC

GGACGGGTGAGTAACACGTGAGCAACCTGCCTTACAGAGGGGAATAACGTTTGGAAA

CGAACGCTAATACCGCATAACATAACGGAATCGCATGGTTTTGTTATCAAAGATTATA

TCGCTGTAAGATGGGCTCGCGTCTGATTAGATAGTTGGTGAGGTAATGGCTCACCAAG

TCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGA

TGCAGCGACGCCGCGTGAAGGAAGAAGGCCTTCGGGTTGTAAACTTCTGTCTTCAGG

GACGATAATGACGGTACCTGAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGC

GGTAATACGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGG

CGGGATTGCAAGTTGAATGTGAAATCTATGGGCTTAACCCATAAACTGCGTTCAAAA

CTGCAGTTCTTGAGTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGC

GTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACGC

TGAGGCTCGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGT

AAACGATGATTACTAGGTGTAGGGGGGTCAACCTTCTGTGCCGGAGTTAACACAATA

AGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGG

CCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCA

GGTCTTGACATCCAACTAACGAAGTAGAGATACATTAGGTGCCCTTCGGGGAAAGTT

GAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCC

GCAACGAGCGCAACCCTTACATTTAGTTGCTACGCAAGAGCACTCTAGATGGACTGC

CGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACC

TGGGCTACACACGTACTACAATGGCTATTAACAGAGGGAAGCAAAACAGTGATGTGG

AGCAAACCCCTAAAAATAGTCTCAGTTCGGATTGTAGGCTGCAACTCGCCTACATGA

AGCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCC

TTGTACACACCGCCCGTCACACCATGAGAGTTGGCAACACCCGAAGTCAGTAGTCTA

ACCGCAAGGAGGACGCTGCCGAAGGTGGGGTTGATGATTAGGGTGAAGTCGTAACAA

GGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 5)

GCF_000169255

Pseudoflavonifractor

TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

capillosus

GTCGAACGGAGAGCTCATGACAGAGGATTCGTCCAATGGATTGGGTTTCTTAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTCGGAGTGGGGAATAACAGTCCGAA

AGGACTGCTAATACCGCATAATGCAGCTGAGTCGCATGACACTGGCTGCCAAAGATT

TATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTAGTTGGCGGGGTAACGGCCCACCA

AGGCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTGAGACAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCT

GACCCAGCAACGCCGCGTGAAGGATGAAGGCTTTCGGGTTGTAAACTTCTTTTATCAG

GGACGAAATAAATGACGGTACCTGATGAATAAGCCACGGCTAACTACGTGCCAGCAG

CCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTG

TAGGCGGGACTGCAAGTCAGGTGTGAAAACCACGGGCTCAACCTGTGGCCTGCATTT

GAAACTGTAGTTCTTGAGTGCTGGAGAGGCAATCGGAATTCCGTGTGTAGCGGTGAA

ATGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACAGTAACTG

ACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACG

CCGTAAACGATGGATACTAGGTGTGGGGGGACTGACCCCCTCCGTGCCGCAGTTAAC

ACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGA

CGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACC

TTACCAGGGCTTGACATCCGACTAACGAAGCAGAGATGCATTAGGTGCCCTTCGGGG

AAAGTCGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTA

AGTCCCGCAACGAGCGCAACCCTTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGA

GACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTT

ATGTCCTGGGCCACACACGTACTACAATGGTGGTTAACAGAGGGAAGCAATGCCGCG

AGGTGGAGCAAATCCCTAAAAGCCATCCCAGTTCGGATTGCAGGCTGAAACCCGCCT

GTATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCC

CGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGT

AGCCTAACCGCAAGGAGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCG

TAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 6)

GCF_000178115

Ethanoligenens

TTGGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

harbinense

GTCGAGCGGAGTCCTTCGGGACTTAGCGGCGGACGGGTGAGTAACGCGTGAGCAACC

TGGCCTTCAGAGGGGGATAACGTCTGGAAACGGACGCTAATACCGCATGACATGGCG

GAGTCGCATGGCTCTGCCATCAAAGGAGTAATCCGCTGAGGGATGGGCTCGCGTCCG

ATTAGGTAGTTGGTGAGGTAACGGCTCACCAAGCCCGCGATCGGTAGCCGGACTGAG

AGGTTGGCCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCA

GTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCGACGCCGCGTGAGGGAA

GAAGGTCTTCGGATTGTAAACCTCTGTCTTTGGGGACGAATCAATGACGGTACCCAAG

GAGGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCG

TTGTCCGGAATTACTGGGTGTAAAGGGTGCGCAGGCGGGGCGGCAAGTTGGATGTGA

AAACTCCGGGCTCAACCCGGAGCCTGCATTCAAAACTGTCGCTCTTGAGTGAAGTAG

AGGCAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGATATCGGGAGGAACACCA

GTGGCGAAGGCGGCCTGCTGGGCTTTTACTGACGCTGAGGCACGAAAGCATGGGTAG

CAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGATTGCTAGGTGTGG

GGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAATAAGCAATCCACCTGGGGAGTA

CGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGT

ATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCACCGAAT

CCCCCAGAGATGGGGGAGTGCCCTTCGGGGAGCGGTGAGACAGGTGGTGCATGGTTG

TCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTG

AATAGTTGCTACGAAAGAGCACTCTATTCAGACCGCCGTTGACAAAACGGAGGAAGG

TGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTACTACAAT

GGCCATCAACAGAGGGAAGCAAGGCCGCGAGGTGGAGCGAACCCCTAAAAATGGTC

TCAGTTCAGATTGCAGGCTGAAACCCGCCTGCATGAAGATGGAATTGCTAGTAATCG

CGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACAC

CATGAGAGCCGGGGACACCCGAAGTCGGTTGGGTAACCGTAAGGAGCCCGCCGCCGA

AGGTGGAATCGGTAATTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCG

GCTGGATCACCTCCTTT (SEQ ID NO: 7)

GCF_000179635

Ruminococcus albus
TATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCTTAACACATGCA

AGTCGAACGAGCGAAAGAGTGCTTGCACTCTCTAGCTAGTGGCGGACGGGTGAGTAA

CACGTGAGCAATCTGCCTTTCGGAGAGGGATACCAATTGGAAACGATTGTTAATACCT

CATAACATAACGAAGCCGCATGACTTTGTTATCAAATGAATTTCGCCGAAAGATGAG

CTCGCGTCTGATTAGGTAGTTGGTGAGGTAACGGCCCACCAAGCCGACGATCAGTAG

CCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACG

GGAGGCAGCAGTGGGGAATATTGCACAATGGGCGAAAGCCTGATGCAGCGATGCCG

CGTGAGGGAAGAAGGTTTTAGGATTGTAAACCTCTGTCTTTGGGGACGATAATGACG

GTACCCAAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGG

GAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGATTGCAAGT

CAGGTGTGAAATTTAGGGGCTTAACCCCTGAACTGCACTTGAAACTGTAGTTCTTGAG

TGAAGTAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAG

GAACATCAGTGGCGAAGGCGGCTTACTGGGCTTTAACTGACGCTGAGGCTCGAAAGC

GTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTACT

AGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCT

GGGGAGTACGGCCGCAAGGCTGAAACTCAAAGGAATTGACGGGGACCCGCACAAGC

AGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACAT

CGTACGCATAGCATAGAGATATGTGAAATCCCTTCGGGGACGTATAGACAGGTGGTG

CATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGGTTAAGTCCCGCAACGAGCGCA

ACCCTTACTGTTAGTTGCTACGCAAGAGCACTCTAGCAGGACTGCCGTTGACAAAACG

GAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACG

TACTACAATGGCTGTTAACAGAGGGAAGCAAAACAGTGATGTGGAGCAAAACCCTAA

AAGCAGTCTTAGTTCGGATTGTAGGCTGCAACCCGCCTACATGAAGTCGGAATTGCTA

GTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCC

GTCACGCCATGGGAGTCGGTAACACCCGAAGCCTGTGTTCTAACCGCAAGGAGGAAG

CAGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGA

AGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 8)

GCF_000210095

Ruminococcus

TATGAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCCTAACACATGCA

champanellensis

AGTCGAACGGAGATAAAGACTTCGGTTTTTATCTTAGTGGCGGACGGGTGAGTAACA

CGTGAGCAACCTGCCTCTGAGAGAGGGATAGCTTCTGGAAACGGATGGTAATACCTC

ATAACATAGCGGTACCGCATGATACTGCTATCAAAGATTTATCGCTCAGAGATGGGCT

CGCGTCTGATTAGCTAGATGGTGAGGTAACGGCTCACCATGGCGACGATCAGTAGCC

GGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGG

AGGCAGCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAGCGATGCCGCGT

GGAGGAAGAAGGTTTTCGGATTGTAAACTCCTGTCTTAAGGGACGATAATGACGGTA

CCTTAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGAG

CGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGATTGCAAGTCAG

ATGTGAAAACTATGGGCTTAACCCATAGACTGCATTTGAAACTGTAGTTCTTGAGTGA

AGTAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAA

CATCGGTGGCGAAGGCGGCTTACTGGGCTTTTACTGACGCTGAGGCTCGAAAGCGTG

GGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGATTACTAGG

TGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCTGGG

GAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGT

GGAGTATGTGGTTTAATTCGAAGCAACGCGAAAAACCTTACCAGGTCTTGACATCGA

GTGAATGATCTAGAGATAGATCAGTCCTTCGGGACACAAAGACAGGTGGTGCATGGT

TGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTA

CCTTTAGTTGCTACGCAAGAGCACTCTAGAGGGACTGCCGTTGACAAAACGGAGGAA

GGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTACTACA

ATGGCAATGAACAGAGGGAAGCAATACAGTGATGTGGAGCAAATCCCCAAAAATTGT

CCCAGTTCAGATTGTAGGCTGCAACTCGCCTACATGAAGTCGGAATTGCTAGTAATCG

CAGATCAGCATGCTGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACAC

CATGGGAGTCGGTAACACCCGAAGCCAGTAGCCTAACCGCAAGGAGGGCGCTGTCGA

AGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCG

GCTGGATCACCTCCTTT (SEQ ID NO: 9)

GCF_000239295

Flavonifractor plautii
TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

GTCGAACGGGGTGCTCATGACGGAGGATTCGTCCAATGGATTGAGTTACCTAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTTGGAGAGGGGAATAACACTCCGAA

AGGAGTGCTAATACCGCATGAAGCAGTTGGGTCGCATGGCTCTGACTGCCAAAGATT

TATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTAGTAGGCGGGGTAACGGCCCACCT

AGGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGACAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCT

GACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTGTCG

GGGACGAAACAAATGACGGTACCCGACGAATAAGCCACGGCTAACTACGTGCCAGC

AGCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCG

TGTAGGCGGGATTGCAAGTCAGATGTGAAAACTGGGGGCTCAACCTCCAGCCTGCAT

TTGAAACTGTAGTTCTTGAGTGCTGGAGAGGCAATCGGAATTCCGTGTGTAGCGGTGA

AATGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACAGTAACT

GACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCAC

GCCGTAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGCAGTTAA

CACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTG

ACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAAC

CTTACCAGGGCTTGACATCCCACTAACGAGGCAGAGATGCGTTAGGTGCCCTTCGGG

GAAAGTGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTT

AAGTCCCGCAACGAGCGCAACCCTTATTGTTAGTTGCTACGCAAGAGCACTCTAGCG

AGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCT

TATGTCCTGGGCCACACACGTACTACAATGGTGGTTAACAGAGGGAGGCAATACCGC

GAGGTGGAGCAAATCCCTAAAAGCCATCCCAGTTCGGATTGCAGGCTGAAACCCGCC

TGTATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCC

CGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGT

AGCCTAACCGCAAGGAGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCG

TAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 10)

GCF_000283575

Oscillibacter

TATAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCTTAACACATGCA

valericigenes

AGTCGAACGGAGCACCCTTGATTGAGGTTTCGGCCAAATGAGAGGAATGCTTAGTGG

CGGACTGGTGAGTAACGCGTGAGGAACCTGCCTTTCAGAGGGGGACAACAGTTGGAA

ACGACTGCTAATACCGCATGATACATTTGGGCGACATCGCTTGAATGTCAAAGATTTA

TCGCTGAAAGATGGCCTCGCGTCTGATTAGATAGTTGGTGAGGTAACGGCCCACCAA

GTCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGATACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGACGCAAGTCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTAAGGG

GGAAGAGTAGAAGACGGTACCCCTTGAATAAGCCACGGCTAACTACGTGCCAGCAGC

CGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGTGT

AGCCGGGAAGGTAAGTCAGATGTGAAATCTGGGGGCTCAACCTCCAAACTGCATTTG

AAACTACTTTTCTTGAGTATCGGAGAGGTAATCGGAATTCCTTGTGTAGCGGTGAAAT

GCGTAGATATAAGGAAGAACACCAGTGGCGAAGGCGGATTACTGGACGACAACTGA

CGGTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGC

TGTAAACGATCAATACTAGGTGTGCGGGGACTGACCCCCTGCGTGCCGCAGTTAACA

CAATAAGTATTGCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGAC

GGGGGCCCGCACAAGCGGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAGAACCT

TACCAGGACTTGACATCCTACTAACGAGGTAGAGATACGTCAGGTGCCCTTCGGGGA

AAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAA

GTCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAG

ACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTA

TGTCCTGGGCTACACACGTAATACAATGGCGGTCAACAGAGGGATGCAAAGCCGTGA

GGTGGAGCGAACCCCTAAAAGCCGTCTCAGTTCGGATCGCAGGCTGCAACTCGCCTG

CGTGAAGTCGGAATCGCTAGTAATCGCGGATCAGAATGCCGCGGTGAATACGTTCCC

GGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTA

GCCTAACAGCAATGAGGGCGCGGCCGAAGGTGGGTTTGATAATTGGGGTGAAGTCGT

AACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 11)

GCF_000307265

Oscillibacter

TATAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCTTAACACATGCA

ruminantium

AGTCGAACGGAACACCCTTGACAGAGGTTTCGGCCAATGAAGAGGAATGTTTAGTGG

CGGACTGGTGAGTAACGCGTGAGGAACCTGCCTTTCAGAGGGGGACAACAGTTGGAA

ACGACTGCTAATACCGCATGAAGCAGCGAGGGGACATCCCCTTGCTGTCAAAGATTT

ATCGCTGAAAGATGGCCTCGCGTCTGATTAGCTAGTTGGTGGGGTAACGGCCCACCA

AGGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGATAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGACGCAAGTCT

GACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTAACA

GGGAAGAGAAGAAGACGGTACCTGTTGAATAAGCCACGGCTAACTACGTGCCAGCA

GCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGT

GTAGCCGGGAAGGCAAGTCAGATGTGAAATCTGGAGGCTCAACCTCCAAACTGCATT

TGAAACTGCTTTTCTTGAGTATCGGAGAGGTAATCGGAATTCCTTGTGTAGCGGTGAA

ATGCGTAGATATAAGGAAGAACACCAGTGGCGAAGGCGGATTACTGGACGACAACT

GACGGTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCA

CGCTGTAAACGATCAATACTAGGTGTGCGGGGACTGACCCCCTGCGTGCCGCAGTTA

ACACAATAAGTATTGCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATT

GACGGGGGCCCGCACAAGCGGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAGAA

CCTTACCAGGACTTGACATCCTACTAACGAGGTAGAGATACGTCAGGTGCCCTTCGGG

GAAAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTT

AAGTCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACTCTAGCG

AGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCT

TATGTCCTGGGCTACACACGTAATACAATGGCGGTCAACAGAGGGATGCAAAGCCGT

GAGGCAGAGCGAACCCCTAAAAGCCGTCTCAGTTCGGATCGTAGGCTGCAACTCGCC

TACGTGAAGTCGGAATCGCTAGTAATCGCGGATCAGAATGCCGCGGTGAATACGTTC

CCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGCCCG

TAGCCTAACTGCAAAGAGGGCGCGGTCGAAGGTGGGTTCGATAATTGGGGTGAAGTC

GTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 12)

GCF_000383295

Clostridium

CAAAGGAGCAATCCGCTGAAAGATGGACTCGCGTCCGATTAGCCAGTTGGCGGGGTA

sporosphaeroides

AAGGCCCACCAAAGCGACGATCGGTAGCCGGGTTGAGAGACTGAACGGCCACATTGG

GACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATG

GAGGAAACTCTGATGCAGCAATGCCGCGTGAGGGAAGACGGTCTTCGGATTGTAAAC

CTCTGTCCTTGGTGAAGATAATGACGGTAGCCAAGGAGGAAGCTCCGGCTAACTACG

TGCCAGCAGCCGCGGTAATACGTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTA

AAGGGTGCGTAGGCGGCTCTTTAAGTCGGGCGTGAAAGCTGTGGGCTTAACCCACAA

ATTGCGTTCGAAACTGGAGGGCTTGAGTGAAGTAGAGGTAGGCGGAATTCCCGGTGT

AGCGGTGAAATGCGTAGAGATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGG

GCTTTAACTGACGCTGAGGCACGAAAGCATGGGTAGCAAACAGGATTAGATACCCTG

GTAGTCCATGCCGTAAACGATGATTACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCC

GGAGTTAACACAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAA

AGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACG

CGAAGAACCTTACCAGGTCTTGACATCCAACTAACGAGGCAGAGATGCATTAGGTGC

CCTTCGGGGAAAGTTGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGAT

GTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTGATTAGTTGCTACGCAAGAGCA

CTCTAATCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATC

ATGCCCCTTATGACCTGGGCTACACACGTACTACAATGGTCGCCAACAGAGGGAAGC

CA (SEQ ID NO: 13)

GCF_000468015

Ruminococcus

TAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCTTAACACATGCAAG

callidus

TCGAACGGAGAACATTGAGCTTGCTTAATGTTCTTAGTGGCGGACGGGTGAGTAACA

CGTGAGTAACCTGCCTCTGAGAGTGGGATAGCTTCTGGAAACGGATGGTAATACCGC

ATAACATCATGGATTCGCATGTTTCTGTGATCAAAGATTTATCGCTTAGAGATGGACT

CGCGTCTGATTAGCTAGTTGGTAAGGTAACGGCTTACCAAGGCGACGATCAGTAGCC

GGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGG

AGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGATGCCGCGT

GGAGGAAGAAGGTTTTCGGATTGTAAACTCCTGTTGAAGAGGACGATAATGACGGTA

CTCTTTTAGAAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGAG

CGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGATGGCAAGTCAG

ATGTGAAAACTATGGGCTCAACCCATAGACTGCATTTGAAACTGTTGTTCTTGAGTGA

GGTAGAGGTAAGCGGAATTCCTGGTGTAGCGGTGAAATGCGTAGAGATCAGGAGGAA

CATCGGTGGCGAAGGCGGCTTACTGGGCCTTTACTGACGCTGAGGCTCGAAAGCGTG

GGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTACTAGG

TGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCTGGG

GAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGT

GGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCGA

GTGACGTACCTAGAGATAGGTATTTTCTTCGGAACACAAAGACAGGTGGTGCATGGTT

GTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTAC

CATTAGTTGCTACGCAAGAGCACTCTAATGGGACTGCCGTTGACAAAACGGAGGAAG

GTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTACTACAA

TGGCAATATAACAGAGGGAAGCAATACAGCGATGTGGAGCAAATCCCCAAAAATTGT

CCCAGTTCAGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATTGCTAGTAATCG

CAGATCAGCATGCTGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACAC

CATGGGAGTCGGTAACACCCAAAGCCGGTCGTCTAACCTTCGGGAGGATGCCGTCTA

AGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCG

GCTGGATCACCTCCTT (SEQ ID NO: 14)

GCF_000518765

Ruminococcus

ATAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCTTAACACATGCAA

flavefaciens

GTCGAACGGAGATAATTTGAGTTTACTTAGGTTATCTTAGTGGCGGACGGGTGAGTAA

CACGTGAGCAACCTACCTTAGAGAGAGGGATAGCTTCTGGAAACGGATGGTAATACC

TCATAACATAACTGAACCGCATGATTTAGTTATCAAAGATTTATCACTCTGAGATGGG

CTCGCGTCTGATTAGATAGTTGGTGAGGTAACGGCTCACCAAGTCGACGATCAGTAG

CCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACG

GGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGATGCCG

CGTGGAGGAAGAAGGTTTTCGGATTGTAAACTCCTGTCTTAAAGGACGATAATGACG

GTACTTTAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGG

GAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGAGCGCAAGT

CAGATGTGAAATACATGGGCTCAACCCATGGGCTGCATTTGAAACTGTGTTTCTTGAG

TGAAGTAGAGGTAAGCGGAATTCCTGGTGTAGCGGTGAAATGCGTAGATATCAGGAG

GAACACCGGTGGCGAAGGCGGCTTACTGGGCTTTTACTGACGCTGAGGCTCGAAAGC

GTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGATTACT

AGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCT

GGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGC

AGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACAT

CGTATGCATAGTCTAGAGATAGATGAAATTCCTTCGGGGACATATAGACAGGTGGTG

CATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAA

CCCTTACCTTTAGTTGCTACGCAAGAGCACTCTAAAGGGACTGCCGTTGACAAAACGG

AGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGT

ACTACAATGGCAATTAACAAAGAGAAGCAAGACGGTGACGTGGAGCGAATCTCAAA

AAATTGTCCCAGTTCAGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATTGCTA

GTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCC

GTCACACCATGGGAGTCGGTAACACCCGAAGTCGGTAGTCTAACAGCAATGAGGACG

CCGCCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGA

AGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 15)

GCF_000577335

Clostridium

CAAAGGAGCAATCCGCTGAAAGATGGACTCGCGTCCGATTAGCCAGTTGGCGGGGTA

jeddahense

AAGGCCCACCAAAGCGACGATCGGTAGCCGGGTTGAGAGACTGAACGGCCACATTGG

GACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATG

GAGGAAACTCTGATGCAGCAATGCCGCGTGAGGGAAGACGGTCTTCGGATTGTAAAC

CTCTGTCCTTGGTGAAGATAATGACGGTAGCCAAGGAGGAAGCTCCGGCTAACTACG

TGCCAGCAGCCGCGGTAATACGTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTA

AAGGGTGCGTAGGCGGCTTTTTAAGTCGGGCGTGAAAGCTGTGGGCTTAACCCACAA

ATTGCGTTCGAAACTGGAAGGCTTGAGTGAAGTAGAGGTAGGCGGAATTCCCGGTGT

AGCGGTGAAATGCGTAGAGATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGG

GCTTTAACTGACGCTGAGGCACGAAAGCATGGGTAGCAAACAGGATTAGATACCCTG

GTAGTCCATGCCGTAAACGATGATTACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCC

GGAGTTAACACAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAA

AGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACG

CGAAGAACCTTACCAGGTCTTGACATCCAACTAACGAGGCAGAGATGCATTAGGTGC

CCTTCGGGGAAAGTTGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGAT

GTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTGATTAGTTGCTACGCAAGAGCA

CTCTAATCAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATC

ATGCCCCTTATGACCTGGGCTACACACGTACTACAATGGTCGCTAACAGAGGGAAGC

CAAGCCGCGAGGTGGAGCAAACCCCCAAAAGCGATCTCAGTTCGGATTGTAGGCTGC

AACCCGCCTACATGAAGTTGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGA

ATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGGGAGCCGGTAATACCCG

AAGCCAATAGTCTAACCGCAAGGGGGACGTTGTCGAAGGTAGGATTGGCGACTGGGG

TGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ

ID NO: 16)

GCF_000620945

Clostridium viride
GCTTAGTGGCGGACGGGTGAGTAACGCGTGAGTAACCTGCCTTGGAGTGGGGAATAA

CACATCGAAAGGTGTGCTAATACCGCATGATGCAACGGGATCGCATGGTTCTGTTGCC

AAAGATTTATCGCTCTGAGATGGACTCGCGTCTGATTAGCTAGTTGGTGAGGTAATGG

CTCACCAAGGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACT

GAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGC

GCAAGCCTGACCCAGCAACGCCGCGTGAAGGAAGAAGGCCCTCGGGTTGTAAACTTC

TTTTATTCGAGACGAAACAAATGACGGTACCGAATGAATAAGCCACGGCTAACTACG

TGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTA

AAGGGCGTGTAGGCGGGACTGCAAGTCAGATGTGAAATTCCAGGGCTCAACTCTGGA

CCTGCATTTGAAACTGTAGTTCTTGAGTGATGGAGAGGCAGGCGGAATTCCGAGTGTA

GCGGTGAAATGCGTAGATATTCGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGAC

ATTAACTGACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGT

AGTCCACGCTGTAAACGATGGATACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCG

CAGTTAACACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAA

GGAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGC

GAAGAACCTTACCAGGGCTTGACATCCCTCTGACCGGTCTAGAGATAGGCCCTCCCTT

CGGGGCAGAGGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTG

GGTTAAGTCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACTCTA

GCGAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCC

CCTTATGTCCTGGGCTACACACGTACTACAATGGCGCTTAACAGAGGGAGGCAATAC

CGCGAGGTGGAGCAAACCCCTAAAAGGCGTCCCAGTTCGGATTGCAGGCTGAAACCC

GCCTGTATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACG

TTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGT

CCGTAGCCTAACAGCAATGAGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAA

GTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID

NO: 17)

GCF_000621285

Ruminococcus albus
TATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCTTAACACATGCA

AGTCGAACGAGCGAAAGAGTGCTTGCACTCTCTAGCTAGTGGCGGACGGGTGAGTAA

CACGTGAGCAATCTGCCTTTCGGAGAGGGATACCAATTGGAAACGATTGTTAATACCT

CATAACATAACGAAGCCGCATGACTTTGTTATCAAATGAATTTCGCCGAAAGATGAG

CTCGCGTCTGATTAGGTAGTTGGTGAGGTAACGGCCCACCAAGCCGACGATCAGTAG

CCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACG

GGAGGCAGCAGTGGGGAATATTGCACAATGGGCGAAAGCCTGATGCAGCGATGCCG

CGTGAGGGAAGAAGGTTTTAGGATTGTAAACCTCTGTCTTTGGGGACGATAATGACG

GTACCCAAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGG

GAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGATTGCAAGT

CAGGTGTGAAATTTAGGGGCTTAACCCCTGAACTGCACTTGAAACTGTAGTTCTTGAG

TGAAGTAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAG

GAACATCAGTGGCGAAGGCGGCTTACTGGGCTTTAACTGACGCTGAGGCTCGAAAGC

GTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTACT

AGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCT

GGGGAGTACGGCCGCAAGGCTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGC

AGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACAT

CGTACGCATAGCATAGAGATATGTGAAATCCCTTCGGGGACGTATAGACAGGTGGTG

CATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAA

CCCTTACTGTTAGTTGCTACGCAAGAGCACTCTAGCAGGACTGCCGTTGACAAAACGG

AGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGT

ACTACAATGGCTGTTAACAGAGGGAAGCAAAACAGTGATGTGGAGCAAAACCCTAA

AAGCAGTCTTAGTTCGGATTGTAGGCTGCAACCCGCCTACATGAAGTCGGAATTGCTA

GTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCC

GTCACGCCATGGGAGTCGGTAACACCCGAAGCCTGTGTTCTAACCGCAAGGAGGAAG

CAGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGA

AGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 18)

GCF_000701665

Agathobaculum

CAAGTTGGGAGTGAAATCCGGGGGCTTAACCCCCGAACTGCTTTCAAAACTGCTGGT

desmolans

CTTGAGTGATGGAGAGGCAGGCGGAATTCCGTGTGTAGCGGTGAAATGCGTAGATAT

ACGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGACATTAACTGACGCTGAGGCGC

GAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATG

GATACTAGGTGTGGGAGGTATTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTATC

CCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCA

CAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTT

GACATCCCGGTGACCGTCCTAGAGATAGGACTTCCCTTCGGGGCAACGGTGACAGGT

GGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGC

GCAACCCTTACGGTTAGTTGATACGCAAGATCACTCTAGCCGGACTGCCGTTGACAAA

ACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACAC

ACGTACTACAATGGCAGTCATACAGAGGGAAGCAAAATCGCGAGGTGGAGCAAATC

CCTAAAAGCTGTCCCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATGAAGTCGGAA

TTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACA

CCGCCCGTCACACCATGAGAGCCGTCAATACCCGAAGTCCGTAGCCTAACCGCAAGG

GGGGCGCGGCCGAAGGTAGGGGTGGTAATTAGGGTGAAGTCGTAACAAGGTAGCCG

TATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 19)

GCF_000723465

Ruminococcus

ATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCTTAACACATGCAA

bicirculans

GTCGAACGAGAGAAGAGGAGCTTGCTTTTCTGATCTAGTGGCGGACGGGTGAGTAAC

ACGTGAGCAATCTGCCTTTCAGAGGGGGATACCGATTGGAAACGATCGTTAATACCG

CATAACATAATTGAACCGCATGATTTGATTATCAAAGATTTATCGCTGAAAGATGAGC

TCGCGTCTGATTAGCTAGTTGGTAAGGTAACGGCTTACCAAGGCGACGATCAGTAGC

CGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGG

GAGGCAGCAGTGGGGAATATTGCACAATGGAGGAAACTCTGATGCAGCGATGCCGCG

TGAGGGAAGAAGGTTTTAGGATTGTAAACCTCTGTCTTCAGGGACGAAAAAAGACGG

TACCTGAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGG

AGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGATCGCAAGTC

AGATGTGAAAACTATGGGCTTAACCCATAAACTGCATTTGAAACTGTGGTTCTTGAGT

GAAGTAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGG

AACATCAGTGGCGAAGGCGGCTTACTGGGCTTTAACTGACGCTGAGGCTCGAAAGCG

TGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTACTA

GGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGCAAACGCAATAAGTAATCCACCTG

GGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCA

GTGGAGTATGTGGATTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATC

GTATGCATAGCTCAGAGATGAGTGAAATCTCTTCGGAGACATATAGACAGGTGGTGC

ATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAAC

CCTTACTGTTAGTTGCTACGCAAGAGCACTCTAGCAGGACTGCCGTTGACAAAACGG

AGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCCTCACACGT

ACTACAATGGCTGTCAACAGAGGGAAGCAAAGCCGCGAGGTGGAGCGAACCCCTAA

AAGCAGTCTTAGTTCGGATTGTAGGCTGCAACCCGCCTACATGAAGTCGGAATTGCTA

GTAATCGCAGATCAGCATGCTGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCC

GTCACGCCATGGGAGTCGGTAACACCCGAAGCCTGTAGTCTAACCGCAAGGAGGACG

CAGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGA

AGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 20)

GCF_000949455

Ruthenibacterium

AATGAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCA

lactatiformans

AGTCGAACGGAGCTGTTTTCTCTGAAGTTTTCGGATGGAAGAGAGTTCAGCTTAGTGG

CGAACGGGTGAGTAACACGTGAGCAACCTGCCTTTCAGTGGGGGACAACATTTGGAA

ACGAATGCTAATACCGCATAAGACCACAGTGTCGCATGGCACAGGGGTCAAAGGATT

TATCCGCTGAAAGATGGGCTCGCGTCCGATTAGCTAGATGGTGAGGTAACGGCCCAC

CATGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGAC

ACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAAC

CCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCTGTCC

CAGGGGACGATAATGACGGTACCCTGGGAGGAAGCACCGGCTAACTACGTGCCAGCA

GCCGCGGTAAAACGTAGGGTGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGC

GCAGGCGGATTGGCAAGTTGGGAGTGAAATCTATGGGCTCAACCCATAAATTGCTTT

CAAAACTGTCAGTCTTGAGTGGTGTAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGG

AATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACTAACT

GACGCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCAT

GCCGTAAACGATGATTACTAGGTGTGGGAGGATTGACCCCTTCCGTGCCGCAGTTAAC

ACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGA

CGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACC

TTACCAGGTCTTGACATCGGATGCATACCTAAGAGATTAGGGAAGTCCTTCGGGACAT

CCAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCC

CGCAACGAGCGCAACCCTTATCGTTAGTTACTACGCAAGAGGACTCTAGCGAGACTG

CCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGAC

CTGGGCTACACACGTACTACAATGGCTATTAACAGAGAGAAGCGATACCGCGAGGTG

GAGCAAACCTCACAAAAATAGTCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGT

GAAGCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGG

CCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTC

TAACCGTAAGGAGGACGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAAC

AAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 21)

GCF_001244495

Clostridium

TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

phoceensis

GTCGAACGGAGTGCCTTAGAAAGAGGATTCGTCCAATTGATAAGGTTACTTAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTCGGAGTGGGGAATAACAGACCGAA

AGGCCTGCTAATACCGCATGATGCAGTTGGACCGCATGGTCCTGACTGCCAAAGATTT

ATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTTGTTGGCGGGGTAATGGCCCACCAA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTCTCAGG

GACGAACAAATGACGGTACCTGAGGAATAAGCCACGGCTAACTACGTGCCAGCAGCC

GCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTGTA

GGCGGGAAGGCAAGTCAGATGTGAAAACTATGGGCTCAACCCATAGCCTGCATTTGA

AACTGTTTTTCTTGAGTGCTGGAGAGGCAATCGGAATTCCGTGTGTAGCGGTGAAATG

CGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACAGTAACTGACG

CTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTG

TAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGCAGTTAACACA

ATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGACGG

GGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTA

CCAGGGCTTGACATCCTACTAACGAAGCAGAGATGCATTAGGTGCCCTTCGGGGAAA

GTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGT

CCCGCAACGAGCGCAACCCTTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAGACT

GCCGTTGACAAAACGGAGGAAGGCGGGGACGACGTCAAATCATCATGCCCCTTATGT

CCTGGGCTACACACGTACTACAATGGTGGTAAACAGAGGGAAGCAAGACCGCGAGGT

GGAGCAAATCCCTAAAAGCCATCCCAGTTCGGATTGCAGGCTGAAACCCGCCTGTAT

GAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGG

CCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTAGTC

TAACCGCAAGGGGGACGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCGTAAC

AAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 22)

GCF_001244995

Intestinimonas

TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

massiliensis

GTCGAACGGAACGCCAAGGAAAGAGTTTTCGGACAATGGAATTGGTTGTTTAGTGGC

GGACGGGTGAGTAACGCGTGAGTAACCTGCCTTGGAGTGGGGAATAACACAGTGAAA

ATTGTGCTAATACCGCATGATATATTGGTGTCGCATGGCACTGATATCAAAGATTTAT

CGCTCTGAGATGGACTCGCGTCTGATTAGATAGTTGGCGGGGTAACGGCCCACCAAG

TCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTGA

CCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTAACAGG

GACGAAGCAAGTGACGGTACCTGTTGAATAAGCCACGGCTAACTACGTGCCAGCAGC

CGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTGT

AGGCGGGACTGCAAGTCAGATGTGAAAACTATGGGCTCAACCCATAGCCTGCATTTG

AAACTGTAGTTCTTGAGTGTCGGAGAGGCAATCGGAATTCCGTGTGTAGCGGTGAAA

TGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACGATAACTGA

CGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGC

CGTAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGCAGCTAACG

CAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGAC

GGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCT

TACCAGGGCTTGACATCCTACTAACGAACCAGAGATGGATTAGGTGCCCTTCGGGGA

AAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAA

GTCCCGCAACGAGCGCAACCCTTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAG

ACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTA

TGTCCTGGGCCACACACGTACTACAATGGCGGTTAACAGAGGGAGGCAAAGCCGCGA

GGCAGAGCAAACCCCTAAAAGCCGTCCCAGTTCGGATTGCAGGCTGAAACCCGCCTG

TATGAAGTCGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCC

GGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTA

GCCTAACTGCAAAGGGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCGT

AACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 23)

GCF_001261775

Anaeromassilibacillus

TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

senegalensis

AGTCGAACGGAGTTAGAAGAGCTTGCTCTTCTAACTTAGTGGCGGACGGGTGAGTAA

CGCGTGAGTAACCTGCCTTTCAGAGGGGGATAACGTTCTGAAAAGAACGCTAATACC

GCATGACGTCATAGTACCGCATGGTACAGTGATCAAAGGAGCAATCCGCTGAAAGAT

GGACTCGCGTCCGATTAGCTAGTTGGTGGGGTAAAGGCTCACCAAGGCGACGATCGG

TAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCT

ACGGGAGGCAGCAGTGGGGGATATTGCACAATGGGGGAAACCCTGATGCAGCAACG

CCGCGTGAAGGAAGAAGGTCTTCGGATTGTAAACTTCTGTCCTATGGGAAGATAATG

ACGGTACCATAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGT

AGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGATCTGCA

AGTCAGTAGTGAAATCCCGGGGCTTAACCCCGGAACTGCTATTGAAACTGTGGGTCTT

GAGTGAGGTAGAGGCAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGAGATCG

GGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCCTTAACTGACGCTGAGGCACGA

AAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGAT

TACTAGGTGTGGGTGGTCTGACCCCATCCGTGCCGGAGTTAACACAATAAGTAATCCA

CCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACA

AGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGA

CATCCTACTAACGAAGCAGAGATGCATTAGGTGCCTTTCGGGGAAAGTAGAGACAGG

TGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAG

CGCAACCCTTGCTATTAGTTGCTACGCAAGAGCACTCTAATAGGACTGCCGTTGACAA

AACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACA

CACGTACTACAATGGTCGTTAACAGAGAGAAGCAATACTGCGAAGTGGAGCAAAACT

CTAAAAACGGTCTCAGTTCGGATTGTAGGCTGCAACCCGCCTACATGAAGTTGGAATT

GCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACC

GCCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCAGTAGTCTAACCGCAAGGAG

GACGCTGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCGTAT

CGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 24)

GCF_001312825

Ruminococcus

TATGAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCCTAACACATGCA

champanellensis

AGTCGAACGGAGATAAAGACTTCGGTTTTTATCTTAGTGGCGGACGGGTGAGTAACA

CGTGAGCAACCTGCCTCTGAGAGAGGGATAGCTTCTGGAAACGGATGGTAATACCTC

ATAACATAGCGGTACCGCATGATACTGCTATCAAAGATTTATCGCTCAGAGATGGGCT

CGCGTCTGATTAGCTAGATGGTGAGGTAACGGCTCACCATGGCGACGATCAGTAGCC

GGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGG

AGGCAGCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAGCGATGCCGCGT

GGAGGAAGAAGGTTTTCGGATTGTAAACTCCTGTCTTAAGGGACGATAATGACGGTA

CCTTAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGAG

CGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGATTGCAAGTCAG

ATGTGAAAACTATGGGCTTAACCCATAGACTGCATTTGAAACTGTAGTTCTTGAGTGA

AGTAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAA

CATCGGTGGCGAAGGCGGCTTACTGGGCTTTTACTGACGCTGAGGCTCGAAAGCGTG

GGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGATTACTAGG

TGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCTGGG

GAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGT

GGAGTATGTGGTTTAATTCGAAGCAACGCGAAAAACCTTACCAGGTCTTGACATCGA

GTGAATGATCTAGAGATAGATCAGTCCTTCGGGACACAAAGACAGGTGGTGCATGGT

TGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTA

CCTTTAGTTGCTACGCAAGAGCACTCTAGAGGGACTGCCGTTGACAAAACGGAGGAA

GGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTACTACA

ATGGCAATGAACAGAGGGAAGCAATACAGTGATGTGGAGCAAATCCCCAAAAATTGT

CCCAGTTCAGATTGTAGGCTGCAACTCGCCTACATGAAGTCGGAATTGCTAGTAATCG

CAGATCAGCATGCTGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACAC

CATGGAGTCGGTAACACCCGAAGCCAGTAGCCTAACCGCAAGGAGGGCGCTGTCGAA

GGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGG

CTGGATCACCTCCTTT (SEQ ID NO: 25)

GCF_001486165

Bittarella

ATAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

massiliensis

GTCGAACGGACACATCCGACGGAATAGCTTGCTAGGAAGATGGATGTTGTTAGTGGC

GGACGGGTGAGTAACACGTGAGCAACCTGCCTCGGAGTGGGGGACAACAGTTGGAA

ACGACTGCTAATACCGCATACGGTGGTCGGGGGACATCCCCTGGCTAAGAAAGGATC

TATGATCCGCTCTGAGATGGGCTCGCGTCTGATTAGCTAGTTGGCGGGGTAACGGCCC

ACCAAGGCAACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAG

ACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGGA

ACCCTGATGCAGCGACGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAAACCTCTGT

CTTGTGGGACGATAATGACGGTACCACAGGAGGAAGCCATGGCTAACTACGTGCCAG

CAGCCGCGGTAATACGTAGATGGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGA

GTGTAGGCGGGATCATAAGTTGCGTGTGAAATGCAGGGGCTCAACCCCTGAACTGCG

CGCAAAACTGTGGTTCTTGAGTGAAGTAGAGGCAGGCGGAATTCCCGGTGTAGCGGT

GGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTTA

CTGACGCTGAGGCTCGAAAGCATGGGGAGCAAACAGGATTAGATACCCTGGTAGTCC

ATGCCGTAAACGATGATTACTAGGTGTGGGGGGATAACCCCCTCCGTGCCGGAGTTA

ACACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATT

GACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAAAA

CCTTACCAGGTCTTGACATCTATCGCTATCCCAAGAGATTGGGAGTTCCCTTCGGGGA

CGGTAAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAG

TCCCGCAACGAGCGCAACCCTTACTGTTAGTTGCTACGCAAGAGCACTCTAACGGGA

CTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTAT

GACCTGGGCTACACACGTACTACAATGGCCGCAAACAACGAGCAGCGAAACCGCGA

GGTGGAGCGAATCTATAAAAGCGGTCTCAGTTCGGATTGCAGGCTGCAACTCGCCTG

CATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCC

GGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGTAACACCCGAAGTCAGTA

GTCTAACCGCAAGGGGGACGCTGCCGAAGGTGGGGCTGGTGATTGGGGTGAAGTCGT

AACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 26)

GCF_002157465

Butyricicoccus

TTTAGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCA

porcorum

AGTCGAACGGAGCACTGAGACTTCGGTTTTTGTGCTTAGTGGCGGACGGGTGAGTAA

CGCGTGAGCAATCTGCCTTTCAGAGGGGGATAACGACTGGAAACGGTCGCTAATACC

GCATAACGTATTTTGCAGGCATCTGCGAGATACCAAAGGAGCAATCCGCTGAAAGAT

GAGCTCGCGTCTGATTAGATAGTTGGTGAGGTAACGGCCCACCAAGTCGACGATCAG

TAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCT

ACGGGAGGCAGCAGTGGGGAATATTGCGCAATGGGGGAAACCCTGACGCAGCAACG

CCGCGTGATCGAAGAAGGTCTTCGGATTGTAAAGATCTTTTATCAGGGACGAAGAAA

GTGACGGTACCTGATGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATA

CGTAGGGAGCGAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGAGTAGGCGGGCTG

GTAAGTTGGAAGTGAAATGTCGGGGCTTAACCCCGGAACTGCTTTCAAAACTGCTGG

TCTTGAGTGATGGAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATA

TTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGACATTAACTGACGCTGAGGAG

CGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGAT

GGATACTAGGTGTGGGAGGTATTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAT

CCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGC

ACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCTGGTCT

TGACATCCCGGTGACCGGCATAGAGATATGCCTTTCCCTTCGGGGACAGCGGTGACA

GGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACG

AGCGCAACCCTTATTGTTAGTTGATACATTTAGTTGATCACTCTAGCGAGACTGCCGT

TGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCAGG

GCTACACACGTACTACAATGGCAGACATACAGAGGGAAGCAAAGCTGTGAGGCAGA

GCAAATCCCTAAAAGCTGTCCCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATGAA

GTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTT

GTACACACCGCCCGTCACACCATGAGAGCCGGTAATGCCCGAAGTCCGTAGTCTAAC

CGCAAGGAGGACGCGGCCGAAGGCAGGACTGGTAATTAGGGTGAAGTCGTAACAAG

GTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 27)

GCF_002201475

Acutalibacter muris
TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAATACATGCA

AGTCGAACGGAGATATTCGCTGATGAAGTACTTCGGTAATGAATCTTGGATATCTTAG

TGGCGGACGGGTGAGTAACGCGTGAGCAACCTGCCTTTCAGAGGGGGATAACGTTTG

GAAACGAACGCTAATACCGCATGACATTATCTTATCGCATGGTAGGATAATCAAAGG

AGCAATCCGCTGAAAGATGGGCTCGCGTCCGATTAGGTAGTTGGTGGGGTAACGGCC

CACCAAGCCGACGATCGGTAGCCGGACTGAGAGGTTGGACGGCCACATTGGGACTGA

GACACGGCCCAGACTCCTACGGGAGGCAGCAGTAAGGGATATTGGTCAATGGGGGA

AACCCTGAACCAGCAACGCCGCGTGAGGGAAGACGGTTTTCGGATTGTAAACCTCTG

TCCTCTGTGAAGATGATGACGGTAGCAGAGGAGGAAGCTCCGGCTAACTACGTGCCA

GCAGCCGCGGTAATACGTAGGGAGCGAGCGTTGTCCGGATTTACTGGGTGTAAAGGG

TGCGTAGGCGGCTTGGCAAGTCAGTAGTGAAATCCATGGGCTTAACCCATGAACTGC

TATTGAAACTGTCGAGCTTGAGTGAAGTAGAGGTAGGCGGAATTCCCGGTGTAGCGG

TGAAATGCGTAGAGATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCTTTA

ACTGACGCTGAGGCACGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTC

CACGCTGTAAACGATGATTACTAGGTGTGGGTGGACTGACCCCATCCGTGCCGGAGTT

AACACAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGCTGAAACTCAAAGGAAT

TGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGATTAATTCGATGCAACGCGAAGA

ACCTTACCAGGTCTTGACATCCCGCTAACGAGGTAGAGATACGTTAGGTGCCCTTCGG

GGAAAGCGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGG

TTAAGTCCCGCAACGAGCGCAACCCTTACTGTTAGTTGCTACGCAAGAGCACTCTAGC

AGGACCGCCGTTGACAAAACGGAGGAAGGTGGGGATGATGTCAAATCATCATGCCCC

TTATGACCTGGGCCTCACACGTACTACAATGGCCATTAACAGAGGGAGGCAAAGCCG

CGAGGCAGAGCAAAACCCTAAAAATGGTCCCAGTTCGGATCGCAGGCTGCAACCCGC

CTGCGTGAAGTTGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTC

CCGGGCCTTGTACACACCGCCCGTCACACCATGGAAGTCGGTAATGCCCGAAGTCAG

TAGCCTAACCGCAAGGGGGGCGCTGCCGAAGGCAGGATTGATGACTGGGGTGAAGTC

GTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 28)

GCF_002556665

Clostridium leptum
TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

AGTCGAACGGAGTTAAATTCGACACCCGAGTATCCGGCCGGGAGGCGGGGTGCTGGG

GGTTGGATTTAACTTAGTGGCGGACGGGTGAGTAACGCGTGAGTAACCTGCCTTTCAG

AGGGGGATAACGTTCTGAAAAGAACGCTAATACCGCATAACATCAATTTATCGCATG

ATAGGTTGATCAAAGGAGCAATCCGCTGGAAGATGGACTCGCGTCCGATTAGCCAGT

TGGCGGGGTAACGGCCCACCAAAGCGACGATCGGTAGCCGGACTGAGAGGTTGAAC

GGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGAT

ATTGCACAATGGGGGAAACCCTGATGCAGCAACGCCGCGTGAGGGAAGAAGGTTTTC

GGATTGTAAACCTCTGTTCTTAGTGACGATAATGACGGTAGCTAAGGAGAAAGCTCC

GGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGAGCGAGCGTTGTCCGGATT

TACTGGGTGTAAAGGGTGCGTAGGCGGCGAGGCAAGTCAGGCGTGAAATCTATGGGC

TTAACCCATAAACTGCGCTTGAAACTGTCTTGCTTGAGTGAAGTAGAGGTAGGCGGA

ATTCCCGGTGTAGCGGTGAAATGCGTAGAGATCGGGAGGAACACCAGTGGCGAAGGC

GGCCTACTGGGCTTTAACTGACGCTGAAGCACGAAAGCATGGGTAGCAAACAGGATT

AGATACCCTGGTAGTCCATGCCGTAAACGATGATTACTAGGTGTGGGGGGTCTGACC

CCCTCCGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGG

TTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAAT

TCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCGTCTAACGAAGCAGAGAT

GCATTAGGTGCCCTTCGGGGAAAGGCGAGACAGGTGGTGCATGGTTGTCGTCAGCTC

GTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTTTCTAGTTGCT

ACGCAAGAGCACTCTAGAGAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGA

CGTCAAATCATCATGCCCCTTATGACCTGGGCCACACACGTACTACAATGGCTGTAAA

CAGAGGGAAGCAAAGCCGCGAGGTGGAGCAAAACCCTAAAAGCAGTCCCAGTTCGG

ATCGCAGGCTGCAACCCGCCTGCGTGAAGTCGGAATTGCTAGTAATCGCGGATCAGC

ATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGGGAG

CCGGTAATACCCGAAGCCAGTAGTTCAACCGCAAGGAGAGCGCTGTCGAAGGTAGGA

TTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATC

ACCTCCTTT (SEQ ID NO: 29)

GCF_002834225

Ruminococcus

TTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAA

bromii

GTCGAACGGAACTGTTTTGAAAGATTTCTTCGGAATGAATTTGATTTAGTTTAGTGGC

GGACGGGTGAGTAACGCGTGAGTAACCTGCCTTCAAGAGGGGGATAACATTCTGAAA

AGAATGCTAATACCGCATGACATATCGGAACCACATGGTTCTGATATCAAAGATTTTA

TCGCTTGAAGATGGACTCGCGTCCGATTAGTTAGTTGGTGAGGTAACGGCTCACCAAG

ACCGCGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCGCAATGGGGGCAACCCTGA

CGCAGCAACGCCGCGTGAAGGATGAAGGTTTTCGGATTGTAAACTTCTTTTATTAAGG

ACGAAAAATGACGGTACTTAATGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGC

GGTAATACGTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGG

CGGCTTTGCAAGTCAGATGTGAAATCTATGGGCTCAACCCATAAACTGCATTTGAAAC

TGTAGAGCTTGAGTGAAGTAGAGGCAGGCGGAATTCCCCGTGTAGCGGTGAAATGCG

TAGAGATGGGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACGCT

GAGGCACGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTA

AACGATGATTACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAAT

AAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGG

GCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACC

AGGTCTTGACATCCAACTAACGAAGTAGAGATACATTAGGTGCCCTTCGGGGAAAGT

TGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCC

CGCAACGAGCGCAACCCTTGCTATTAGTTGCTACGCAAGAGCACTCTAATAGGACTG

CCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGAC

CTGGGCTACACACGTACTACAATGGATGTTAACAGAGGGAAGCAAGACAGTGATGTG

GAGCAAACCCCTAAAAACATTCTCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATG

AAGATGGAATTGCTAGTAATCGCGGATCAGAATGCCGCGGTGAATACGTTCCCGGGC

CTTGTACACACCGCCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCAGTAGTCC

AACCTCGTGAGGACGCTGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAA

GGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 30)

GCF_002874775

Monoglobus

ATCGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAA

pectinilyticus

GTCGAGCGAGAAATTTTTAACGGATCCCTTCGGGGAGAAGATAAGGATGGAAAGCGG

CGGACGGGTGAGTAACGCGTGAGTAACCTGCCTTTAGGAGGGGGACAACATTCCGAA

AGGGATGCTAATACCGCATAAAATTATTGTATCGCATGGTATAATAATCAAAGATTTA

TCGCCTAAAGATGGACTCGCGTCCGATTAGCTAGTTGGTGGGGTAAAAGCCTACCAA

GGCGACGATCGGTAGCCGAACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCGCAATGGGGGAAACCCTG

ACGCAGCAACGCCGCGTGAAGGAAGAAGGCCTTCGGGTTGTAAACTTCTTTAAGTGT

GGAAGATAATGACGGTACACACAGAATAAGCCACGGCTAACTACGTGCCAGCAGCCG

CGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGTGTAG

GCGGGTAGACAAGTCAGATGTGAAATACCGGGGCTCAACTCCGGGGCTGCATTTGAA

ACTGTATATCTTGAGTGTCGGAGAGGAAAGCGGAATTCCTAGTGTAGCGGTGAAATG

CGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTTCTGGACGATAACTGACG

CTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCG

TAAACGATGGATACTAGGTGTAGGAGGTATCGACCCCTTCTGTGCCGCAGTTAACAC

AATAAGTATCCCACCTGGGGAGTACGGTCGCAAGATTGAAACTCAAAGGAATTGACG

GGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTT

ACCAGGACTTGACATCCCACGCATAGCCTAGAGATAGGTGAAGTCCTACGGGACGTG

GAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCC

GCAACGAGCGCAACCCTTACTGTCAGTTACCATCATTAAGTTGGGGACTCTGGCAGG

ACTGCCGGTGACAAATCGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTA

TGTCCTGGGCTACACACGTACTACAATGGCTGTTAACAAAGTGAAGCAAAGCAGTGA

TGTGGAGCAAAACACAAAAAGCAGTCTCAGTTCAGATTGTAGGCTGAAACTCGCCTA

TATGAAGTCGGAATTGCTAGTAATCGCAGATCAGCATGCTGCGGTGAATACGTTCCCG

GGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGATAACACCCGAAGCCTGTAG

CTTAACCTTAGGGAGAGCGCAGTCGAAGGTGGGATTGATAATTAGGGTGAAGTCGTA

ACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 31)

GCF_003020045

Ethanoligenens

TTGGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

harbinense

GTCGAGCGGAGTCCTTCGGGACTTAGCGGCGGACGGGTGAGTAACGCGTGAGCAACC

TGGCCTTCAGAGGGGGATAACGTCTGGAAACGGACGCTAATACCGCATGACATGGCG

GAGTCGCATGGCTCTGCCATCAAAGGAGTAATCCGCTGAGGGATGGGCTCGCGTCCG

ATTAGGTAGTTGGTGAGGTAACGGCTCACCAAGCCCGCGATCGGTAGCCGGACTGAG

AGGTTGGCCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCA

GTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCGACGCCGCGTGAGGGAA

GAAGGTCTTCGGATTGTAAACCTCTGTCTTTGGGGACGAATCAATGACGGTACCCAAG

GAGGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCG

TTGTCCGGAATTACTGGGTGTAAAGGGTGCGCAGGCGGGGCGGCAAGTTGGATGTGA

AAACTCCGGGCTCAACCCGGAGCCTGCATTCAAAACTGTCGCTCTTGAGTGAAGTAG

AGGCAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGATATCGGGAGGAACACCA

GTGGCGAAGGCGGCCTGCTGGGCTTTTACTGACGCTGAGGCACGAAAGCATGGGTAG

CAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGATTGCTAGGTGTGG

GGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAATAAGCAATCCACCTGGGGAGTA

CGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGT

ATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCACCGAAT

CCCCCAGAGATGGGGGAGTGCCCTTCGGGGAGCGGTGAGACAGGTGGTGCATGGTTG

TCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTG

AATAGTTGCTACGAAAGAGCACTCTATTCAGACCGCCGTTGACAAAACGGAGGAAGG

TGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTACTACAAT

GGCCATCAACAGAGGGAAGCAAGGCCGCGAGGTGGAGCGAACCCCTAAAAATGGTC

TCAGTTCAGATTGCAGGCTGAAACCCGCCTGCATGAAGATGGAATTGCTAGTAATCG

CGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACAC

CATGAGAGCCGGGGACACCCGAAGTCGGTTGGGTAACCGTAAGGAGCCCGCCGCCGA

AGGTGGAATCGGTAATTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCG

GCTGGATCACCTCCTTT (SEQ ID NO: 32)

GCF_900048895

Neglecta timonensis
TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

AGTCGAACGGAGATAGACGCTGAAAGGGAGACAGCTTGCTGTAAGAATTTCTTGTTT

ATCTTAGTGGCGGACGGGTGAGTAACGCGTGAGTAACCTGCCTTTCAGAGGGGGATA

ACGTCTGGAAACGGACGCTAATACCGCATGAGACCACAGCTTCACATGGAGCGGCGG

TCAAAGGAGCAATCCGCTGAAAGATGGACTCGCGTCCGATTAGATAGTTGGCGGGGT

AACGGCCCACCAAGTCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTG

GGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGAGGGATATTGGTCAAT

GGGGGAAACCCTGAACCAGCAACGCCGCGTGAGGGAAGACGGTTTTCGGATTGTAAA

CCTCTGTCCTCTGTGAAGATAGTGACGGTAGCAGAGGAGGAAGCTCCGGCTAACTAC

GTGCCAGCAGCCGCGGTAATACGTAGGGAGCGAGCGTTGTCCGGATTTACTGGGTGT

AAAGGGTGCGTAGGCGGCTCTGCAAGTCAGAAGTGAAATCCATGGGCTTAACCCATG

AACTGCTTTTGAAACTGTAGAGCTTGAGTGAAGTAGAGGTAGGCGGAATTCCCGGTG

TAGCGGTGAAATGCGTAGAGATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTG

GGCTTTAACTGACGCTGAGGCACGAAAGCATGGGTAGCAAACAGGATTAGATACCCT

GGTAGTCCATGCCGTAAACGATGATTACTAGGTGTGGGGGGTCTGACCCCCTCCGTGC

CGGAGTTAACACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCA

AAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGATTAATTCGAAGCAAC

GCGAAGAACCTTACCAGGTCTTGACATCCAACTAACGAAGCAGAGATGCATTAGGTG

CCCTTCGGGGAAAGTTGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAG

ATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTACTGTTAGTTGCTACGCAAGAGC

ACTCTAGCAGGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCAT

CATGCCCCTTATGACCTGGGCCTCACACGTACTACAATGGCCATTAACAGAGGGAAG

CAAGCCCGCGAGGTGGAGCAAAACCCTAAAAATGGTCTCAGTTCGGATCGTAGGCTG

AAACCCGCCTGCGTGAAGTTGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTG

AATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGGGAGCCGGTAATACCC

GAAGTCAGTAGTCTAACCGCAAGGGGGACGCTGCCGAAGGTAGGATTGGCGACTGGG

GTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ

ID NO: 33)

GCF_900078395

Anaerotruncus

AAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAAGT

rubiinfantis

CGAACGGAGTTTATCCGACTGAAGTTTTCGGATGGAAGATGGATAAACTTAGTGGCG

GACGGGTGAGTAACACGTGAGCAACCTGCCTTTCAGAGGGGGATAACGATTGGAAAC

GATCGCTAATACCGCATAACATTATGAGGAGACATCTTCTTATAATCAAAGGAGCAA

TCCGCTGAAAGATGGGCTCGCGGCCGATTAGCTAGATGGTGGGGTAACGGCCCACCA

TGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGAGGAAACTCT

GATGCAGCGACGCCGCGTGAGGGAAGACGGTCTTCGGATTGTAAACCTCTGTCTTAG

GGGAAGAAAATGACGGTACCCTAAGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCC

GCGGTAATACGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTA

GGCGGGATGGCAAGTTGGATGTTTAAACTAACGGCTCAACTGTTAGGTGCATCCAAA

ACTGCTGTTCTTGAGTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATG

CGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACG

CTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTG

TAAACGATGATTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACA

ATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGG

GGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTA

CCAGGTCTTGACATCGGATGCATACCATAGAGATATGGGAAGTCCTTCGGGACATCC

AGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCG

CAACGAGCGCAACCCTTATTATTAGTTGCTACGCAAGAGCACTCTAATGAGACTGCCG

TTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTG

GGCTACACACGTACTACAATGGCACTTAAACAAAGGGCAGCAACGTCGCGAGGCGAA

GCGAATCCCGAAAAAGTGTCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAA

GTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTT

GTACACACCGCCCGTCACACCATGGGAGTCGGTAACACCCGAAGCCAGTAGTCTAAC

TGCAAAGAGGACGCTGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGG

TAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 34)

GCF_900095865

Massilioclostridium

ATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

coli

GTCGAACGGAGATACCTGTTAGATCCCTTCGGGGTGACGATGGACTATCTTAGTGGCG

GACGGGTGAGTAACACGTGAGCAACCTGCCTTACAGAGTGGGATAACGTTTGGAAAC

GAACGCTAATACCGCATAACATTAACTTATCGCATGGTAAGATAATCAAAGAAATTC

GCTGTAAGATGGGCTCGCGTCTGATTAGATAGTTGGTGAGGTAACGGCTCACCAAGT

CGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGC

CCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGAT

GCAGCGACGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAAACCTCTGTCTTCAGGG

ACGATAGTGACGGTACCTGAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCG

GTAATACGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGC

GGGACAGCAAGTTGAATGTGAAATCTATGGGCTCAACCCATAAACTGCGTTCAAAAC

TGTTGTTCTTGAGTGAAGTAGAGGTAGGCGGAATTCCTAGTGTAGCGGTGAAATGCGT

AGATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCTTTAACTGACGCTG

AGGCTCGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAA

ACGATGATTACTAGGTGTNNNNNNNTCAACCTTCCGTGCCGGAGTTAACACAATAAG

TAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCC

CGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGG

TCTTGACATCCAACTAACGAGATAGAGATATGTTAGGTGCCCTTCGGGGAAAGTTGA

GACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGC

AACGAGCGCAACCCTTACCATTAGTTGCTACGCAAGAGCACTCTAATGGGACTGCCG

TTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTG

GGCCACACACGTACTACAATGGCTATTAACAGAGGGAAGCAATACCGCGAGGAGGA

GCAAACCCCTAAAAATAGTCTCAGTTCGGATTGCAGGCTGCAACCCGCCTGCATGAA

GCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTT

GTACACACCGCCCGTCACACCATGAGAGTTGGCAACACCCGAAGCCAGTAGCCTAAC

CGCAAGGAGGGCGCTGTCGAAGGTGGGGTTGATGATTAGGGTGAAGTCGTAACAAGG

TAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 35)

GCF_900104675

Angelakisella

AATGAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCA

massiliensis

AGTCGAACGGAGTAAGATGAGCTTGCTTATCTTACTTAGTGGCGGACGGGTGAGTAA

CACGTGAGCAACCTGCCTTCGAGTGGGGAATAACAGTCGGAAACGACTGCTAATACC

GCATAACACATTGGGATGGCATCATCCTGATGTCAAAGATTTATCGCTCGAAGATGG

GCTCGCGTCCGATTAGCTAGTTGGCGGGGTAACGGCCCACCAAGGCGACGATCGGTA

GCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTAC

GGGAGGCAGCAGTGGGGGATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCC

GCGTGTAGGAAGACGGTCCTCTGGATTGTAAACTACTGTCTTCAGGGACGATAATGA

CGGTACCTGAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTA

GGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGGAGGCA

AGTTGGATGTGAAAACTATCGGCTCAACTGATAGACTGCATTCAAAACTGTTTCTCTT

GAGTGAAGTAGAGGCAGGCGGGATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAG

GAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTTACTGACGCTGAGGCTCGAA

AGTGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACACCGTAAACGATGATT

ACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAATCCA

CCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACA

AGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGA

CATCTCCTGCATAACCTAGAGATAGGTGAAGTCCTTCGGGACAGGAAGACAGGTGGT

GCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCA

ACCCTTGTTTTTAGTTGCTACGCAAGAGCACTCTAAAGAGACTGCCGTTGACAAAACG

GAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACG

TACTACAATGGCAATTAACAGAGGGAAGCGACACCGCGAGGTGGAGCAAAACCCTA

AAAATTGTCCCAGTTCAGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATTGCT

AGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGC

CCGTCACACCATGGGAGTCGGTAACACCCGAAGTCAGTAGCCTAACCGCAAGGAGGG

CGCTGCCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCG

GAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 36)

GCF_900130065

Sporobacter

TATTGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

termitidis

AGTCGAACGGAGACAATTGGTTCGCTGATTGTCTTAGTGGCGGACGGGTGAGTAACG

CGTGAGCAATCTGCCCTTCGGAGGGGGACAACAGCTGGAAACGGCTGCTAATACCGC

ATAATGTATATTCAAGGCATCTTGGATATACCAAAGATTTATCGCCGAAGGATGAGCT

CGCGTCTGATTAGCTAGTTGGTGAGGTAAAGGCTCACCAAGGCTGCGATCAGTAGCC

GGACTGAGAGGTTGAACGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGG

AGGCAGCAGTGGGGAATATTGGGCAATGGGGGCAACCCTGACCCAGCAACGCCGCGT

GAAGGAAGAAGGCCTTCGGGTTGTAAACTTCTTTGACCAGGGACGAAACAAATGACG

GTACCTGGAAAACAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGG

TGGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGCGTAGGCGGGAGTACAAGT

CAGATGTGAAATCTGGGGGCTTAACCCTCAAACTGCATTTGAAACTGTATTTCTTGAG

TATCGGAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAG

GAACACCAGTGGCGAAGGCGGCCTGCTGGACGACAACTGACGCTGAGGCGCGAAAG

CGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGAATAC

TAGGTGTGGGGGGACTGACCCCCTCCGTGCCGGAGTTAACACAATAAGTATTCCACCT

GGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGC

AGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGGCTTGACAT

CGTACTAACGAAGCAGAGATGCATTAGGTGCCCTTCGGGGAAAGTATAGACAGGTGG

TGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGC

AACCCCTATTGTTAGTTGCTACGCGAGAGCACTCTAGCGAGACTGCCGTTGACAAAAC

GGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGTCCTGGGCTACACAC

GTAATACAATGGCGCTCAACAGAGGGAAGCAAGACCGCGAGGTGGAGCAAATCCCT

AAAAGGCGTCTCAGTTCAGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATTG

CTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCG

CCCGTCACACCATGAGAGCCGGGAACACCCGAAGTCCGTAGTCTAACCGCAA (SEQ

ID NO: 37)

GCF_900148495

Negativibacillus

ACAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

massiliensis

GTCGAACGGAGTTGTGTTGAAAGCTTGCTGGATATACAACTTAGTGGCGGACGGGTG

AGTAACACGTGAGTAACCTGCCTCTCAGAGTGGAATAACGTTTGGAAACGAACGCTA

ATACCGCATAACGTGAGAAGAGGGCATCCTCTTTTTACCAAAGATTTATCGCTGAGAG

ATGGGCTCGCGGCCGATTAGGTAGTTGGTGAGATAACAGCCCACCAAGCCGACGATC

GGTAGCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAGACTC

CTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGGGGAAACCCTGATGCAGCGA

CGCCGCGTGAGGGAAGACGGTTTTCGGATTGTAAACCTCTGTCTTTAGGGACGAAAA

AATGACGGTACCTAAGGAGGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAAT

ACGTAGGTGGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGGA

GACAAGTTGAATGTCTAAACTATCGGCTTAACTGATAGTCGCGTTCAAAACTATCACT

CTTGAGTGCAGTAGAGGTAGGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATAT

TAGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCTGTAACTGACGCTGAGGCTC

GAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATG

ATTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAAT

CCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCA

CAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTT

GACATCGAGCGACGAACCAAGAGATTGGTTCTTCCTTCGGGACGCGAAGACAGGTGG

TGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGC

AACCCTTATCATTAGTTGCTACGCAAGAGCACTCTAATGAGACTGCCGTTGATAAAAC

GGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACAC

GTACTACAATGGTGATCAAACAGAGGGAAGCAACACAGCGATGTGAAGCAAATCCC

GAAAAATCATCTCAGTTCAGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATT

GCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACC

GCCCGTCACACCATGGGAGTCGGTAACACCCGAAGCCAGTAGCCTAACCGCAAGGAG

GGCGCTGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTAT

CGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 38)

GCF_900155615

Massilimaliae

AAAGAGTTTGATCCTGGCTCAGGACGAACGCTGTCGGCGCGCCTAACACATGCAAGT

massiliensis

CGAACGAAGCTGCATCGAACGAATTCTTCGGAAAGAGATTGGTACAGCTTAGTGGCG

GACGGGTGAGTAACGCGTGAGTAACCTGCCTTTCAGAGGGGGATAACGTTTGGAAAC

GAACGCTAATACCGCATAACATATTAAATTCGCATGGATTTGATATCAAAGGAGCAA

TCCGCTGAAAGATGGACTCGCGTCCAATTAGCTAGTTGGTGAGGTAACGGCCCACCA

AGGCGACGATTGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCT

GATGCAGCGACGCCGAGTGAGGGAAGAAGGTTTTCGGATTGTAAACCTCTGTCCTTG

GTGAAGATAATGACGGTAGCCAAGGAGGAAGCTACGGCTAACTACGTGCCAGCAGCC

GCGGTAATACGTAGGTAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTA

GGCGGGATTGCAAGTTGAATGTCAAATCTACGGGCTTAACCCGTAGCCGCGTTCAAA

ACTGCAGTTCTTGAGTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATG

CGTAAATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACG

CTGAGGCTCGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTG

TAAACGATGATTACTAGGTGTNNNNNNNACTGACCCCTTCCGTGCCGGAGTTAACAC

AATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACG

GGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTT

ACCAGGTCTTGACATCGTGCGCATAGCCTAGAGATAGGTGAAGCCCTTCGGGGCGCA

TAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCC

GCAACGAGCGCAACCCTTACGTTTAGTTGCTACGCAAGAGCACTCTAGACGGACTGC

CGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACC

TGGGCTACACACGTACTACAATGGCTATTAACAGAGGGAAGCAAGATGGTGACATGG

AGCAAACCCCTAAAAATAGTCTCAGTTCGGATTGCAGGCTGCAACCCGCCTGCATGA

AGCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCC

TTGTACACACCGCCCGTCACACCATGAGAGTTGGCAACACCCGAAGCCGATAGTCTA

ACCGCAAGGGGGACGTCGTCGAAGGTGGGGTTGATGATTGGGGTGAAGTCGTAACAA

GGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 39)

GCF_900155735

Intestinibacillus

TAGTGGCGGACGGGTGAGTAACGCGTGAGCAATCTGCCTTTAGGAGGGGGATAACGA

massiliensis

CCGGAAACGGTCGCTAATACCGCATGAAGTGCCGGGTGGGCATCCACCTGGCACCAA

AGGAGCAATCCGCCTTTAGATGAGCTCGCGTCCCATTAGCTAGTTGGTGAGGTAACG

GCCCACCAAGGCGACGATGGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGAC

TGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCGCAATGGGG

GAAACCCTGACGCAGCAACGCCGCGTGATTGAAGAAGGCCTTCGGGTTGTAAAGATC

TTTAATGAGGGACGAAAAATGACGGTACCTCAAGAATAAGCTCCGGCTAACTACGTG

CCAGCAGCCGCGGTAATACGTAGGGAGCAAGCGTTATCCGGATTTACTGGGTGTAAA

GGGCGAGTAGGCGGGCTGGCAAGTTGGGAGTGAAATCCGGGGGCTTAACCCCCGAAC

TGCTTTCAAAACTGCTGGCCTTGAGTGATGGAGAGGCAGGCGGAATTCCGTGTGTAG

CGGTGAAATGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGAC

ATTAACTGACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGT

AGTCCACGCCGTAAACGATGGATACTAGGTGTGGGAGGTATTGACCCCTTCCGTGCC

GGAGTTAACACAATAAGTATCCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAA

AGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACG

CGAAGAACCTTACCAGGTCTTGACATCCCTCTGACCGGTACAGAGATGTACCTTCCCT

TCGGGGCAGGGGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTG

GGTTAAGTCCCGCAACGAGCGCAACCCTTATTGTTAGTTGATACATTCAGTTGATCAC

TCTAGCGAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCA

TGCCCCTTATGACCTGGGCTACACACGTACTACAATGGCAGTCATACAGAGGGAAGC

AAAGCCGCGAGGTGGAGCAAATCCCTAAAAGCTGTCCCAGTTCAGATTGCAGGCTGC

A (SEQ ID NO: 40)

GCF_900167205

Eubacterium

TGTACCAAAGCTATTGCGCTGAAGGATGGGCTCGCGTCTGATTAGATAGTTGGTGGGG

coprostanoligenes

TAACGGCCTACCAAGTCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATT

GGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACA

ATGGGCGCAAGCCTGATGCAGCAACGCCGCGTGGAGGAAGACGGTTTTCGGATTGTA

AACTCCTGTTCTTAGTGAAGAAAAATGACGGTAGCTAAGGAGCAAGCCACGGCTAAC

TACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGAATTACTGGG

TGTAAAGGGAGCGCAGGCGGGGGAGCAAGTCAGCTGTGAAATCTATGGGCTTAACCC

ATAAACTGCAGTTGAAACTGTTCTTCTTGAGTGAAGTAGAGGTTGGCGGAATTCCGAG

TGTAGCGGTGAAATGCGTAGATATTCGGAGGAACACCGGTGGCGAAGGCGGCCAACT

GGGCTTTTACTGACGCTGAGGCTCGAAAGTGTGGGGAGCAAACAGGATTAGATACCC

TGGTAGTCCACACTGTAAACGATGATAACTAGGTGTAGGGGGTCTGACCCCTTCTGTG

CCGCAGCTAACGCAATAAGTTATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTC

AAAGGAATTGACGGGGACCCGCACAAGCAGTGGATTATGTGGTTTAATTCGATGCAA

CGCGAAGAACCTTACCAGCACTTGACATCCAACTAACGAAATAGAGATATATTAGGT

GCCCCTCGGGGAAAGTTGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGA

GATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTGCCATTAGTTGCTACGCAAGA

GCACTCTAATGGGACCGCTACCGACAAGGTGGAGGAAGGTGGGGATGACGTCAAATC

ATCATGCCCCTTATGTGCTGGGCTACACACGTAATACAATGGTCGTTAACAAAGAGA

AGCAATACCGCGAGGTGGAGCAAAACTTCAAAAACGATCTCAGTTCGGACTGTAGGC

TGAAACTCGCCTGCACGAAGTTGGAATTGCTAGTAATCGTGGATCAGCATGCCACGG

TGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGCCGGTAATAC

CCGAAGTCAGTAGTCTAACCTTAATGGAGGACGCTGCCGAAGGTAGGATTGGCGACT

GGGGTGAAGTCGTAACAAGGTAGCCGTAGGAGAACCTGCGGCTGGATCACCTCCTTT

(SEQ ID NO: 41)

GCF_900169495

Provencibacterium

CTAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

massiliense

GTCGAACGGAGAAATGCTGAGCTTGCTTTGCATTTTTTAGTGGCGGACGGGTGAGTAA

CACGTGAGCAACCTGCCTTTGTGAGGGGAATAACGTCTGGAAACGGACGCTAATACC

GCATAACGTCAAGGAACCGCATGGTTTTTTGACCAAAGATTTTATCGCAAAAAGATG

GGCTCGCGGCTGATTAGCTAGTTGGCGGGGTAACGGCCCACCAAGGCGACGATCAGT

AGCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTA

CGGGAGGCAGCAGTGGGGGATATTGCACAATGGGGGAAACCCTGATGCAGCGACGC

CGCGTGAGGGAAGACGGTTTTCGGATTGTAAACCTCTGTCTTCAGGGACGAAATCAA

TGACGGTACCTGAGGAGGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATAC

GTAGGTGGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGAATG

CAAGTTGAATGTTTAAACTATCGGCTCAACTGATAATCGCGTTCAAAACTGCATTTCT

TGAGTGGAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTA

GGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTCTAACTGACGCTGAGGCTCGA

AAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAT

TACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAATCC

ACCTGGGGAGTACGGTCGCAAGACTGAAACTCAAAGGAATTGACGGGGGCCCGCAC

AAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTG

ACATCGTGCGCATACCGTAGAGATACGGGAAGTCCTTCGGGACGCATAGACAGGTGG

TGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGC

AACCCTTATTATTAGTTGCTACGCAAGAGCACTCTAATGAGACTGCCGTTGACAAAAC

GGCGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACAC

GTACTACAATGGCACTTAACAGAGGGAAGCAAGACCGCGAGGTGGAGCAAACCCCC

AAAAAGTGTCTCAGTTCGGATTGCAGGCTGCAACCCGCCTGTATGAAGTCGGAATTG

CTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCG

CCCGTCACACCATGAGAGCCGGTAACACCCGAAGTCAGTAGCCTAACCGCAAGGAGG

GCGCTGCCGAAGGTGGGATTGGTGATTAGGGTGAAGTCGTAACAAGGTAGCCGTATC

GGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 42)

GCF_900176335

Papillibacter

TATTGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

cinnamivorans

AGTCGAACGAAAATACCAAAGCAGCAATGCGGGGGTATTTTAGTGGCGGACGGGTGA

GTAACGCGTGAGCAATCTGCCTTTTGGAGGGGGATACCGACTGGAAACGGTCGTTAA

TACCGCATAACGTATATGGACGACATCGTCCGTATACCAAAGGAGCAATCCGCCGAA

AGATGAGCTCGCGTCTGATTAGCTAGTTGGCGGGGTAAAGGCCCACCAAGGCGACGA

TCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGATACGGCCCAGAC

TCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGAAAGCCTGACCCAGCA

ACGCCGCGTGAAGGAAGAAGGCCTTCGGGTTGTAAACTTCTTTGACCAGGGAAGAAG

AAGTGACGGTACCTGGAAAACAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAA

TACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGTGTAGGCGGGA

TTGCAAGTCAGATGTGAAATGCCGGGGCTTAACCCCGGAGCTGCATTTGAAACTGTA

GTTCTTGAGTGATGGAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGA

TATTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGACATTAACTGACGCTGAGG

CGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACG

ATGGATACTAGGTGTGGGAGGTCTGACCCCTTCCGTGCCGGAGTTAACACAATAAGT

ATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCC

GCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGA

TTTGACATCCTACTAACGAGGTAGAGATACGTCAGGTGCCCTTCGGGGAAAGTAGAG

ACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCA

ACGAGCGCAACCCTTATTGCTAGTTGCTACGCAAGAGCACTCTAGCGAGACTGCCGTT

GACAAAACGGAGGAAGGCGGGGACGACGTCAAATCATCATGCCCCTTATGTCCTGGG

CTACACACGTACTACAATGGCGGTTAACAGAGGGAAGCAAGACAGTGATGTGGAGCA

AATCCCTAAAAACCGTCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAGTC

GGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTA

CACACCGCCCGTCACACCATGAGAGTCGGGAATACCCGAAGTCCGTAGTCTAACCGC

AAGGGGGACGCGGCCGAAGGTAGGTTCGATAATTGGGGTGAAGTCGTAACAAGGTA

GCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 43)

GCF_900176635

Clostridium merdae
TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCATGCCTAACACATGCA

AGTCGAACGGAGTAAGAGAGAAGCTTGCTTAGCTCTTACTTAGTGGCGGACGGGTGA

GTAACGCGTGAGTAACCTGCCTTTCAGAGGGGGATAACGTTCTGAAAAGAACGCTAA

TACCGCATAACATATTGGTGTCGCATGGCACTGGTATCAAAGGAGCAATCCGCTGAA

AGATGGACTCGCGTCCGATTAGCTAGTTGGTGGGGTAAAGGCCTACCAAGGCGACGA

TCGGTAGCCGGGTTGAGAGACTGAACGGCCACATTGGGACTGAGACACGGCCCAGAC

TCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGGCGAAAGCCTGATGCAGCA

ATGCCGCGTGAGGGAAGACGGTTTTCGGATTGTAAACCTCTGTCCTTGGTGAAGATAA

TGACGGTAGCCAAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATAC

GTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGCTCTTT

AAGTCGGGCGTGAAAGCTGTGGGCTCAACCCACAAATTGCGTTCGAAACTGGAGAGC

TTGAGTGAAGTAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGAGATC

GGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCTTTAACTGACGCTGAGGCACG

AAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGA

TTACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAATCC

ACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCAC

AAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTG

ACATCCAACTAACGAAGCAGAGATGCATTAGGTGCCCTTCGGGGAAAGTTGAGACAG

GTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGA

GCGCAACCCCTGTGATTAGTTGCTACGCAAGAGCACTCTAATCAGACTGCCGTTGACA

AAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTAC

ACACGTACTACAATGGTCGCTAACAGAGGGAAGCCAAGCCGCGAGGTGGAGCAAAC

CCCCAAAAGCGGTCTCAGTTCGGATTGTAGGCTGCAACCCGCCTACATGAAGTTGGA

ATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACAC

ACCGCCCGTCACACCATGGGAGCCGGTAATACCCGAAGCCAATAGTCTAACCGCAAG

GAGGACGTTGTCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCG

TATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 44)

GCF_900186535

Marasmitruncus

AAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAAGT

massiliensis

CGAACGGACAGAAGAGAAGCTTGCTTAGCTTCTGTTAGTGGCGGACGGGTGAGTAAC

ACGTGAGTAACCTGCCTTTCAGAGGGGGATAACGATTGGAAACGATCGCTAATACCG

CATGATGTTGCGATGGGACATCCTATTGCAACCAAAGGAGTAATCCGCTGAAAGATG

GGCTCGCGGCCGATTAGATAGTTGGTGAGGTAACGGCCCACCAAGTCAGCGATCGGT

AGCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTA

CGGGAGGCAGCAGTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCGACGC

CGCGTGAGGGAAGACGGTCTTCGGATTGTAAACCTCTGTCTTAGGGGAAGAAAATGA

CGGTACCCTAAGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTA

GGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGGCAGCA

AGTTGGATGTTTAAACTACCGGCTTAACCGGTAACTGCATCCAAAACTGCAGTTCTTG

AGTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGG

AGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACGCTGAGGCTCGAAA

GCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGATTA

CTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCAC

CTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAA

GCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGAC

ATCGTGCGCATACCATAGAGATATGGGAAGCCCTTCGGGGCGCATAGACAGGTGGTG

CATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAA

CCCTTATTACTAGTTGCTACGCAAGAGCACTCTAGTGAGACTGCCGTTGACAAAACGG

AGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGT

ACTACAATGGCACTTAAACAGAGGGCTGCTACATCGCGAGATGAAGCGAATCCCGAA

AAAGTGTCTCAGTTCGGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATTGCTA

GTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCC

GTCACACCATGGGAGTCGGTAACACCCGAAGCCAGTAGTCTAACCGCAAGGGGGACG

CTGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGA

AGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 45)

GCF_900186585

Massilimaliae

TAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGTCGGCGCGCCTAACACATGCAAG

timonensis

TCGAACGAAGTTGCTTTGAATGAATTCTTCGGAAGGAATTTGATTCAACTTAGTGGCG

GACGGGTGAGTAACGCGTGAGTAACCTGCCTTTCAGAGGGGGATAACGTCTGGAAAC

GGACGCTAATACCGCATAACATATTGGTTTCGCATGGAGCTGATATCAAAGGAGCAA

TCCGCTGAAAGATGGACTCGCGTCCAATTAGCTAGTTGGTGAGGTAACGGCCCACCA

AGGCGACGATTGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCT

GATGCAGCGACGCCGAGTGAGGGAAGAAGGTTTTCGGATTGTAAACCTCTGTCCTTG

GTGAAGATAATGACGGTAACCAAGGAGGAAGCTACGGCTAACTACGTGCCAGCAGCC

GCGGTAATACGTAGGTAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTA

GGCGGGATTGCAAGTTGAATGTTAAATCTATGGGCTCAACCCATAGCCGCGTTCAAA

ACTGCAGTTCTTGAGTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATG

CGTAAATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACG

CTGAGGCTCGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTG

TAAACGATGATTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGGAGTTAACACA

ATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGG

GGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTA

CCAGGTCTTGACATCCGGTGCATAGCCTAGAGATAGGTGAAGCCCTTCGGGGCACCG

AGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCG

CAACGAGCGCAACCCTTACGTTTAGTTGCTACGCAAGAGCACTCTAGACGGACTGCC

GTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCT

GGGCTACACACGTACTACAATGGCTATTAACAGAGGGAAGCAAGATGGTGACATGGA

GCAAACCCCTAAAAATAGTCTCAGTTCGGATTGCAGGCTGCAACCCGCCTGCATGAA

GCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTT

GTACACACCGCCCGTCACACCATGAGAGTTGGCAACACCCGAAGCCGATAGTCTAAC

CGCAAGGGGGACGTCGTCGAAGGTGGGGTTGATGATTGGGGTGAAGTCGTAACAAGG

TAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 46)

GCF_900199435

Pygmaiobacter

ATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

massiliensis

GTCGAACGGAGCTTGCACTTCTGAAGTTTTCGGATGGACGAGGTACAAGCTTAGTGG

CGAACGGGTGAGTAACACGTGAAGAACCTGCCCTTCAGTGGGGGACAACAGTTGGAA

ACGACTGCTAATACCGCATAAGACCACAGTACCGCATGGTACAGTGATCAAAGGATT

TATTCGCTGAAGGATGGCTTCGCGTCCGATTAGGTAGTTGGTGAGGTAACGGCCCACC

AAGCCTACGATCGGTAGCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACA

CGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGAGGAAACTC

TGATGCAGCGACGCCGCGTGAGGGAAGAAGGTCTTCGGATTGTAAACCTCTGTCTTC

AGGGACGATAATGACGGTACCTGAGGAGGAAGCACCGGCTAACTACGTGCCAGCAG

CCGCGGTAAAACGTAGGGTGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCG

CAGGCGGGAAGATAAGTTGGATGTTTAATCTACGGGCTCAACCCGTATCAGCATTCA

AAACTATTTTTCTTGAGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAAT

GCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACTAACTGAC

GCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCC

GTAAACGATGATTACTAGGTGTGGGAGGATTGACCCCTTCCGTGCCGCAGTTAACAC

AATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACG

GGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTT

ACCAGGTCTTGACATCCCGTGCATAGTGTAGAGATACATGAAGTCCTTCGGGACACG

GTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCC

GCAACGAGCGCAACCCTTATTGCTAGTTACTACGAAAGAGGACTCTAGCAAGACTGC

CGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACC

TGGGCCACACACGTACTACAATGGCTATTAACAAAGAGATGCTAAGCCGCGAGGTGG

AGCGAACCTCATAAAAATAGTCTCAGTTCGGATTGCAGGCTGCAACTCGCCTGCATG

AAGCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGC

CTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCAGTAGTCT

AACCGCAAGGAGGACGCTGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAAC

AAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 47)

GCF_900240385

Clostridium

TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCATGCCTAACACATGCA

minihomine

AGTCGAACGGAGTAAGAGATAAGCTTGCTTAACTCTTACTTAGTGGCGGACGGGTGA

GTAACGCGTGAGTAACCTGCCTTTCAGAGGGGGATAACGTTCTGAAAAGAACGCTAA

TACCGCATGATATATCGGTGTCGCATGGCACTGATATCAAAGGAGCAATCCGCTGAA

AGATGGACTCGCGTCCGATTAGCCAGTTGGCGGGGTAATGGCCCACCAAAGCGACGA

TCGGTAGCCGGGTTGAGAGACTGGACGGCCACATTGGGACTGAGACACGGCCCAGAC

TCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCA

ATGCCGCGTGAGGGAAGACGGTCTTCGGATTGTAAACCTCTGTCCTTGGTGAAGATA

ATGACGGTAGCCAAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATA

CGTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGCTTTT

CAAGTCGGGCGTGAAAGCTGTGGGCTTAACCCACAAATTGCGTTCGAAACTGGAGAG

CTTGAGTGAAGTAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGAGAT

CGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCTTTAACTGACGCTGAGGCAC

GAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATG

ATTACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAATC

CACCTGGGGAGTACGGCCGCAAGGCTGAAACTCAAAGGAATTGACGGGGGCCCGCA

CAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTT

GACATCCAACTAACGAAGCAGAGATGCATTAGGTGCCCTTCGGGGAAAGTTGAGACA

GGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACG

AGCGCAACCCCTGTGATTAGTTGCTACGCAAGAGCACTCTAATCAGACTGCCGTTGAC

AAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTA

CACACGTACTACAATGGTCGTTAACAACGGGAAGCTAAGCCGCGAGGTGGCGCAAAT

CCCCAAAAACGGTCTCAGTTCGGATTGTAGGCTGCAACCCGCCTACATGAAGTTGGA

ATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACAC

ACCGCCCGTCACACCACGGGAGCCGGTAATACCCGAAGCCGATAGTCTAACCGCAAG

GAGGACGTCGTCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCG

TATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 48)

GCF_900289145

Neobitarella

TAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCTTAACACATGCAAG

massiliensis

TCGAACGGACACATCCGACGGAATAGCTTGCTAGGAAGATGGATGTTGTTAGTGGCG

GACGGGTGAGTAACACGTGAGCAACCTACCTCAGAGTGGGGGACAACAGTTGGAAA

CGACTGCTAATACCGCATAAGATGGCAGGGTCGCATGGCCTGGTCATAAAAGGAGCA

ATTCGCTCTGAGATGGGCTCGCGTCTGATTAGCTAGTTGGTGAGGTAACGGCTCACCA

AGGCAACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCT

GATGCAGCGACGCCGCGTGAGGGAAGACGGTTTTCGGATTGTAAACCTCTGTCTTGTG

GGACGATAGTGACGGTACCACAGGAGGAAGCCATGGCTAACTACGTGCCAGCAGCCG

CGGTAATACGTAGATGGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGTGTAG

GCGGGCTGGTAAGTTGAATGTGAAACCTTCGGGCTCAACCCGGAGCGTGCGTTCAAA

ACTGCTGGTCTTGAGTGAAGTAGAGGCAGGCGGAATTCCCGGTGTAGCGGTGGAATG

CGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTTACTGACG

CTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCG

TAAACGATGATTACTAGGTGTGGGGGGATTGACCCCCTCCGTGCCGGAGTTAACACA

ATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGG

GGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAAAACCTTA

CCAGGTCTTGACATCCATCGCCAGGCTAAGAGATTAGCTGTTCCCTTCGGGGACGATG

AGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCG

CAACGAGCGCAACCCTTACTATTAGTTGCTACGCAAGAGCACTCTAATGGGACTGCC

GTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCT

GGGCTACACACGTACTACAATGGCCGTTAACAGAGAGCAGCGATACCGCGAGGTGGA

GCGAATCTAGAAAAACGGTCTCAGTTCGGATTGCAGGCTGAAACTCGCCTGCATGAA

GTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTT

GTACACACCGCCCGTCACACCATGAGAGCCGGTAACACCCGAAGTCAGTAGCCTAAC

CGCAAGGAGGGCGCTGCCGAAGGTGGGGCTGGTAATTGGGGTGAAGTCGTAACAAG

GTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 49)

GCF_000154385

Faecalibacterium

TATAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCA

prausnitzii

AGTCGAACGAGCGAGAGAGAGCTTGCTTTCTTGAGCGAGTGGCGAACGGGTGAGTAA

CGCGTGAGGAACCTGCCTCAAAGAGGGGGACAACAGTTGGAAACGACTGCTAATACC

GCATAAGCCCACGGCTCGGCATCGAGCAGAGGGAAAAGGAGCAATCCGCTTTGAGAT

GGCCTCGCGTCCGATTAGCTGGTTGGTGAGGTAACGGCCCACCAAGGCGACGATCGG

TAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCT

ACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACG

CCGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCTGTTGTTGAGGAAGATAATG

ACGGTACTCAACAAGGAAGTGACGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGT

AGGTCACAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGGAAGAC

AAGTTGGAAGTGAAATCCATGGGCTCAACCCATGAACTGCTTTCAAAACTGTTTTTCT

TGAGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCG

GGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGCTCG

AAAGTGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACACTGTAAACGATGA

TTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACACAATAAGTAATCC

ACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCAC

AAGCAGTGGAGTATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGTCTTG

ACATCCCTTGACGATGCTGGAAACAGTATTTCTCTTCGGAGCAAGGAGACAGGTGGT

GCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCA

ACCCTTATGGTCAGTTACTACGCAAGAGGACTCTGGCCAGACTGCCGTTGACAAAAC

GGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACTTGGGCTACACAC

GTACTACAATGGCGTTAAACAAAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCA

GAAACAACGTCCCAGTTCGGACTGCAGGCTGCAACTCGCCTGCACGAAGTCGGAATT

GCTAGTAATCGCAGATCAGCATGCTGCGGTGAATACGTTCCCGGGCCTTGTACACACC

GCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAG

GACGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAGGTAGCCGTAG

GAGAACCTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 50)

GCF_000174895

Ruminococcus

TAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCTTAACACATGCAAG

flavefaciens

TCGAACGGAGATAATTTGAGTTTACTTGGATTATCTTAGTGGCGGACGGGTGAGTAAC

ACGTGAGCAACCTGCCTTTGAGAGAGGGATAGCTTCTGGAAACGGATGGTAATACCT

CATAACATAATTGAAGGGCATCCTTTAATTATCAAAGATTTATCACTCAAAGATGGGC

TCGCATCTGATTAGATAGTTGGTGAGGTAACGGCTCACCAAGTCGACGATCAGTAGC

CGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGG

GAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGATGCCGC

GTGGAGGAAGAAGGTTTTCGGATTGTAAACTCCTGTCTTAAAGGACGATAATGACGG

TACTTTAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGG

AGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGATTGCAAGTC

AGATGTGAAATACATGGGCTCAACCCATGGGCTGCATTTGAAACTGTAGTTCTTGAGT

GAAGTAGAGGTAAGCGGAATTCCTGGTGTAGCGGTGAAATGCGTAGATATCAGGAGG

AACACCGGTGGCGAAGGCGGCTTACTGGGCTTTTACTGACGCTGAGGCTCGAAAGCG

TGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGATTACTA

GGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCTG

GGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCA

GTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATC

GTATGCATAACTTAGAGATAAGTGAAATCCCTTCGGGGACATATAGACAGGTGGTGC

ATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAAC

CCTTACCTTTAGTTGCTACGCAAGAGCACTCTAAAGGGACTGCCGTTGACAAAACGG

AGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGT

ACTACAATGGCAATTAACAAAGAGAAGCAAGACAGCGATGTGGAGCAAATCTCGAA

AAATTGTCCCAGTTCAGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATTGCTA

GTAATCGTGGATCAGCATGCCACGGTGAATACGTTCCCGGGCCTTGTACACACCGCCC

GTCACACCATGGGAGTCGGTAACACCCGAAGTCGGTAGTCTAACAGCAATGAGGACG

CCGCCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGA

AGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 51)

GCF_000177015

Ruminococcaceae

TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

bacterium D16
GTCGAACGGAGTGCCTTTGAAAGAGGATTCGTCCAATTGATAAGGTTACTTAGTGGCG

GACGGGTGAGTAACGCGTGAGGAACCTGCCTTGGAGTGGGGAATAACACAGTGAAA

ATTGTGCTAATACCGCATAATGCAGTTGGGCCGCATGGCTCTGACTGCCAAAGATTTA

TCGCTCTGAGATGGCCTCGCGTCTGATTAGCTAGTTGGTGGGGTAACGGCCCACCAAG

GCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTGA

CCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTCTTAGGG

ACGAAGCAAGTGACGGTACCTAAGGAATAAGCCACGGCTAACTACGTGCCAGCAGCC

GCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTGTA

GGCGGGATTGCAAGTCAGATGTGAAAACCACGGGCTCAACCTGTGGCCTGCATTTGA

AACTGTAGTTCTTGAGTACTGGAGAGGCAGACGGAATTCCTAGTGTAGCGGTGAAAT

GCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGTCTGCTGGACAGCAACTGAC

GCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCT

GTAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGCAGTTAACAC

AATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGACG

GGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTT

ACCAGGGCTTGACATCCCGAGGCCCGGTCTAGAGATAGACCTTTCTCTTCGGAGACCT

CGGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTC

CCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAGACT

GCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGT

CCTGGGCCACACACGTACTACAATGGTGGTTAACAGAGGGAGGCAATACCGCGAGGT

GGAGCAAACCCCTAAAAGCCATCCCAGTTCGGATTGCAGGCTGCAACCCGCCTGCAT

GAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGG

CCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTAGCC

TAACCGCAAGGGGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCGTAAC

AAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 52)

GCF_000178155

Ruminococcus albus
GGCCCACCAAGCCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGA

CTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGG

CGAAAGCCTGATGCAGCGATGCCGCGTGAGGGAAGAAGGTTTTAGGATTGTAAACCT

CTGTCTTCGGGGACGATAATGACGGTACCCGAGGAGGAAGCTCCGGCTAACTACGTG

CCAGCAGCCGCGGTAATACGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAA

GGGAGCGTAGGCGGGACTGCAAGTCAGGTGTGAAATGTAGGGGCTTAACCCCTACCC

TGCACTTGAAACTGTGGTTCTTGAGTGAAGTAGAGGTAAGCGGAATTCCTAGTGTAGC

GGTGAAATGCGTAGATATTAGGAGGAACATCAGTGGCGAAGGCGGCTTACTGGGCTT

TAACTGACGCTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAG

TCCACGCCGTAAACGATGATTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCA

GTTAACACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGG

AATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGA

AGAACCTTACCAGGTCTTGACATCGTGAGCATAGCTTAGAGATAAGTGAAATCCCTTC

GGGGACTCATAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGG

TTAAGTCCCGCAACGAGCGCAACCCTTACTGTTAGTTGCTACGCAAGAGCACTCTAGC

AGGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCC

TTATGACCTGGGCTACACACGTACTACAATGGCTGTTAACAGAGGGAAGCAAAGCAG

TGATGCAGAGCAAAACCCTAAAAGCAGTCTTAGTTCGGATTGTAGGCTGCAACCCGC

CTACATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTT

CCCGGGCCTTGTACACACCGCCCGTCACGCCATGGGAGTCGGTAACACCCGAAGCCT

GTGTTCTAACCGCAAGGAGGAAGCAGTCGAAGGTGGGATTGATGACTGGGGTGAAGT

CGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 53)

GCF_000403395

Anaerotruncus sp
AGATGGGCTCGCGGCCGATTAGCTAGTTGGTGGGGCAACGGCCCACCAAGGCGACGA

G3 2012
TCGGTAGCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAGAC

TCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCG

ACGCCGCGTGAGGGAAGACGGTCTTCGGATTGTAAACCTCTGTCTTTGGGGAAGAAA

ATGACGGTACCCAAAGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATA

CGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGCGA

GAAAGTTGAATGTTAAATCTACCGGCTTAACTGGTAGCTGCGTTCAAAACTTCTTGTC

TTGAGTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATT

AGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACGCTGAGGCTCG

AAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGA

TTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCC

ACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCAC

AAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTG

ACATCGTGCGCATAGCCTAGAGATAGGTGAAGCCCTTCGGGGCGCACAGACAGGTGG

TGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGC

AACCCTTATTATTAGTTGCTACGCAAGAGCACTCTAATGAGACTGCCGTTGACAAAAC

GGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACAC

GTACTACAATGGCACTGAAACAGAGGGAAGCGACATCGCGAGGTGAAGCGAATCCC

AAAAAAGTGTCCCAGTTCGGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATT

GCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACC

GCCCGTCACACCATGGGAGTCGGTAACACCCGAAGCCAGTAGCCTAACCGCAAGGAG

GGCGCTGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTAT

CGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 54)

GCF_000403435

Oscillibacter sp 1 3
TATAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCTTAACACATGCA

AGTCGAACGGAGCACCCCTGAAGGAGTTTTCGGACAACGGAAGGGAATGCTTAGTGG

CGGACTGGTGAGTAACGCGTGAGGAACCTGCCTTCCAGAGGGGGACAACAGTTGGAA

ACGACTGCTAATACCGCATGAAACATTTGAACCGCATGGTTTGAATGTCAAAGATTTA

TCGCTGGAAGATGGCCTCGCGTCTGATTAGCTAGTAGGCGGGGTAACGGCCCACCTA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGATACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTAAGAG

GGAAGAGAAGAAGACGGTACCTCTTGAATAAGCCACGGCTAACTACGTGCCAGCAGC

CGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGTGC

AGCCGGGAAGACAAGTCAGATGTGAAATCCCGCGGCTCAACCGCGGAACTGCATTTG

AAACTGTTTTTCTTGAGTACCGGAGAGGTCATCGGAATTCCTTGTGTAGCGGTGAAAT

GCGTAGATATAAGGAAGAACACCAGTGGCGAAGGCGGATGACTGGACGGCAACTGA

CGGTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGC

TGTAAACGATGGATACTAGGTGTGCGGGGACTGACCCCCTGCGTGCCGCAGTTAACA

CAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGAC

GGGGGCCCGCACAAGCGGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAGAACCT

TACCAGGGCTTGACATGGAGAGGACCGCTCTAGAGATAGGGTTTTCCCTTCGGGGAC

CTCTCACACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAG

TCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAGA

CTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTAT

GTCCTGGGCTACACACGTAATACAATGGCGGTCAACAGAGGGATGCAAATCCGCGAG

GAGGAGCGAACCCCCAAAAGCCGTCCCAGTTCGGATCGCAGGCTGCAACCCGCCTGC

GTGAAGTCGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCG

GGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTAG

CCTAACAGCAATGAGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCGTA

ACAAGGTAGCCGTTCGAGAACGAGCGGCTGGATCACCTCCTTT (SEQ ID NO: 55)

GCF_000421005

Clostridiales

ATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGACGATCAGTAGCCGGACTGAG

bacterium NK3B98
AGGTTGACCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCA

GTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCAACGCCGCGTGAGTGATG

ACGGCCTTCGGGTTGTAAAGCTCTGTCTTCAGGGACGATAATGACGGTACCTGAGGA

GGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCGAGCGTT

ATCCGGATTTACTGGGCGTAAAGGATGCGTAGGTGGAATTTTAAGTGGGATGTGAAA

TACCCGGGCTCAACCTGGGAACTGCATTCCAAACTGGAATTCTAGAGTGCAGGAGAG

GAAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGAGATTAGGAAGAACACCAGT

GGCGAAGGCGGCTTGCTGGACAGTAACTGACGCTAAGGCGCGAAAGCGTGGGGAGC

AAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGGGTACTAGGTGTAGG

GGTTTCGATACCTCTGTGCCGCCGTAAACACAATAAGTACCCCGCCTGGGGAGTACG

GTCGCAAGATTAAAACTCAAAGGAATTGACGGGGGCCCGCACAAGTAGCGGAGCAT

GTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCCGGCGACC

GGTGTAGAGATACACCTTCTTCTTCGGAAGCGCCGGTGACAGGTGGTGCATGGTTGTC

GTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATAGT

TAGTTGCTAACAGTAAGATGAGCACTCTAGCTAGACTGCCGTGGTTAACGCGGAGGA

AGGTGGGGATGACGTCAAATCATCATGCCCCTTATGTCTAGGGCTACACACGTGCTAC

AATGGCGAGAACAAAGAGAAGCAAGACCGCGAGGTGGAGCAAAACTCATAAAACTC

GTCCCAGTTCGGATTGCAGGCTGAAACCCGCCTGTATGAAGTTGGAATCGCTAGTAAT

CGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAC

ACCATGAGAGTCGGGAACACCCGAAGTCCGTAGCCTAACCGCAAGGGGGGCGCGGC

CGAAGGTGGGTTCGATAATTGGGGTGAAGTCGTAACAAGGTAGCCGT (SEQ ID NO: 56)

GCF_000469425

Oscillibacter sp
TATAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCTTAACACATGCA

KLE 1728
AGTCGAACGGAGCACCCTTGACTGAGGTTTCGGCCAAATGATAGGAATGCTTAGTGG

CGGACTGGTGAGTAACGCGTGAGGAACCTACCTTCCAGAGGGGGACAACAGTTGGAA

ACGACTGCTAATACCGCATGACGCATGACCGGGGCATCCCGGGCATGTCAAAGATTT

TATCGCTGGAAGATGGCCTCGCGTCTGATTAGCTAGATGGTGGGGTAACGGCCCACC

ATGGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGATA

CGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGACGCAAGTC

TGACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTGTCA

GGGAAGAGTAGAAGACGGTACCTGACGAATAAGCCACGGCTAACTACGTGCCAGCA

GCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGT

GCAGCCGGGCCGGCAAGTCAGATGTGAAATCTGGAGGCTTAACCTCCAAACTGCATT

TGAAACTGTAGGTCTTGAGTACCGGAGAGGTTATCGGAATTCCTTGTGTAGCGGTGAA

ATGCGTAGATATAAGGAAGAACACCAGTGGCGAAGGCGGATAACTGGACGGCAACT

GACGGTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCA

CGCTGTAAACGATGGATACTAGGTGTGCGGGGACTGACCCCCTGCGTGCCGCAGTTA

ACACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATT

GACGGGGGCCCGCACAAGCGGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAGAA

CCTTACCAGGGCTTGACATCCTACTAACGAAGTAGAGAT (SEQ ID NO: 57)

GCF_000492175

Firmicutes bacterium
TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

ASF500
GTCGAACGGAGGACCCCTGAAGGAGTTTTCGGACAACTGAAGGGAATCCTTAGTGGC

GGACGGGTGAGTAACGCGTGAGTAACCTGCCTTGGAGTGGGGAATAACAGCTGGAAA

CAGCTGCTAATACCGCATGATATGTCTGTGTCGCATGGCACTGGACATCAAAGATTTA

TCGCTCTGAGATGGACTCGCGTCTGATTAGCTAGTTGGCGGGGTAACGGCCCACCAA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTCTCAGG

GACGAAGCAAGTGACGGTACCTGAGGAATAAGCCACGGCTAACTACGTGCCAGCAGC

CGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTGT

AGGCGGGACTGCAAGTCAGATGTGAAAACCACGGGCTCAACCTGTGGCCTGCATTTG

AAACTGTAGTTCTTGAGTACTGGAGAGGCAGACGGAATTCCTAGTGTAGCGGTGAAA

TGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGTCTGCTGGACAGCAACTGA

CGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGC

TGTAAACGATGGATACTAGGTGTGGGGGGACTGACCCCCTCCGTGCCGCAGTTAACA

CAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGAC

GGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCT

TACCAGGGCTTGACATCCCGGCGACCGGTGTAGAGATACACTTTCTTCTTCGGAAGCG

CCGGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGT

CCCGCAACGAGCGCAACCCTTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAGACT

GCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGT

CCTGGGCCACACACGTACTACAATGGTGGTCAACAGAGGGAAGCAAAACCGCGAGGT

GGAGCAAATCCCTAAAAGCCATCCCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGT

GAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGG

CCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTAGCC

TAACAGCAATGGGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCGTAAC

AAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 58)

GCF_000621805

Ruminococcus sp
AATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCTTAACACATGCA

FC2018
AGTCGAACGGGGTTACAAGATAAGCTTGCTTAATTTGTAACCTAGTGGCGGACGGGT

GAGTAACACGTGAGCAATCTGCCCTTAAGAGGGGGATACCAGTTAGAAATGACTGTT

AATACCGCATAAGATAGTAGTACCGCATGGTACAGCTATAAAAGATTTATCGCTTAA

GGATGAGCTCGCGTCTGATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCAACGA

TCAGTAGCCGGACTGAGAGGTTGGACGGCCACATTGGGACTGAGACACGGCCCAGAC

TCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGAGGAAACTCTGATGCAGCG

ATGCCGCGTGAGGGAAGAAGGTTTTAGGATTGTAAACCTCTGTTGACAGGGACGATA

ATGACGGTACCTGTTGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATA

CGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGATC

GCAAGTCAGGTGTGAAATGCGGGGGCTCAACCCCCGAACTGCACTTGAAACTGTGGT

TCTTGAGTGAAGTAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATA

TTAGGAGGAACATCAGTGGCGAAGGCGGCTTACTGGGCTTTAACTGACGCTGAGGCT

CGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGAT

GATTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGCTAACGCAATAAGTAA

TCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGC

ACAAGCAGTGGAGTATGTGGATTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCT

TGACATCGTACGCATAGCATAGAGATATGTGAAATCCCTTCGGGGACGTATAGACAG

GTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGA

GCGCAACCCTTACTGTTAGTTGCTACGCAAGAGCACTCTAGCAGGACTGCCGTTGACA

AAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCCTC

ACACGTACTACAATGGCTGCCAACAGAGGGAAGCAAAGCAGTGATGCAGAGCAAAG

CCCCAAAAGCAGTCTTAGTTCGGATTGCAGGCTGAAACCCGCCTGCATGAAGTCGGA

ATTGCTAGTAATCGCAGATCAGCATGCTGCGGTGAATACGTTCCCGGGCCTTGTACAC

ACCGCCCGTCACGCCATGGGAGTCGGTAACACCCGAAGCCTGTAGCCCAACCGCAAG

GAGGACGCAGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCC

GTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 59)

GCF_000686125

Ruminococcus sp
TTAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCTTAACACATGCAA

NK3A76
GTCGAACGGAGTTTTAGAGAGCTTGCTTTTTAAAACTTAGTGGCGGACGGGTGAGTAA

CACGTGAGCAATCTGCCTTTCAGAGGGGGATAGCAGTTGGAAACGACTGATAATACC

GCATAATATAGTAGGATCGCATGGTTCAACTATCAAAGATTTATCGCTGAAAGATGA

GCTCGCGTCTGATTAGATAGTTGGTGAGGTAACGGCTCACCAAGTCGACGATCAGTA

GCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTAC

GGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAGCGATGCC

GCGTGAGGGAAGAAGGTTTTAGGATTGTAAACCTCTGTCTTCAGGGACGATAATGAC

GGTACCTGAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAG

GGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGTGCAGGCGGGACTGCAAG

TCAGATGTGAAATGTAGGGGCTTAACCCCTGAACTGCATTTGAAACTGTAGTTCTTGA

GTGAAGTAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGA

GGAACATCAGTGGCGAAGGCGGCTTACTGGGCTTTTACTGACGCTGAGGCTCGAAAG

CGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGATTAC

TAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCT

GGGGAGTACGGCCGCAAGGCTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGC

AGTGGAGTATGTGGATTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACAT

CGTACGCATAGCATAGAGATATGTGAAATCCCTTCGGGGACGGACAGACAGGTGGTG

CATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAA

CCCTTACTGTTAGTTGCTACGCAAGAGCACTCTAGCAGGACTGCCGTTGACAAAACGG

AGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCCTCACACGT

ACTACAATGGCTGTTAACAGAGAGAAGCGACATAGTGATATGAAGCAAAACCCTAAA

AGCAGTCTCAGTTCGGATTGCAGGCTGAAACCCGCCTGCATGAAGTCGGAATTGCTA

GTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCC

GTCACACCATGGGAGTCGGTAACACCCGAAGTCAGTAGCCTAACCGTAAGGAGGGCG

CTGCCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGA

AGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 60)

GCF_000701945

Ruminococcus

CAAAGATTTATCACTCAGAGATGGGCTCGCGTCTGATTAGATAGTTGGTGAGGTAACG

flavefaciens

GCTCACCAAGTCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGAC

TGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGG

GGAACCCTGATGCAGCGATGCCGCGTGGAGGAAGAAGGTTTTCGGATTGTAAACTCC

TGTCTTAAAGGACGATAATGACGGTACTTTAGGAGGAAGCTCCGGCTAACTACGTGC

CAGCAGCCGCGGTAATACGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAG

GGAGCGTAGGCGGGACTGCAAGTCAGATGTGAAATGCCGGGGCTTAACCCCGGAGCT

GCATTTGAAACTGTGGTTCTTGAGTGAAGTAGAGGCAAGCGGAATTCCTGGTGTAGC

GGTGAAATGCGTAGATATCAGGAGGAACACCGGTGGCGAAGGCGGCTTGCTGGGCTT

TTACTGACGCTGAGGCTCGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAG

TCCACGCTGTAAACGATGATTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAG

TTAACACAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGA

ATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAA

GAACCTTACCAGGTCTTGACATCGTATGCATAGCATAGAGATATGTGAAATCTCTTCG

GAGACATATAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGT

TAAGTCCCGCAACGAGCGCAACCCTTACCTTTAGTTGCTACGCAAGAGCACTCTAAAG

GGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCT

TATGACCTGGGCTACACACGTACTACAATGGCAATCAACAAAGAGAAGCAAGACAGT

GATGTGGAGCGAATCTCAAAAAATTGTCCCAGTTCGGATTGCAGGCTGCAACTCGCCT

GCATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCC

CGGGCCTTGTACACACCGCCCGTCACACCATGGGAGTCGGTAACACCCGAAGTCAGT

AGTCTAACAGCAATGAGGACGCTGCCGAAGGTGGGATTGATGACTGGGGTGAAGTCG

TAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 61)

GCF_000712055

Ruminococcus sp
ATAAAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCACGCCTAACACATGCAA

HUN007
GTCGAACGGAGTTTAAGAGAGCTTGCTCTTTTAAACTTAGTGGCGGACGGGTGAGTA

ACACGTGAGCAACCTGCCTTTCAGAGAGGGATAGCTTCTGGAAACGGATGGTAATAC

CTCATAACATATTGATACGGCATCGTATTGATATCAAAGATTTATCGCTGAAAGATGG

GCTCGCGTCTGATTAGCTGGTTGGTGAGGTAACGGCCCACCAAGGCAACGATCAGTA

GCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTAC

GGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAGCGATGCC

GCGTGAGGGAAGAAGGTTTTCGGATTGTAAACCTCTGTCATCGGGGACGAAAATGAC

GGTACCCGAGAAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAG

GGAGCAAGCGTTATCCGGAATTACTGGGTGTAAAGGGAGTGTAGGCGGGACTGCAAG

TCAGATGTGAAATATGCCGGCTCAACTGGCAGACTGCATTTGAAACTGTGGTTCTTGA

GTGAAGTAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGA

GGAACATCAGTGGCGAAGGCGGCTTACTGGGCTTTAACTGACGCTGAGGCTCGAAAG

CGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGATTAC

TAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCT

GGGGAGTACGGCCGCAAGGCTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGC

AGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACAT

CGAGTGAAGTATCAAGAGATTGATATGTCTTCGGACACAAAGACAGGTGGTGCATGG

TTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTT

ACCATTAGTTGCTACGCAAGAGCACTCTAATGGGACTGCCGTTGACAAAACGGAGGA

AGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTACTAC

AATGGCAATCGAACAGAGGGAAGCAATACAGCGATGTAAAGCAAAACCCGAAAAAA

TTGTCTCAGTTCGGATTGCAGGCTGCAACCCGCCTGCATGAAGTCGGAATTGCTAGTA

ATCGCAGATCAGCATGCTGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTC

ACACCATGGGAGTCGGTAACACCCGAAGCCAGTAGTCCAACCGCAAGGAGGACGCTG

TCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGG

TGCGGCTGGATCACCTCCTTT (SEQ ID NO: 62)

GCF_000752215

bacterium M54
TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

AGTCGAACGGAATTAAGTTTAACACCGAACACTTTGTTTGGTGGGGACACCTGACCG

AGTGGTGGGTGTTGAGCTTAATTTAGTGGCGGACGGGTGAGTAACGCGTGAGTAACC

TGCCTTTCAGAGGGGGATAACGTCTGGAAACGGACGCTAATACCGCATGACATATTT

GGGCTGCATGGTCTGAATATCAAAGGAGCAATCCGCTGAAAGATGGACTCGCGTCCG

ATTAGCTAGTTGGTGAGATAAAGGCCCACCAAGGCGACGATCGGTAGCCGGACTGAG

AGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCA

GTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCAACGCCGCGTGAGGGAA

GACGGTTTTCGGATTGTAAACCTCTGTCCTTGGTGACGAAACAAATGACGGTAGCCAA

GGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGAGCAAGC

GTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGCTCTGCAAGTCAGGCGTG

AAATATATGGGCTTAACCCATAGACTGCGTTTGAAACTGTGGAGCTTGAGTGAAGTA

GAGGTAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGAGATCGGGAGGAACAC

CAGTGGCGAAGGCGGCTTACTGGGCTTTAACTGACGCTGAGGCACGAAAGCATGGGT

AGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGATTACTAGGTGT

GGGGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAATCCACCTGGGGAG

TACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGA

GTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCAACTA

ACGAAGCAGAGATGCATCAGGTGCCCTTCGGGGAAAGTTGAGACAGGTGGTGCATGG

TTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCT

GTGATTAGTTGCTACGCAAGAGCACTCTAATCAGACTGCCGTTGACAAAACGGAGGA

AGGTGGGGACGACGTCAAATCATCATGCCCTTTATGACCTGGGCTACACACGTACTAC

AATGGCTGTTAACAAAGGGAAGCAAGACCGCGAGGTGGAGCAAAACCTAAAAAACA

GTCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAGTTGGAATTGCTAGTAAT

CGCGGATCATCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAC

ACCATGGGAGCCGGTAATACCCGAAGTCAGTAGCCTAACCGCAAGGGAGGCGCTGCC

GAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTG

CGGCTGGATCACCTCCTTT (SEQ ID NO: 63)

GCF_000765135

Intestinimonas

TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

butyriciproducens

GTCGAACGGAGCACCCCTGACGGAGTTTTCGGACAACGAAAGGGAATGCTTAGTGGC

GGACGGGTGAGTAACGCGTGAGTAACCTGCCTTGGAGTGGGGAATAACAGCCGGAA

ACGGCTGCTAATACCGCATGATGTATCTGGATCGCATGGTTCTGGATACCAAAGATTT

ATCGCTCTGAGATGGACTCGCGTCTGATTAGCTAGTTGGTGAGGTAATGGCTCACCAA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGAAAGCCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCCCTCGGGTTGTAAACTTCTTTTGTCAG

GGACGAAGCAAGTGACGGTACCTGACGAATAAGCCACGGCTAACTACGTGCCAGCAG

CCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTG

TAGGCGGGAGTGCAAGTCAGATGTGAAAACTATGGGCTCAACCCATAGCCTGCATTT

GAAACTGTACTTCTTGAGTGATGGAGAGGCAGGCGGAATTCCCTGTGTAGCGGTGAA

ATGCGTAGATATAGGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGACATTAACTG

ACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACG

CCGTAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGCAGTTAAC

ACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGA

CGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACC

TTACCAGGACTTGACATCCTACTAACGAAGCAGAGATGCATAAGGTGCCCTTCGGGG

AAAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTA

AGTCCCGCAACGAGCGCAACCCTTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGA

GACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTT

ATGTCCTGGGCCACACACGTACTACAATGGCGGTCAACAGAGGGAAGCAAAGCCGCG

AGGTGGAGCAAATCCCTAAAAGCCGTCCCAGTTCGGATTGCAGGCTGAAACTCGCCT

GTATGAAGTCGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCC

CGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGT

AGCCTAACAGCAATGGGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCG

TAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 64)

GCF_000765235

Oscillibacter sp ER4
TATTGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCTTAACACATGCA

AGTCGAACGAGAATCTACTGAAAGAGTTTTCGGACAATGGATGTAGAGGAAAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTTGAAGAGGGGGACAACAGTTGGAA

ACGACTGCTAATACCGCATGATGCATAGGGGTCGCATGATCTTTATGCCAAAGATTTA

TCGCTTCAAGATGGCCTCGCGTCTGATTAGCTAGTTGGCGGGGTAACGGCCCACCAAG

GCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGATACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTGA

CCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTAAGAGG

GAAGAGCAGAAGACGGTACCTCTAGAATAAGCCACGGCTAACTACGTGCCAGCAGCC

GCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGTGCA

GCCGGGTCTGCAAGTCAGATGTGAAATCCATGGGCTCAACCCATGAACTGCATTTGA

AACTGTAGATCTTGAGTGTCGGAGGGGCAATCGGAATTCCTAGTGTAGCGGTGAAAT

GCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACGATAACTGAC

GGTGAGGCGCGAAAGTGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACACT

GTAAACGATGAATACTAGGTGTGCGGGGACTGACCCCCTGCGTGCCGCAGTAAACAC

AATAAGTATTCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGACG

GGGGCCCGCACAAGCGGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTT

ACCAGGGTTTGACATCCTGCTAACGAAGTAGAGATACATTAGGTGCCCTTCGGGGAA

AGCAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAA

GTCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAG

ACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTA

TATCCTGGGCTACACACGTAATACAATGGCGGTCAACAGAGGGAAGCAAAGCCGCGA

GGCAGAGCAAACCCCCAAAAGCCGTCCCAGTTCGGATTGTAGGCTGCAACTCGCCTG

CATGAAGTCGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCC

GGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTA

GCCTAACCTGAAAAGGAGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTC

GTAACAAGGTAGCCGTTCGAGAACGAGCGGCTGGATCACCTCCTTT (SEQ ID NO: 65)

GCF_000820765

Candidatus

ATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCTTAACACATGCAA

Soleaferrea

GTCGAACGGGGTTGTTTCTGACACTCAGTGGGTAATCGGTAGATTGCTGATTGAGTGT

massiliensis

TGGGAATAACCTAGTGGCGGACGGGTGAGTAACACGTGAGCAACCTACCTTTCAGAG

GGGGATAACGTTTGGAAACGAACGCTAATACCGCATGATATAATTGGATGGCATCAT

CTGATTATCAAAGGAGCAATCCGCTGAAAGATGGGCTCGCGGCCGATTAGGTAGTTG

GAGTGGTAACGGCACACCAAGCCGACGATCGGTAGCCGGACTGAGAGGTTGAACGG

CCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATAT

TGCACAATGGGCGAAAGCCTGATGCAGCGACGCCGCGTGAGGGAAGACGGTTTTCGG

ATTGTAAACCTCTGTCTTATGTGACGATAATGACGGTAGCATAGGAGGAAGCCACGG

CTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGAATTA

CTGGGTGTAAAGGGAGCGTAGGCGGGAATGCAAGTTGAATGTTAAATCTACCGGCTC

AACCGGTAGCTGCGTTCAAAACTGTATTTCTTGAGTGAAGTAGAGGCAGGCGGAATT

CCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGC

CTGCTGGGCTTTTACTGACGCTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGA

TACCCTGGTAGTCCACGCTGTAAACGATGATTACTAGGTGTGGGGGGTCTGACCCCTT

CCGTGCCGGAGTTAACACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGA

AACTCAAAGGAATTGACGGGGACCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGA

AGCAACGCGAAGAACCTTACCAGGTCTTGACATCCAACTAACGAGGCAGAGATGCGT

TAGGTGCCCTTCGGGGAAAGTTGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTC

GTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTACTATTAGTTGCTACGCA

AGAGCACTCTAATGGGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCA

AATCATCATGCCCCTTATGACCTGGGCCACACACGTACTACAATGGTGTTCAACAGAG

GGAAGCAAAACTGTGAAGTGGAGCAAACCCCTAAAAGACATCCCAGTTCGGATCGTA

GGCTGCAACCCGCCTACGTGAAGTTGGAATTGCTAGTAATCGCGGATCAGCATGCCG

CGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGAGAGTCGGTAA

CACCCGAAGTCAGTAGCCTAACCGCAAGGAGGGCGCTGCCGAAGGTGGGATTGATGA

TTAGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCT

TT (SEQ ID NO: 66)

GCF_000953215

Clostridium cellulosi
TTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

GTCGAGCGGAGATAGTACTTCGGTTCTATCTTAGCGGCGGACGGGTGAGTAACGCGT

GAGCAACCTGCCCTTGAGCGGGGGATAGCGTCTGGAAACGGACGGTAATACCGCATA

ATGTACGTTGGAGGCATCTCCGATGTACCAAAGGAGAAATCCACTCAAGGATGGGCT

CGCGTCCGATTAGGTAGTTGGTGAGGTAATGGCCCACCAAGCCTGCGATCGGTAGCC

GGACTGAGAGGTTGTACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGG

AGGCAGCAGTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCGACGCCGCGT

GAGGGAAGAAGGTCTTCGGATTGTAAACCTCTGTCTTTCGGGACGAAGGAAGTGACG

GTACCGAAAGAGGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGG

TGGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGTGCGTAGGCGGGTTGTCAAGT

TGGATGTGAAATCTCTGGGCTTAACTCAGAGGTTGCATTCAAAACTGGCGATCTTGAG

TGAGGTAGAGGCAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGATATCGGGAG

GAACACCAGTGGCGAAGGCGGCCTGCTGGGCCTTAACTGACGCTGAGGCACGAAAGC

ATGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCATGCTGTAAACGATGATTGCT

AGGTGTGGGTGGACTGACCCCATCCGTGCCGGAGTTAACACAATAAGCAATCCACCT

GGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGC

AGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACAT

CCACCGAATCCGGAAGAGATTCTGGAGTGCCCTTCGGGGAGCGGTGAGACAGGTGGT

GCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCA

ACCCTTGTTAATAGTTGCTACGCAAGAGCACTCTATTAAGACTGCCGTTGATAAAACG

GAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACG

TACTACAATGGCCGCCAACAAAGGGAAGCAATACCGCGAGGTGGAGCGAATCCCCA

AAAGCGGTCCCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATGAAGACGGAATTGC

TAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGC

CCGTCACACCATGAGAGCCGGAAACACCCGAAGTCGTTTGCGTAACCGAAAGGAGCG

CGGCGCCGAAGGTGGGATCGGTGATTGGGGTGAAGTCGTAACAAGGTAGCCGTATCG

GAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 67)

GCF_001305095

Clostridia bacterium
TCTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

UCS 1 2F7
GTCGAACGAGCCGAGGGGAGCTTGCTCCCCAGAGCTAGTGGCGGACGGGTGAGTAAC

ACGTGAGCAACCTGCCTTTCAGAGGGGGATAACGTTTGGAAACGAACGCTAATACCG

CATAACATACCGGGACCGCATGATTCTGGTATCAAAGGAGCAATCCGCTGAAAGATG

GGCTCGCGTCCGATTAGCTAGTTGGCGGGGTAACGGCCCACCAAGGCGACGATCGGT

AGCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTA

CGGGAGGCAGCAGTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCGACGC

CGCGTGAGGGAAGACGGTCTTCGGATTGTAAACCTCTGTCTTTGGGGACGATAATGA

CGGTACCCAAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTA

GGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGGTCTCAA

GTCGAATGTTAAATCTACCGGCTCAACTGGTAGCTGCGTTCGAAACTGGGGCTCTTGA

GTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGA

GGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTTACTGACGCTGAGGCTCGAAAG

CGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTAC

TAGGTGTGGGGGACTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAATCCACCT

GGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGC

AGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATC

GAGTGACGGCTCTAGAGATAGAGCTTTCCTTCGGGACACAAAGACAGGTGGTGCATG

GTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCT

TATTATTAGTTGCTACATTCAGTTGAGCACTCTAATGAGACTGCCGTTGACAAAACGG

AGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGT

AATACAATGGCGATCAACAGAGGGAAGCAAGACCGCGAGGTGGAGCAAACCCCTAA

AAGTCGTCTCAGTTCGGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATTGCTA

GTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCC

GTCACACCATGGGAGTCGGTAACACCCGAAGTCAGTAGCCTAACCGCAAAGAGGGCG

CTGCCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGA

AGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 68)

GCF_001305115

Clostridia bacterium
TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

UC5 1 1E11
AGTCGAACGGAGTTAAGAGAGCTTGCTCTTTTAACTTAGTGGCGGACGGGTGAGTAA

CGCGTGAGTAACCTGCCTTTCAGAGGGGAATAACATTCTGAAAAGAATGCTAATACC

GCATGAGATCGTAGTATCGCATGGTACAGCGACCAAAGGAGCAATCCGCTGAAAGAT

GGACTCGCGTCCGATTAGCTAGTTGGTGAGATAAAGGCCCACCAAGGCGACGATCGG

TAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCT

ACGGGAGGCAGCAGTGGGGGATATTGCACAATGGGGGAAACCCTGATGCAGCAACG

CCGCGTGAAGGAAGAAGGTCTTCGGATTGTAAACTTCTGTCCTCAGGGAAGATAATG

ACGGTACCTGAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGT

AGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGATCTGCA

AGTCAGTAGTGAAATCCCAGGGCTTAACCCTGGAACTGCTATTGAAACTGTGGGTCTT

GAGTGAGGTAGAGGCAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGAGATCG

GGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCCTTAACTGACGCTGAGGCACGA

AAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGAT

TACTAGGTGTGGGTGGTCTGACCCCATCCGTGCCGGAGTTAACACAATAAGTAATCCA

CCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACA

AGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGA

CATCCTGCTAACGAGGTAGAGATACGTTAGGTGCCCTTCGGGGAAAGCAGAGACAGG

TGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAG

CGCAACCCCTGCTATTAGTTGCTACGCAAGAGCACTCTAATAGGACTGCCGTTGACAA

AACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACA

CACGTACTACAATGGCCGTCAACAGAGAGAAGCAAAGCCGCGAGGTGGAGCAAAAC

TCTAAAAACGGTCCCAGTTCGGATCGTAGGCTGCAACCCGCCTACGTGAAGTTGGAA

TTGCTAGTAATCGCGGATCATCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACA

CCGCCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCAGTAGTCTAACCGCAAGG

GGGACGCTGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCGT

ATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 69)

GCF_001305135

Clostridia bacterium
TTTAGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCA

UC5 1 1D1
AGTCGAACGGGGTTATTTTGGAAATCTCTTCGGAGATGGAATTCTTAACCTAGTGGCG

GACGGGTGAGTAACGCGTGAGCAATCTGCCTTTAGGAGGGGGATAACAGTCGGAAAC

GGCTGCTAATACCGCATAATACGTTTGGGAGGCATCTCTTGAACGTCAAAGATTTTAT

CGCCTTTAGATGAGCTCGCGTCTGATTAGCTGGTTGGCGGGGTAACGGCCCACCAAG

GCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCGCAATGGGGGAAACCCTGA

CGCAGCAACGCCGCGTGATTGAAGAAGGCCTCGGGTTGTAAAGATCTTTAATCAGGG

ACGAAAAATGACGGTACCTGAAGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGC

GGTAATACGTAGGGAGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGCGCAGG

CGGGCCGGCAAGTTGGGAGTGAAATCCCGGGGCTTAACCCCGGAACTGCTTTCAAAA

CTGCTGGTCTTGAGTGATGGAGAGGCAGGCGGAATTCCGTGTGTAGCGGTGAAATGC

GTAGATATACGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGACATTAACTGACGC

TGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGT

AAACGATGGATACTAGGTGTGGGAGGTATTGACCCCTTCCGTGCCGCAGTTAACACA

ATAAGTATCCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGG

GGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTA

CCAGGTCTTGACATCCCGATGACCGGCGTAGAGATACGCCCTCTCTTCGGAGCATCGG

TGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCG

CAACGAGCGCAACCCTTACGGTTAGTTGATACGCAAGATCACTCTAGCCGGACTGCC

GTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCT

GGGCTACACACGTACTACAATGGCAGTCATACAGAGGGAAGCAATACCGCGAGGTGG

AGCAAATCCCTAAAAGCTGTCCCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATGA

AGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCC

TTGTACACACCGCCCGTCACACCATGAGAGCCGTCAATACCCGAAGTCCGTAGCCTA

ACCGCAAGGGGGGCGCGGCCGAAGGTAGGGGTGGTAATTAGGGTGAAGTCGTAACA

AGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 70)

GCF_001486665

Fournierella

TATGAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCA

massiliensis

AGTCGAACGGAGCTTGCTTGTCAGATCCTTTCGGGGTGACGACTTGTAAGCTTAGTGG

CGAACGGGTGAGTAACACGTGAGTAACCTGCCCCAGAGTGGGGGACAACAGTTGGA

AACGACTGCTAATACCGCATAAGCCCACGGAACCGCATGGTTCAGAGGGAAAAGGA

GCAATTCGCTTTGGGATGGACTCGCGTCCGATTAGCTAGATGGTGAGGTAACGGCCC

ACCATGGCGACGATCGGTAGCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAG

ACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAA

ACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGCCTTCGGGTTGTAAACTCCTGT

CGTAAGGGACGATAGTGACGGTACCTTACAAGAAAGCCACGGCTAACTACGTGCCAG

CAGCCGCGGTAAAACGTAGGTGGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGA

GCGCAGGCGGGTCTGCAAGTTGGAAGTGAAACCCATGGGCTCAACCCATGAACTGCT

TTCAAAACTGCGGATCTTGAGTGGTGTAGAGGTAGGCGGAATTCCCGGTGTAGCGGT

GGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACTA

ACTGACGCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTC

CATGCCGTAAACGATGATTACTAGGTGTGGGAGGATTGACCCCTTCCGTGCCGCAGTT

AACACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAAT

TGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGA

ACCTTACCAGGTCTTGACATCCCGTGCATAGCATAGAGATATGTGAAGTCCTTCGGGA

CACGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAG

TCCCGCAACGAGCGCAACCCTTATCGTTAGTTACTACGCAAGAGGACTCTAGCGAGA

CTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTAT

GACCTGGGCTACACACGTACTACAATGGCAATTAACAAAGAGAAGCAAAGCCGCGA

GGTGGAGCAAACCTCATAAAAATTGTCTCAGTTCAGATTGCAGGCTGCAACTCGCCTG

CATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCC

GGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCCGTA

GCCTAACCGCAAGGAGGGCGCGGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGT

AACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 71)

GCF_001695555

Clostridium sp
TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

W14A
AGTCGAACGGAAACAGATTGAAGCTTGCTTTGAACTGTTTTAGTGGCGGACGGGTGA

GTAACGCGTGAGGAACCTGCCTTTCAGAGGGGGATAACGTCTGGAAACGGACGCTAA

TACCGCATGACATTTTGTTGCCGCATGGTGATAAAATCAAAGGAGCAATCCGCTGAG

AGATGGACTCGCGTCCGATTAGCCGGTTGGCGGGGTAACGGCCCACCAAAGCAACGA

TCGGTAGCCGGGCTGAGAGGCTGAACGGCCACATTGGGACTGAGACACGGCCCAGAC

TCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCA

ACGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAAACCTCTGTCCTCAGGGACGATA

ATGACGGTACCTGAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATA

CGTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGCACT

GCAAGTCAGGTGTGAAAACCATGGGCTTAACTTATGGATTGCACTTGAAACTGTGGTG

CTTGAGTGAAGTAGAGGCAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGAGAT

CGGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACGCTGAGGCAC

GAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATG

ATTACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAATC

CACCTGGGAAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCAC

AAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTG

ACATCCAACTAACGAAGCAGAGATGCATCAGGTGCCCTTCGGGGAAAGTTGAGACAG

GTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGA

GCGCAACCCTTGTGATTAGTTGCTACGCTAAGAGCACTCTAATCAGACTGCCGTTGAC

AAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTA

CACACGTACTACAATGGCCGTTAACAACGGGAAGCGAAGCCGCGAGGCGGAGCAAA

ACCCCAAAAACGGTCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAGCTGG

AATTGCTAGTAATCGCGGATCATCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACA

CACCGCCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCGGTAGCCTAACCGCAA

GGAAGGCGCCGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAAGGTAGC

CGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 72)

GCF_002119605

Ruminococcaceae

TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

bacterium CPB6
AGTCGAACGAAACTTTTTGCTTCGGTAGAAAGTTTAGTGGCGGACGGGTGAGTAACG

CGTGAGGAACCTGCCTTTCAGAGGGGGATAATGTCTGGAAACGGACACTAATACCGC

ATGACATTTTCTGTTCACATGGACAGAAAATCAAAGGAGCAATCTGCTGAAAGATGG

ACTCGCGTCCGATTAGCTAGATGGTGAGATAATAGCCCACCATGGCGACGATCGGTA

GCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTAC

GGGAGGCAGCAGTGGGGGATATTGCACAATGGAGGAAACTCTGATGCAGCAACGCC

GCGTGAAGGAAGACGGTCTTCGGATTGTAAACTTTTGTACCTAGGGACGATAATGAC

GGTACCTAGGCAGCAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAG

GGAGCGAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGCCAAGCAAG

TCAGCTGTGAAAACTATGGGCTTAACCCATAGCCTGCAATTGAAACTGTTTGGCTTGA

GTGAAGTAGAGGTAGGTGGAATTCCCGGTGTAGCGGTGAAATGCGTAGAGATCGGGA

GGAACACCAGTGGCGAAGGCGACCTACTGGGCTTTAACTGACGCTGAAGCACGAAAG

CATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCTGTAAACGATGATTAC

TAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAATCCACCT

GGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGC

AGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACAT

CCAACTAACGAAGCAGAGATGCATTAGGTGCCCTTCGGGGAAAGTTGAGACAGGTGG

TGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGC

AACCCTTACTGTTAGTTGCTACGCAAGAGCACTCTAGCAGGACTGCCGTTGACAAAAC

GGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACAC

GTACTACAATGGCCGTTAACAGAGAGAAGCGATACCGCGAGGTGGAGCGAACCTCAA

AAAGCGGTCTCAGTTCGGATTGCAGGCTGAAACCCGCCTGCATGAAGTTGGAATTGC

TAGTAATCGCGGATCATAATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGC

CCGTCACACCATGGGAGCCGGTAATACCCGAAGTCAGTAGTCTAACCGCAAGGAGGA

CGCTGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCA

GAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 73)

GCF_002159175

Flavonifractor sp
TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

An92
GTCGAACGGAGTGCTCATGACGGAGTTTTCGGACAACGGATTGAGTTACTTAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTTGGAGTGGGGAATAACAGTTGGAA

ACAGCTGCTAATACCGCATAATGCAGTTGGGTCGCATGGCCCTGACTGCCAAAGATTT

ATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTGGTTGGCGGGGTAACGGCCCACCAA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTG

ACCCAGCAACGCCGCGTGAAGGATGAAGGCTTTCGGGTTGTAAACTTCTTTTGTCAGG

GACGAAACAAATGACGGTACCTGACGAATAAGCCACGGCTAACTACGTGCCAGCAGC

CGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTGT

AGGCGGGATTGCAAGTCAGATGTGAAAACCAGGGGCTCAACCTCTGGCCTGCATTTG

AAACTGTAGTTCTTGAGTGCTGGAGAGGCAATCGGAATTCCGTGTGTAGCGGTGAAA

TGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACAGTAACTGA

CGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGC

CGTAAACGATGGATACTAGGTGTGGGGGGACTGACCCCCTCCGTGCCGCAGCTAACG

CAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGAC

GGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCT

TACCAGGGCTTGACATCCTACTAACGAAGCAGAGATGCATAAGGTGCCCTTCGGGGA

AAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAA

GTCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAG

ACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTA

TGTCCTGGGCCACACACGTACTACAATGGTGGTTAACAGAGGGAGGCAAAACCGCGA

GGTGGAGCAAATCCCTAAAAGCCATCCCAGTTCGGATTGCAGGCTGCAACCCGCCTG

TATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCC

GGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTA

GCCTAACCGCAAGGAGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCGT

AACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 74)

GCF_002159225

Flavonifractor sp
TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

An91
GTCGAACGGAGTGCTCATGACGGAGGATTCGTCCAACGGATTGAGTTACTTAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTCGGAGTGGGGAATAACAGCCCGAA

AGGGTTGCTAATACCGCATGATGCAGTTGGGCCGCATGGCTCTGACTGCCAAAGATTT

ATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTGGTTGGCGGGGTAACGGCCCACCAA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTG

ACCCAGCAACGCCGCGTGAAGGATGAAGGCTTTCGGGTTGTAAACTTCTTTTATTCGG

GACGAAGAAAATGACGGTACCGAATGAATAAGCCACGGCTAACTACGTGCCAGCAG

CCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTG

TAGGCGGGACTGCAAGTCAGATGTGAAAACTATGGGCTCAACCCATAGCCTGCATTT

GAAACTGTAGTTCTTGAGTGCTGGAGAGGCAATCGGAATTCCGTGTGTAGCGGTGAA

ATGCATAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACAGTAACTG

ACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACG

CCGTAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGCAGTTAAC

ACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGA

CGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACC

TTACCAGGGCTTGACATCCC (SEQ ID NO: 75)

GCF_002159455

Flavonifractor sp
TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

An306
GTCGAACGGAGTGCTCATGACAGAGGATTCGTCCAATGGATTGAGTTACTTAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTCGGAGTGGGGAATAACAGACCGAA

AGGCCTGCTAATACCGCATGATACAGTTGGGTCGCATGGCTCTGACTGTCAAAGATTT

ATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTAGTTGGCGGGGTAACGGCCCACCAA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTCTCGGG

GACGAAACAAATGACGGTACCTGAGGAATAAGCCACGGCTAACTACGTGCCAGCAGC

CGCGGTAATACGTAGGTGGCGAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTGT

AGGCGGGATTGCAAGTCAGACGTGAAAACTATGGGCTCAACCCATAGCCTGCGTTTG

AAACTGTAGTTCTTGAGTGCTGGAGAGGCAATCGGAATTCCGTGTGTAGCGGTGAAA

TGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACAGTAACTGA

CGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGC

CGTAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGCAGTTAACA

CAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGAC

GGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCT

TACCAGGGCTTGACATCCCACTAACGAAGCAGAGATGCATTAGGTGCCCTTCGGGGA

AAGTGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAA

GTCCCGCAACGAGCGCAACCCTTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAG

ACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTA

TGTCCTGGGCCACACACGTACTACAATGGTGGTTAACAGAGGGAAGCAATACCGCGA

GGTGGAGCAAATCCCTAAAAGCCATCCCAGTTCGGATTGCAGGCTGAAACCCGCCTG

TATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCC

GGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTA

GCCTAACAGCAATGGGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCGT

AACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 76)

GCF_002160015

Anaerofilum sp
TATAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCA

An201
AGTCGAACGGAGCTATTTCGATAGATCCCTTCGGGGTGACATTGGCTTAGCTTAGTGG

CGAACGGGTGAGTAACACGTGAGGAACCTGCCCTTCAGAGGGGGACAACAGTTGGA

AACGACTGCTAATACCGCATAAGACCACAGAGCCGCATGGCTCAGGGGTCAAAGGAG

AAATCCGCTGAAGGATGGCCTCGCGTCCGATTAGGTAGTTGGCGGGGTAACGGCCCA

CCAAGCCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGA

CACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAA

CCCTGATGCAGCGACGCCGCGTGAGGGAAGAAGATTTTCGGATTGTAAACCTCTGTCT

TCGGGGACGATAATGACGGTACCCGAGGAGGAAGCCACGGCTAACTACGTGCCAGCA

GCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGC

GCAGGCGGGTTTGCAAGTTGGATGTTTAATCGAGGGGCTCAACCCCTTTCCGCATTCA

AAACTGCAGATCTTGAGTGGTGCAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAA

TGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACTAACTGA

CGCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGC

CGTAAACGATGATTACTAGGTGTGGGGGGATTGACCCCCTCCGTGCCGCAGTTAACA

CAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGAC

GGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCT

TACCAGGTCTTGACATCCCGTGCATAGCATAGAGATATGTGAAGTCCTTCGGGACACG

GAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCC

GCAACGAGCGCAACCCTTACTGATAGTTACTACGCAAGAGGACTCTATCGGGACTGC

CGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTATATGACC

TGGGCTACACACGTACTACAATGGCTATGAACAAAGAGAAGCGAAGCCGCGAGGCA

GAGCAAACCTCATAAAAATAGTCTCAGTTCGGACTGCAGGCTGCAACTCGCCTGCAC

GAAGCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGG

CCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTC

TAACCGCAAGGAGGACGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAAC

AAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 77)

GCF_002160025

Anaeromassilibacillus

TCTTGTTGCTTAGTGGCGGACGGGTGAGTAACACGTGAGTAACCTGCCTCTCAGAGGG

sp An200
GGATAACGTCTTGAAAAGGACGCTAATACCGCATGATATCTCTTGACCGCATGGTCG

GGAGATCAAAGGAGCAATCCGCTGAGAGATGGACTCGCGTCCGATTAGCCAGTTGGC

GGGGTAACGGCCCACCAAAGCAACGATCGGTAGCCGGACTGAGAGGTTGAACGGCC

ACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTG

CACAATGGGGGAAACCCTGATGCAGCAACGCCGCGTGAAGGATGAAGGTCTTCGGAT

TGTAAACTTTTGTCCTATGGGAAGAAGAAAGTGACGGTACCATAGGAGGAAGCTCCG

GCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGAGCAAGCGTTGTCCGGATTT

ACTGGGTGTAAAGGGTGCGTAGGCGGAAGAGCAAGTCAGTAGTGAAATCTGGGGGCT

TAACCCCCAAACTGCTATTGAAACTGTTTTTCTTGAGTGGAGTAGAGGTAGGCGGAAT

TCCCGGTGTAGCGGTGAAATGCGTAGAGATCGGGAGGAACACCAGTGGCGAAGGCG

GCCTACTGGGCTCTAACTGACGCTGAGGCACGAAAGTGTGGGTAGCAAACAGGATTA

GATACCCTGGTAGTCCACACCGTAAACGATGATTACTAGGTGTGGGGGGTCTGACCC

CCTCCGTGCCGGAGTTAACACAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGT

TGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATT

CGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCAA (SEQ ID NO: 78)

GCF_002160275

Pseudoflavonifractor

AAGTGGCGGACGGGTGAGTAACGCGTGAGGAACCTGCCTCGGAGTGGGGAATAACA

sp An187
GTTGGAAACAGCTGCTAATACCGCATAATGCAACGGAATCGCATGACTCTGTTGCCA

AAGATTTATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTGGTTGGCGGGGTAACGGC

CCACCAAGGCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTG

AGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCG

CAAGCCTGACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCT

TTTGTCAGGGACGAACAAATGACGGTACCTGACGAATAAGCCACGGCTAACTACGTG

CCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTATTGGGTGTAAA

GGGCGTGTAGGCGGGACTGCAAGTCAGATGTGAAAACCACGGGCTCAACCTGTGGCC

TGCATTTGAAACTGTAGTTCTTGAGTGTCGGAGAGGCAATCGGAATTCCGTGTGTAGC

GGTGAAATGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACG

ATAACTGACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTA

GTCCACGCCGTAAACGATGGATACTAGGTGTGGGGGGACTGACCCCCTCCGTGCCGC

AGTTAACACAGTAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAG

GAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCG

AAGAACCTTACCAGGACTTGACATCCTACTAACGAAGCAGAGATGCATTAGGTGCCC

TTCGGGGAAAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATG

TTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACT

CTAGCGAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCAT

GCCCCTTATGTCCTGGGCCACACACGTACTACAATGGCGGTTAACAAAGAGAGGCAA

TACCGCGAGGTGGAGCAAATCTCAAAAAGCCGTCCCAGTTCGGATTGCAGGCTGCAA

CCCGCCTGCATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAAT

ACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGA

AGTCCGTAGCCTAACCGCAAGGGGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGT

GAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID

NO: 79)

GCF_002160305

Pseudoflavonifractor

TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

sp An184
GTCGAACGGAGAGCGTATGACAGAGGATTCGTCCAATGGATTGCGTTTCTTAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTCGGAGTGGGGAATAACACAACGAA

AGCTGTGCTAATACCGCATGATGCAGCTGGGTCGCATGACTCTGGCTGCCAAAGATTT

ATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTGGTTGGCGGGGTAACGGCCCACCAA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCCCTCGGGTTGTAAACTTCTTTTGTCAG

GGACGAAGCAAGTGACGGTACCTGACGAATAAGCCACGGCTAACTACGTGCCAGCAG

CCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTG

TAGGCGGGATTGCAAGTCAGATGTGAAAACCACGGGCTCAACCTGTGGCCTGCATTT

GAAACTGCAGTTCTTGAGTACTGGAGAGGCAGACGGAATTCCTAGTGTAGCGGTGAA

ATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGTCTGCTGGACAGCAACTG

ACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACG

CTGTAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGCAGTTAAC

ACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGA

CGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACC

TTACCAGGGCTTGACATCCCGACGACCGGTGTAGAGATACACTTTTCTCTTCGGAGAC

GTCGGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAG

TCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAGA

CTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTAT

GTCCTGGGCCACACACGTACTACAATGGTGGTCAACAGAGGGAGGCAAAACCGCGAG

GTGGAGCAAACCCCTAAAAGCCATCCCAGTTCGGATTGCAGGCTGCAACCCGCCTGC

ATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCG

GGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTAG

CCTAACCGCAAGGGGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCGTA

ACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 80)

GCF_002160515

Anaeromassilibacillus

TTTAGTGGCGGACGGGTGAGTAACGCGTGAGTAACCTGCCTTCAAGAGGGGAATAAC

sp An172
GTTCTGAAAAGAACGCTAATACCGCATAACATACGGATGTCGCATGGCAACCGTATC

AAAGATTTTATCGCTTGAAGATGGACTCGCGTCCGATTAGCCAGTTGGCGGGGTAAC

GGCCCACCAAAGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGA

CTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCGCAATGGG

GGCAACCCTGACGCAGCAACGCCGCGTGAACGATGAAGGTCTTCGGATTGTAAAGTT

CTTTTATTAAGGACGAAGAAGTGACGGTACTTAATGAATAAGCTCCGGCTAACTACGT

GCCAGCAGCCGCGGTAATACGTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAA

AGGGTGCGTAGGCGGCAGAGCAAGTCAGATGTGAAATCCGTGGGCTTAACCCACGAA

CTGCATTTGAAACTGTTTTGCTTGAGTGAAGTAGAGGCAGGCGGAATTCCCTGTGTAG

CGGTGAAATGCGTAGAGATAGGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGC

TTTAACTGACGCTGAGGCACGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGT

AGTCCACGCCGTAAACGATGATTACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGC

AGTTAACACAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAG

GAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCG

AAGAACCTTACCAGGTCTTGACATCCAACTAACGAGGTAGAGATACATTAGGTGCCC

TTCGGGGAAAGTTGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGT

TGGGTTAAGTCCCGCAACGAGCGCAACCCTTGCTATTAGTTGCTACGCAAGAGCACTC

TAATAGGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATG

CCCCTTATGACCTGGGCTACACACGTACTACAATGGCCATCAACAGAGGGAAGCAAA

GCAGCGATGCAGAGCAAACCCCTAAAAATGGTCCCAGTTCAGATTGCAGGCTGCAAC

TCGCCTGTATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATA

CGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGGGAGCCGGTAATACCCGAA

GTCAGTAGTCTAACCGCAAGGAGGACGCTGCCGAAGGTAGGATTGGCGACTGGGGTG

AAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID

NO: 81)

GCF_002160955

Gemmiger sp
TAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAAG

An120
TCGAACGGAGTTATTTTGGCTGAAGTTTTCGGATGGACGCCGGGATAACTTAGTGGCG

AACGGGTGAGTAACACGTGAGGAACCTGCCCTTGAGTGGGGGACAACAGTTGGAAAC

GACTGCTAATACCGCATAAGCCCACAGAGCCGCATGGCTCAGGGGGAAAAGGAGCA

ATTCGCTTAAGGATGGACTCGCGTCCAATTAGGTAGATGGTGAGGTAACGGCCCACC

ATGCCGACGATTGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACA

CGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCC

TGATGCAGCGACGCCGCGTGAAGGAAGAAGGCCTTCGGGTTGTAAACTTCTGTCGTA

AGGGACGATAATGACGGTACCTTACAAGAAAGCCACGGCTAACTACGTGCCAGCAGC

CGCGGTAAAACGTAGGTGGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGC

AGGCGGGGAGGCAAGTTGGAAGTGAAAAGCGTGGGCTCAACCCACGACCTGCTTTCA

AAACTGTCTCTCTTGAGTAGTGCAGAGGTAAGCGGAATTCCCGGTGTAGCGGTGGAA

TGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGGCACCAACTGA

CGCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGC

CGTAAACGATGATTACTAGGTGTGGGGAGATTGACCCTCTCCGTGCCGCAGTTAACAC

AATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACG

GGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTT

ACCAGGTCTTGACATCCGATGCATAGTGCAGAGATGCATGAAGTCCTTCGGGACATC

GAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCC

GCAACGAGCGCAACCCTTATCGTCAGTTACTACGCAAGAGGACTCTGGCGAGACTGC

CGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACC

TGGGCTACACACGTACTACAATGGCGATCAACAAAGAGAAGCGAAGCCGCGAGGCG

GAGCAAACCTCATAAACATCGTCCCAGTTCAGATTGCAGGCTGCAACTCGCCTGCATG

AAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGC

CTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCCGTAGCCT

AACCGCAAGGAGGGCGCGGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAAC

AAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 82)

GCF_002161175

Flavonifractor sp
TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

An100
GTCGAACGGAGTGCTCATGACAGAGGATTCGTCCAATGGAATGAGTTACTTAGTGGC

GGACGGGTGAGTAACGCGTGAGTAACCTGCCTTGGAGTGGGGAATAACACAACGAA

AGCTGTGCTAATACCGCATAATGCAGCTGAGTCGCATGGCTCTGGCTGCCAAAGATTT

ATCGCTCTGAGATGGACTCGCGTCTGATTAGCTAGTTGGCGGGGTAACGGCCCACCA

AGGCGACGATCAGTAGCCGGACTGAGAGGTTGGCCGGCCACATTGGGACTGAGACAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCT

GACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTCTCAG

GGACGAAGCAAGTGACGGTACCTGAGGAATAAGCCACGGCTAACTACGTGCCAGCA

GCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGT

GTAGGCGGGATTGCAAGTCAGATGTGAAAACCATGGGCTCAACTCATGGCCTGCATT

TGAAACTGTAGTTCTTGAGTACTGGAGAGGCAGACGGAATTCCTAGTGTAGCGGTGA

AATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGTCTGCTGGACAGCAACT

GACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCAC

GCTGTAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGCAGTTAA

CACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTG

ACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAAC

CTTACCAGGGCTTGACATCCCGGTGACCGGCTTAGAGATAGGCTTTTCCCTTCGGGGA

CACCGGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAA

GTCCCGCAACGAGCGCAACCCTTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGAG

ACTGCCGTTGACAAAACGGAGGAAGGCGGGGACGACGTCAAATCATCATGCCCCTTA

TGTCCTGGGCCACACACGTACTACAATGGTGGTTAACAGAGGGAAGCAATGCCGCGA

GGCGGAGCAAACCCCTAAAAGCCATCCCAGTTCGGATCGCAGGCTGCAACCCGCCTG

CGTGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCC

GGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGTA

GCTTAACCGCAAGGAGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCGT

AACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 83)

GCF_002161215

Flavonifractor sp
TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

An10
GTCGAACGGAGAACCCCTGATAGAGGATTCGTCCAATTGAAGGGAATTCTTAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTTGGAGTGGGGAATAACAGTCCGAA

AGGACTGCTAATACCGCATAATGCAGTTGGGCCGCATGGCTCTGACTGCCAAAGATTT

ATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTAGTAGGCGGGGTAACGGCCCACCTA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCCCTCGGGTTGTAAACTTCTTTTGACAG

GGACGAAGAAAATGACGGTACCTGTCGAATAAGCCACGGCTAACTACGTGCCAGCAG

CCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTG

TAGGCGGGCTGGCAAGTCAGATGTGAAAACCATGGGCTCAACCCATGGCCTGCATTT

GAAACTGTTGGTCTTGAGTGCTGGAGAGGCAATCGGAATTCCGTGTGTAGCGGTGAA

ATGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACAGTAACTG

ACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACG

CCGTAAACGATGGATACTAGGTGTGGGGGGACTGACCCCCTCCGTGCCGCAGCTAAC

GCAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGA

CGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACC

TTACCAGGGCTTGACATCCTGCTAACGAAGTAGAGATACATTAGGTGCCCTTCGGGG

AAAGCAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTT

AAGTCCCGCAACGAGCGCAACCCTTATTGTTAGTTGCTACGCAAGAGCACTCTAGCG

AGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCT

TATGTCCTGGGCCACACACGTACTACAATGGCGGTTAACAGAGGGAAGCAAAACCGC

GAGGTGGAGCAAATCCCTAAAAGCCGTCCCAGTTCGGATTGCAGGCTGAAACCCGCC

TGTATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCC

CGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGT

AGCCTAACCGCAAGGGGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCG

TAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 84)

GCF_900067065

Eubacteriaceae

TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

bacterium

AGTCGAACGGACGAGAAGGTGCTTGCACCTTCAAGTTAGTGGCGGACGGGTGAGTAA

CHKCI005
CGCGTGAGCAACCTGCCTCAAAGAGGGGGATAACGTCTGGAAACGGACGCTAATACC

GCATGACGTATTCGATAGGCATCTATTGAATACCAAAGGAGCAATCCGCTTTGAGAT

GGGCTCGCGTCTGATTAGCTAGTTGGTGGGGTAAAGGCCTACCAAGGCGACGATCAG

TAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCT

ACGGGAGGCAGCAGTGGGGGATATTGCACAATGGGGGAAACCCTGATGCAGCAACG

CCGCGTGAAGGAAGACGGTTTTCGGATTGTAAACTTCTGTTCTTAGTGACGATAATGA

CGGTAGCTAAGGAGAAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTA

GGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGGCGGGAGATCA

AGTCAGATGTGAAAACTATGGGCTCAACCCATAACCTGCATTTGAAACTGGTTTTCTT

GAGTGAAGTAGAGGCAGGCGGAATTCCGAGTGTAGCGGTGAAATGCGTAGATATTCG

GAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTTACTGACGCTGAGGCTCGAA

AGCATGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGATT

ACTAGGTGTGGGGTGGCTGACCCATTCCGTGCCGGAGTTAACACAATAAGTAATCCA

CCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACA

AGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGA

CATCCGACTAACGAAGTAGAGATACATTAGGTGCCCTTCGGGGAAAGTCGAGACAGG

TGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAG

CGCAACCCTTGTCATTAGTTGCTACGCAAGAGCACTCTAATGAGACTGCCGTTGACAA

AACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACA

CACGTACTACAATGGCCGTTAACAGAGGGAAGCAATACTGTGAAGTGGAGCAAACCC

CTAAAAACGGTCCCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATGAAGTCGGAAT

TGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACAC

CGCCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCGGTAGTCTAACCGCAAGGA

GGGCGCCGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCGTA

TCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 85)

GCF_900100595

Ruminococcaceae

TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

bacterium P7
AGTCGAACGGAGTTGAGGAGCTTGCTCCTTAACTTAGTGGCGGACGGGTGAGTAACG

CGTGAGTAACCTGCCTCTGAGAGGGGAATAACGTTCTGAAAAGAACGCTAATACCGC

ATGACACATATTTGCCGCATGACAGATATGTCAAAGATTTTATCGCTCAGAGATGGAC

TCGCGTCCGATTAGTTAGTTGGTGAGGTAACGGCTCACCAAGACCGCGATCGGTAGC

CGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGG

GAGGCAGCAGTGGGGGATATTGCGCAATGGGGGCAACCCTGACGCAGCAACGCCGC

GTGAAGGATGAAGGTTTTCGGATTGTAAACTTCTTTTCTCAGGGACGAAATTTGACGG

TACCTGAGGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGG

AGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGCTTTGTAAGTCA

GATGTGAAATCTATGGGCTCAACCCATAAACTGCATTTGAAACTACAGAGCTTGAGT

GAAGTAGAGGCAGGCGGAATTCCCTGTGTAGCGGTGAAATGCGTAGAGATAGGGAG

GAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACGCTGAGGCACGAAAGC

GTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGATTACT

AGGTGTGGGGGGACTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTAATCCACCT

GGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGC

AGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACAT

CCGACTAACGAAGTAGAGATACATCAGGTGCCCTTCGGGGAAAGTCGAGACAGGTGG

TGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGC

AACCCTTGCTATTAGTTGCTACGCAAGAGCACTCTAATAGGACTGCCGTTGACAAAAC

GGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACAC

GTACTACAATGGCCATCAACAGAGGGAAGCAAAACAGCGATGTGGAGCAAACCCCT

AAAAATGGTCTCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATGAAGTCGGAATTG

CTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCG

CCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCAGTAGCTTAACCT (SEQ ID

NO: 86)

GCF_900101355

Ruminococcus

TTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAA

bromii

GTCGAACGGAACTGCTTCGAAGGATTTCTTCGGAATGACATTGATTCAGTTTAGTGGC

GGACGGGTGAGTAACGCGTGAGTAACCTGCCTTCAAGAGGGGGATAACATTCTGAAA

AGAATGCTAATACCGCATGACATATGATTGTCGCATGGCAGACATATCAAAGATTTAT

CGCTTGAAGATGGACTCGCGTCCGATTAGTTAGTTGGTGAGGTAACGGCCCACCAAG

ACCGCGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCGCAATGGGGGCAACCCTGA

CGCAGCAACGCCGCGTGAAGGATGAAGGTTTTCGGATTGTAAACTTCTTTTATTAAGG

ACGAATAATGACGGTACTTAATGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGC

GGTAATACGTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGG

CGGCTAAGCAAGTCAGATGTGAAATCTATGGGCTCAACCCATAAACTGCATTTGAAA

CTGCATAGCTTGAGTGAAGTAGAGGCAGGCGGAATTCCCCGTGTAGCGGTGAAATGC

GTAGAGATGGGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACGC

TGAGGCACGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGT

AAACGATGATTACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGGAGTTAACACAA

TAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGG

GGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTAC

CAGGTCTTGACATCCAACTAACGAGATAGAGATATGTTAGGTGCCCTTCGGGGAAAG

TTGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTC

CCGCAACGAGCGCAACCCTTGCTATTAGTTGCTACGCAAGAGCACTCTAATAGGACT

GCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGA

CCTGGGCTACACACGTACTACAATGGGCGTTAACAGAGGGAAGCAAAATAGCGATAT

GGAGCAAACCCCTAAAAACGTTCTCAGTTCAGATTGCAGGCTGCAACCCGCCTGCAT

GAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGG

CCTTGTACACACCGCCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCAGTAGTTC

AACCGCAAGGAGAGCGCTGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAAC

AAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 87)

GCF_900103235

Ruminococcus sp
TCAGTGGCGGACGGGTGAGTAACACGTGAGCAATCTGCCTTTAAGAGGGGAATAACG

YE78
ACTGGAAACGGTCGGTAATACCGCATAACATATCGAAGCCGCATGACTTTGATATCA

AAGATTTATCGCTTAAAGATGAGCTCGCGTCTGATTAGCTAGTTGGTGAGGTAACGGC

CCACCAAGGCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTG

AGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGC

AAGCCTGATGCAGCGATGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAAACCTCTG

TTGACAGGGACGATAATGACGGTACCTGTTCAGAAAGCTCCGGCTAACTACGTGCCA

GCAGCCGCGGTAATACGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGG

AGTGTAGGCGGGACTGCAAGTCAGATGTGAAATGTAGGGGCTCAACCCCTGACCTGC

ATTTGAAACTGTAGTTCTTGAGTGAAGTAGAGGTAAGCGGAATTCCCAGTGTAGCGGT

GAAATGCGTAGATATTGGGAGGAACATCAGTGGCGAAGGCGGCTTACTGGGCTTTAA

CTGACGCTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCC

ACGCCGTAAACGATGATTACTAGGTGTGGGGGGATTGACCCCTTCCGTGCCGCAGTTA

ACACAATAAGTAATCCACCTGGGGAGTACGGTCGCAAGACTGAAACTCAAAGGAATT

GACGGGGGCCCGCACAAGCAGTGGAGTATGTGGATTAATTCGAAGCAACGCGAAGA

ACCTTACCAGGTCTTGACATCGTACGCATAGTGTAGAGATACATGAAGTCCTTCGGGA

CGTATAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAG

TCCCGCAACGAGCGCAACCCTTACTGTTAGTTGCTACGCAAGAGCACTCTAGCAGGA

CTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTAT

GACCTGGGCCTCACACGTACTACAATGGCTGTTAACAGAGGGAAGCGAAGCCGCGAG

GTGGAGCAAATCCCCAAAAGCAGTCTTAGTTCGGATTGTAGGCTGCAACCCGCCTAC

ATGAAGTCGGAATTGCTAGTAATCGCAGATCAGCATGCTGCGGTGAATACGTTCCCG

GGCCTTGTACACACCGCCCGTCACACCATGGGAGTTGGTAACACCCGAAGTCAGTAG

CCTAACCGCAAGGAGGGCGCTGCCGAAGGTGGGATCGATGACTGGGGTGAAGTCGTA

ACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 88)

GCF_900104495

Ruminococcaceae

ATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCTTAACACATGCAA

bacterium FB2012
GTCGAACGGAGTTATTTGAGCTTGCTTAAATAACTTAGTGGCGGACGGGTGAGTAAC

ACGTGAGCAATCTGCCTTTCAGAGGGGGATAGCAGTTGGAAACGACTGATAATACCG

CATAATATAACGAAACCGCATGACCCTGCTATCAAAGATTTATCGCTGAAAGATGAG

CTCGCGTCTGATTAGGTAGTTGGTGAGGTAACGGCTCACCAAGCCGACGATCAGTAG

CCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACG

GGAGGCAGCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAGCGATGCCGC

GTGAGGGAAGAAGGTTTTAGGATTGTAAACCTCTGTCCTATGGAAAGATAATGACGG

TACCATAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGG

AGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGTGTAGGCGGGACTGCAAGTC

AGATGTGAAAACTATGGGCTTAACCCATAGACTGCATTTGAAACTGCAGTTCTTGAGT

GAAGTAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGG

AACATCAGTGGCGAAGGCGGCTTACTGGGCTTTAACTGACGCTGAGGCTCGAAAGCG

TGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTACTA

GGTGTGGGGGGACTGACCCCTTC (SEQ ID NO: 89)

GCF_900104565

Ruminococcaceae

CTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCACGCCTAACACATGCAAG

bacterium Marseille
TCGAACGGAGCTATTTTAGCGGAAGCCTTCGGGCAGAAGCTGGCTTAGCTTAGTGGC

P2935
GGACGGGTGAGTAACACGTGAGCAACCTGCCTTTGCGAGGGGGATAACGTTTGGAAA

CGAACGCTAATACCGCATAATGTCAGAAGGTCGCATGATTTTCTGACCAAAGATTTAT

CGCGCAAAGATGGGCTCGCGTCCGATTAGATAGTTGGTGAGGTAACGGCCCACCAAG

TCTGCGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGAGGGAACTCTGA

TGCAGCGATGCCGCGTGAGGGAAGACGGTCTTCGGATTGTAAACCTCTGTCTTCAGG

GACGAACACAATGACGGTACCTGAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGC

CGCGGTAATACGTAGGGAGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGTGT

AGGCGGGTCTCCAAGTCCGTTGTCAAATCTATCGGCTCAACCGATAGCCGCGGCGGA

AACTGGAGGTCTTGAGTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAAT

GCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGAC

GCTGAGGCTCGAAAGTGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACACT

GTAAACGATGATTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGGAGTTAACAC

AATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACG

GGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTT

ACCAGGTCTTGACATCGGATGCATACCATAGAGATATGGGAAGCCCTTCGGGGCATC

CAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCC

GCAACGAGCGCAACCCTTATCCTTAGTTGCTACGCAAGAGCACTCTAAAGAGACTGC

CGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACC

TGGGCTACACACGTACTACAATGGCGATTAACAAAGGGATGCAACACGGCGACGTGA

AGCGGAACCCAAAAAATCGTCTCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATGA

AGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCC

TTGTACACACCGCCCGTCACACCATGGGAGTCGGTAACACCCGAAGTCAGTAGCCTA

ACCGCAAGGAGGGCGCTGCCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACA

AGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 90)

GCF_900110045

Hydrogenoanaero-

AGTTTAGTGGCGGACGGGTGAGTAACACGTGAGCAACCTGCCTTTCAGAGGGGAATA

bacterium

ACATTCGGAAACGAATGCTAATACCGCATAATGCAACGAGATGGCATCATCTTGCTG

saccharovorans

CCAAAGATTTATCGCTGAAAGATGGGCTCGCGCCCGATTAGCTAGTTGGTGAGGTAA

TGGCCCACCAAGGCAACGATCGGTAGCCGGACTGAGAGGTTGATCGGCCACATTGGG

ACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGG

GCGAAAGCCTGATGCAGCGACGCCGCGTGAGGGAAGACGGTTTTCGGATTGTAAACC

TCTGTCTTCAGGGACGATAATGACGGTACCTGAGGAGGAAGCACCGGCTAACTACGT

GCCAGCAGCCGCGGTAATACGTAGGGTGCAAGCGTTGTCCGGAATTACTGGGTGTAA

AGGGAGCGTAGGCGGGATTGTAAGTTGGATGTGTAATGTACCGGCTCAACCGGTAAC

TTGCATTCAAAACTGCAGTTCTTGAGTGAAGTAGAGGCAGGCGGAATTCCTAGTGTAG

CGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCT

TTTACTGACGCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTA

GTCCATGCCGTAAACGATGATTACTAGGTGTGGGTGTGCAAGCATCCGTGCCGCAGCT

AACGCAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGCTGAAACTCAAAGGAAT

TGACGGGGGCCCGCACAAGCAGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAGA

ACCTTACCAGGTCTTGACATCCCTTGCATACCATAGAGATATGGGAAGCCCTTCGGGG

CAAGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAA

GTCCCGCAACGAGCGCAACCCTTACTATTAGTTGCTACGCAAGAGCACTCTAATAGG

ACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTA

TGACCTGGGCTACACACGTAATACAATGACGATAAACAGAGGGTAGCGAAGCCGCGA

GGTGGAGCCAATCCCCAAAAGTCGTCTCAGTTCGGATTGCAGGCTGCAACTCGCCTGC

ATGAAGTCGGAATTGCTAGTAATCGCAGGTCAGCATACTGCGGTGAATACGTTCCCG

GGCCTTGTACACACCGCCCGTCACACCATGGGAGTCGGTAACACCCGAAGCCAGTAG

TCTAACCGCAAGGAGGACGCTGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTA

ACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 91)

GCF_900113995

Ruminococcaceae

CAAAGATTTATCGCTGTGAGATGGATTCGCGTCCGATTAGATAGTTGGTGAGGTAACG

bacterium D5
GCCCACCAAGTCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGAC

TGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGGC

GCAAGCCTGATGCAGCGACGCCGCGTGTGGGAAGACGGCCCTCGGGTTGTAAACCAC

TGGCTTTGGGGACGATAATGACGGTACCCAAGGAGGAAGCTCCGGCTAACTACGTGC

CAGCAGCCGCGGTAATACGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAG

GGAGCGTAGGCGGGAGTGCAAGTTGAATGTTTAATCTATGGGCTCAACCCATATCAG

CGTTCAAAACTGCATTTCTTGAGTGAAGTAGAGGTTGGCGGAATTCCTAGTGTAGCGG

TGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCCAACTGGGCTTTT

ACTGACGCTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTC

CACGCCGTAAACGATGAATACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGT

TAACACAATAAGTATTCCACCTGGGGAGTACGGCCGCAAGGCTGAAACTCAAAGGAA

TTGACGGGGGCCCGCACAAGCAGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAG

AACCTTACCAGGCCTTGACATCTCCTGAGTAGCCTAGAGATAGGTGATGCCCTTCGGG

GCAGGAAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTA

AGTCCCGCAACGAGCGCAACCCTTACGGATAGTTGCTACGCAAGAGCACTCTATCAG

GACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTT

ATGGCCTGGGCTACACACGTAATACAATGGCGTTTAACAGAGGGAAGCAAGACCGCG

AGGTGGAGCGAATCCTCAAAAGGCGTCTCAGTTCAGATTGCAGGCTGCAACCCGCCT

GCATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCT

CGGGCCTTGTACACACCGCCCGTCACACCATGGAAGTCGGTAACACCCGAAGTCAGT

AGCCTAACCGCAAGGGGGGCGCTGCCGAAGGTGGGATTGGTAACTGGGGTGAAGTCG

TAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 92)

GCF_900115635

Oscillibacter sp
TGCCAAAGATTTATCGCTGAAAGATGGCCTCGCGTCTGATTAGCTAGTTGGTGGGGTA

PC13
ACGGCCCACCAAGGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGG

GACTGAGATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATG

GACGCAAGTCTGACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAAC

TTCTTTTAAGTGGGAAGAGCAGAAGACGGTACCACTTGAATAAGCCACGGCTAACTA

CGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTG

TAAAGGGCGTGTAGCCGGGTGTGCAAGTCAGATGTGAAATCTGGAGGCTCAACCTCC

AAACTGCATTTGAAACTGTGCATCTTGAGTATCGGAGAGGTAATCGGAATTCCTTGTG

TAGCGGTGAAATGCGTAGATATAAGGAAGAACACCAGTGGCGAAGGCGGATTACTG

GACGACAACTGACGGTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCC

TGGTAGTCCACGCTGTAAACGATCAATACTAGGTGTGCGGGGACTGATCCCCTGCGTG

CCGCAGTTAACACAATAAGTATTGCACCTGGGGAGTACGATCGCAAGGTTGAAACTC

AAAGGAATTGACGGGGGCCCGCACAAGCGGTGGATTATGTGGTTTAATTCGAAGCAA

CGCGAAGAACCTTACCAGGGCTTGACATCCTACTAATGAAGCAGAGATGCATTAAGT

GCCCTTCGGGGAAAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGA

GATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAG

CACTCTAGCGAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCA

TCATGCCCCTTATGTCCTGGGCTACACACGTAATACAATGGCGGTTAACAGAGGGATG

CAAATCCGCGAGGAGGAGCGAACCCCGAAAAGCCGTCTCAGTTCGGATCGCAGGCTG

CAACCCGCCTGCGTGAAGTCGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTG

AATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACC

CGAAGTCCGTAGCCTAACCGCAAGGAGGGCGCGGCCGAAGGTGGGTTCGATAATTGG

GGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT

(SEQ ID NO: 93)

GCF_900169975

Pseudoflavonifractor

TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

sp Marseille P3106
GTCGAACGGAGAGCCAATGACGGAGTTTTCGGACAACGGATTTGGTTTCTTAGTGGC

GGACGGGTGAGTAACGCGTGAGCAACCTGCCTTGGAGTGGGGAATAACAGCTGGAA

ACAGTTGCTAATACCGCATAATGCAGCGAGGGGACATCCTCTTGCTGCCAAAGATTTA

TCGCTCTGAGATGGACTCGCGTCTGATTAGCTGGTTGGCGGGGTAACGGCCCACCAA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGATACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGAAAGCCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCCCTCGGGTTGTAAACTTCTTTTATCAG

GGACGAAACAAATGACGGTACCTGATGAATAAGCCACGGCTAACTACGTGCCAGCAG

CCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTG

TAGGCGGGTCTGCAAGTCAGGTGTGAAATTCCAGGGCTCAACCCTGGAACTGCACTT

GAAACTGTGGGTCTTGAGTGATGGAGAGGCAGGCGGAATTCCGTGTGTAGCGGTGAA

ATGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGACATTAACTG

ACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACG

CTGTAAACGATGGATACTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGCAGTTAAC

ACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGA

CGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACC

TTACCAGGGCTTGACATCCTACTAACGAAGCAGAGATGCATTAGGTGCCCTTCGGGG

AAAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTA

AGTCCCGCAACGAGCGCAACCCTTATTGCTAGTTGCTACGCAAGAGCACTCTAGCGA

GACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTT

ATGTCCTGGGCCACACACGTACTACAATGGCGGTCAACAGAGGGAAGCAATACCGCG

AGGTGGAGCGAATCCCTAAAAGCCGTCCCAGTTCGGATTGCAGGCTGAAACCCGCCT

GCATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCC

CGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGT

AGCCTAACCGCAAGGGGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCG

TAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 94)

GCF_900197595

Neglecta sp
TTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAA

Marseille P3890
GTCGAACGGAGTTAAGAGAAGCTTGCTTTTATTAACTTAGTGGCGGACGGGTGAGTA

ACGCGTGAGCAATCTGCCTTTCAGTGGGGAATAACGTTCTGAAAAGAACGCTAATAC

CGCATAATATTGTTGAGCCGCATGGTTTGATAATCAAAGGATTTATTCGCTGAAAGAT

GAGCTCGCGTCCGATTAGATAGTTGGTGAGGTAACGGCTCACCAAGTCGACGATCGG

TAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCT

ACGGGAGGCAGCAGTGAGGGATATTGGTCAATGGGGGAAACCCTGAACCAGCAACG

CCGCGTGAGGGAAGACGGTTTTCGGATTGTAAACCTCTGTCCTCTGTGAAGATAATGA

CGGTAGCAGAGGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTA

GGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGCTATGCAA

GTCAGGAGTGAAATCTATGGGCTTAACCCATAAACTGCTCTTGAAACTGTATAGCTTG

AGTGAAGTAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGAGATCGGG

AGGAACACCAGTGGCGAAGGCGGCCTACTGGGCTTTAACTGACGCTGAAGCACGAAA

GCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTA

CTAGGTGTGGGGGGTCTGACCCCCTCCGTGCCGGAGTTAACACAATAAGTAATCCAC

CTGGGGAGTACGGTCGCAAGACTGAAACTCAAAGGAATTGACGGGGGCCCGCACAA

GCAGTGGAGTATGTGGATTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGAC

ATCCCTCTGACCGCTCTAGAGATAGAGCTTCTCTTCGGAGCAGAGGTGACAGGTGGTG

CATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAA

CCCCTATGATTAGTTGCTACGCAAGAGCACTCTAATCAGACTGCCGTTGACAAAACGG

AGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCCTCACACGT

ACTACAATGGCCGTTAACAACGGGATGCAATATAGCGATATGGAGCAAAACCCCAAA

AACGGTCTCAGTTCGGATTGTAGGCTGAAACTCGCCTGCATGAAGCTGGAATTGCTAG

TAATCGCAGATCAGAATGCTGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCG

TCACACCATGGGAGCCGGTAATACCCGAAGTCAGTAGCCTAACCGTAAGGAGGGCGC

TGCCGAAGGTAGGGTTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAA

GGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 95)

GCF_900199495

Clostridium sp
TATTGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAA

SN20
GTCGAACGGAGTGCTCATGACGGAGTTTTCGGACAACGGATTGGGTTACTTAGTGGC

GGACGGGTGAGTAACGCGTGAGGAACCTGCCTCGGAGTGGGGAATAACATACCGAA

AGGTGTGCTAATACCGCATAATGCAGTTGGGTCGCATGACTCTGACTGCCAAAGATTT

ATCGCTCTGAGATGGCCTCGCGTCTGATTAGCTAGTTGGCGGGGTAACGGCCCACCAA

GGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGGCGCAAGCCTG

ACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTGTCAG

GGACGAAACAAATGACGGTACCTGACGAATAAGCCACGGCTAACTACGTGCCAGCAG

CCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGTG

TAGGCGGGACTGCAAGTCAGGTGTGAAAACCAGGGGCTCAACCTCTGGCCTGCATTT

GAAACTGTAGTTCTTGAGTGCTGGAGAGGCAATCGGAATTCCGTGTGTAGCGGTGAA

ATGCGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGATTGCTGGACAGTAACTG

ACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACG

CCGTAAACGATGGATACTAGGTGTGGGGGGACTGACCCCCTCCGTGCCGCAGTTAAC

ACAATAAGTATCCCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATTGA

CGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACC

TTACCAGGGCTTGACATCCTACTAACGAAGCAGAGATGCATTAGGTGCCCTTCGGGG

AAAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTA

AGTCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCACTCTAGCGA

GACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTT

ATGTCCTGGGCCACACACGTACTACAATGGTGGTTAACAGAGGGAAGCAATACCGCG

AGGTGGAGCAAATCCCTAAAAGCCATCCCAGTTCGGATTGCAGGCTGAAACCCGCCT

GTATGAAGTTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCC

CGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCCGAAGTCCGT

AGCCTAACCGCAAGGAGGGCGCGGCCGAAGGTGGGTTCGATAATTGGGGTGAAGTCG

TAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 96)

GCF_900199635

Anaerotruncus sp
CAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAAG

AT3
TCGAACGGAGTGTTTTCACGGAAGTTTTCGGATGGAAGTGGTTACACTTAGTGGCGGA

CGGGTGAGTAACACGTGAGCAACCTGCCTTTCAGAGGGGGATAACAGTTGGAAACGA

CTGCTAATACCGCATGATATTACCGGGTCACATGGCCTGGCAATCAAAGGAGCAATC

CGCTGAAAGATGGGCTCGCGTCCGATTAGCCAGTTGGCGGGGTAATGGCCCACCAAA

GCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGGCGAAAGCCTGA

TGCAGCGACGCCGCGTGAGGGAAGACGGTCTTCGGATTGTAAACCTCTGTCTTAGGG

GAAGAAAATGACGGTACCCTAAGAGGAAGCTCCGGCTAACTACGTGCCAGCAGCCGC

GGTAATACGTAGGGAGCGAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTAGG

CGGGATGCCAAGTAGAATGTTAAATCCATCGGCTCAACTGGTGGCAGCGTTCTAAAC

TGGCGTTCTTGAGTGAGGTAGAGGCAGGCGGAATTCCTAGTGTAGCGGTGAAATGCG

TAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCCTTAACTGACGCT

GAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTA

AACGATGAATCCTAGGTGTGGGGGGACTGACACCTTCCGTGCCGCAGTTAACACAAT

AAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGG

GCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACC

AGGTCTTGACATCGGATGCATACCATAGAGATATGGGAAGCCCTTCGGGGCATCCAG

ACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCA

ACGAGCGCAACCCTTATTATTAGTTGCTACGCAAGAGCACTCTAATGAGACTGCCGTT

GACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGG

CTACACACGTACTACAATGGCACTCAAACAGAGGGAAGCGACACCGCGAGGTGAAG

CGGATCCCAAAAAAGTGTCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAG

TCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTG

TACACACCGCCCGTCACACCATGGGAGTCGGTAACACCCGAAGCCAGTAGCCTAACC

GCAAGGAGGGCGCTGTCGAAGGTGGGATTGATGACTGGGGTGAAGTCGTAACAAGGT

AGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 97)

GCF_900291955

Anaeromassilibacillus

TTTTGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAA

sp Marseille
GTCGAACGAAGCTTTGAGGAGCTTGCTTTTTAAAGCTTAGTGGCGGACGGGTGAGTA

P3876
ACGCGTGAGCAACCTGCCTCTCAGAGGGGGATAACGTTTTGAAAAGAACGCTAATAC

CGCATAACATATCGGAACCGCATGATTCTGATATCAAAGGAGCAATCCGCTGAGAGA

TGGGCTCGCGTCCGATTAGTTAGTTGGTGAGGTAACGGCTCACCAAGACTACGATCG

GTAGCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAGACTCC

TACGGGAGGCAGCAGTGGGGGATATTGCGCAATGGGGGAAACCCTGACGCAGCAAC

GCCGCGTGAAGGAAGAAGGTCTTCGGATTGTAAACTTCTTTTGTCAGGGACGAAGAA

AGTGACGGTACCTGACGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAAT

ACGTAGGGAGCGAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTAGGCGGCCG

AGCAAGTCAGTTGTGAAAACTATGGGCTTAACCCATAACGTGCAATTGAAACTGTCC

GGCTTGAGTGAAGTAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGAAATGCGTAGAG

ATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCTTTAACTGACGCTGAGGC

ACGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGA

TGATTACTAGGTGTGGGGGGACTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTA

ATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCG

CACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTC

TTGACATCCTGAGAATCCTTAAGAGATTAGGGAGTGCCTTCGGGAACTCAGAGACAG

GTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGA

GCGCAACCCTTGCTATTAGTTGCTACGCAAGAGCACTCTAATAGGACTGCCGTTGACA

AAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTAC

ACACGTACTACAATGGCCATTAACAGAGGGAAGCAAAACCGCGAGGCAGAGCAAAC

CCCTAAAAATGGTCCCAGTTCGGATTGTAGGCTGCAACCCGCCTACATGAAGTTGGA

ATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACAC

ACCGCCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCAGTAGTCTAACAGCAAT

GAGGACGCTGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAACAAGGTAGCC

GTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 98)

STS00001

Gemmiger formicilis
TATAAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCA

AGTCGAACGGAACTTGAGAGAGCTTGCTTTTTCAAGTTTAGTGGCGAACGGGTGAGT

AACGCGTGAGTAACCTGCCCTGGAGTGGGGGACAACAGTTGGAAACGACTGCTAATA

CCGCATAAGCCCACGGCACCGCATGGTACTGAGGGAAAAGGATTTATTCGCTTCAGG

ATGGACTCGCGTCCAATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGACGATT

GGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTC

CTACGGGAGGCAGCAGTGGGGGATATTGCACAATGGGGGAAACCCTGATGCAGCGA

CGCCGCGTGGAGGAAGAAGGTTTTCGGATTGTAAACTCCTGTCGTACGGGACGATAA

TGACGGTACCGTACAAGAAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAAAAC

GTAGGTGGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGACCGG

CAAGTTGGAAGTGAAATCTATGGGCTCAACCCATAAATTGCTTTCAAAACTGCTGGCC

TTGAGTAGTGCAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATC

GGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACCAACTGACGCTGAGGCTC

GAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATG

ATTACTAGGTGTTGGAGGATTGACCCCTTCAGTGCCGCAGTTAACACAATAAGTAATC

CACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCAC

AAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTG

ACATCCGATGCATAGTGCAGAGATGCATGAAGTCCTTCGGGACATCGAGACAGGTGG

TGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGC

AACCCTTATTGCCAGTTACTACGCAAGAGGACTCTGGCGAGACTGCCGTTGACAAAA

CGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACCTGGGCTACACA

CGTACTACAATGGCGTTTAACAAAGAGAAGCAATACCGCGAGGTGGAGCAAAACTCA

AAAACAACGTCTCAGTTCAGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATT

GCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACC

GCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCCGTAGTCTAACCGCAAGGAG

GACGCGGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAGGTAGCCGTAT

CGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 99)

STS00002

Ruminococcaceae

TTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAA

unnamed sp 1
GTCGAACGGAACTTCTTTAAAGGATTTCTTCGGAATGAATTTGATTAAGTTTAGTGGC

GGACGGGTGAGTAACGCGTGAGTAACCTGCCTCTAAGAGGGGAATAACATTCTGAAA

AGAATGCTAATACCGCATAATATATATTTATCGCATGGTAGATATATCAAAGATTTAT

CGCTTAGAGATGGACTCGCGTCCGATTAGTTAGTTGGTGAGGTAACGGCTCACCAAG

ACCGCGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGG

CCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCGCAATGGGGGAAACCCTGA

CGCAGCAACGCCGCGTGAAGGATGAAGGTCTTCGGATTGTAAACTTCTTTTATTAAGG

ACGAAGAAAGTGACGGTACTTAATGAATAAGCTCCGGCTAACTACGTGCCAGCAGCC

GCGGTAATACGTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTGCGTA

GGCGGCTTTGCAAGTCAGATGTGAAATCTATGGGCTCAACCCATAGCCTGCATTTGAA

ACTGCAGAGCTTGAGTGAAGTAGAGGCAGGCGGAATTCCCCGTGTAGCGGTGAAATG

CGTAGAGATGGGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCTTTAACTGACG

CTGAGGCACGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTG

TAAACGATGATTACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGGAGTTAACACA

ATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGG

GGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTA

CCAGGTCTTGACATCCTACTAACGAGATAGAGATATGTTAGGTGCCCTTCGGGGAAA

GTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGT

CCCGCAACGAGCGCAACCCTTGCTATTAGTTGCTACGCAAGAGCACTCTAATAGGACT

GCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGA

CCTGGGCTACACACGTACTACAATGGACATTAACAGAGGGAAGCAATACAGTGATGT

GGAGCAAACCCCTAAAAATGTTCTCAGTTCAGATTGCAGGCTGCAACCCGCCTGTATG

AAGATGGAATTGCTAGTAATCGCAGATCAGCATGCTGCGGTGAATACGTTCCCGGGC

CTTGTACACACCGCCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCAGTAGTCT

AACCGCAAGGAGGACGCTGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTCGTAAC

AAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 100)

STS00003

Ruminococcaceae

GAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGG

unnamed sp 2
GGAATATTGCGCAATGGGGGAAACCCTGACGCAGCAACGCCGCGTGATTGAAGAAG

GCCTTCGGGTTGTAAAGATCTTTAATTGGGGACGAAAAATGACGGTACCCAAAGAAT

AAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGAGCAAGCGTTAT

CCGGATTTACTGGGTGTAAAGGGCGAGTAGGCGGGCTGGCAAGTTGGGAGTGAAATC

CCGGGGCTTAACCCCGGAACTGCTTTCAAAACTGCTGGTCTTGAGTGATGGAGAGGC

AGGCGGAATTCCGTGTGTAGCGGTGAAATGCGTAGATATACGGAGGAACACCAGTGG

CGAAGGCGGCCTGCTGGACATTAACTGACGCTGAGGAGCGAAAGCGTGGGGAGCAA

ACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGGATACTAGGTGTGGGAG

GTATTGACCCCTTCCGTGCCGGAGTTAACACAATAAGTATCCCACCTGGGGAGTACGG

CCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGT

GGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCCTCTGACCGCC

CTAGAGATAGGGTTTCCCTTCGGGGCAGAGGTGACAGGTGGTGCATGGTTGTCGTCA

GCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTACGGTTAGT

TGATACGCAAGATCACTCTAGCCGGACTGCCGTTGACAAAACGGAGGAAGGTGGGGA

CGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTACTACAATGGCAGT

CATACAGAGGGAAGCAAAACAGTGATGTGGAGCAAATCCCTAAAAGCTGTCCCAGTT

CAGATTGCAGGCTGCAACTCGCCTGCATGAAGTCGGAATTGCTAGTAATCGCGGATC

AGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGA

GAGCCGGTAATACCCGAAGTCCGTAGCCTAACCGCAAGGAGGGCGCGGCCGAAGGT

AGGACTGGTAATTAGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTG

GATCACCTCCTTT (SEQ ID NO: 101)

STS00004

Gemmiger formicilis
AAAAGGATTTATTCGCTTTAGGATGGACTCGCGTCCAATTAGCTAGTTGGTGAGGTAA

CGGCCCACCAAGGCGACGATTGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGG

ACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCACAATGG

GGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTTTTCGGATTGTAAACT

CCTGTCGTTAGGGACGATAATGACGGTACCTAACAAGAAAGCACCGGCTAACTACGT

GCCAGCAGCCGCGGTAAAACGTAGGGTGCAAGCGTTGTCCGGAATTACTGGGTGTAA

AGGGAGCGCAGGCGGGAAGACAAGTTGGAAGTGAAAACCATGGGCTCAACCCATGA

ATTGCTTTCAAAACTGTTTTTCTTGAGTAGTGCAGAGGTAGATGGAATTCCCGGTGTA

GCGGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGTCTACTGGGC

ACCAACTGACGCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGT

AGTCCATGCCGTAAACGATGATTACTAGGTGTTGGGGGATTGACCCCCTCAGTGCCGC

AGTTAACACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAG

GAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCG

AAGAACCTTACCAGGTCTTGACATCCGATGCATAGCACAGAGATGTGTGAAATCCTTC

GGGACATCGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGT

TAAGTCCCGCAACGAGCGCAACCCTTATTGCCAGTTACTACGTTAAGAGGACTCTGGC

GAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCT

TTATGACCTGGGCTACACACGTACTACAATGGCGTTAAACAAAGAGAAGCAAGACCG

CGAGGTGGAGCAAAACTCAAAAACAACGTCTCAGTTCAGATTGCAGGCTGCAACTCG

CCTGCATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGT

TCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTC

GATAGTCTAACCGCAAGGAGGACGTCGCCGAAGGTAAAACTGGTGATTGGGGTGAAG

TCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID

NO: 102)

STS00005

Ruminococcaceae

GCTTAGTGGCGGACTGGTGAGTAACGCGTGAGGAACCTGCCTTTCAGAGGGGGACAA

unnamed sp 3
CAGTTGGAAACGACTGCTAATACCGCATGATGCATATTGACCGCATGGTCGGTATGTC

AAAGATTTATCGCTGAAAGATGGCCTCGCGTCTGATTAGCTTGTTGGTGAGGTAACGG

CCCACCAAGGCGACGATCAGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACT

GAGATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGAC

GCAAGTCTGACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTC

TTTGACAGGGGAAGAGTAGAAGACGGTACCCTGAAAACAAGCCACGGCTAACTACGT

GCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTGTAA

AGGGCGTGTAGCCGGGAAGGCAAGTCAGATGTGAAATCTGGAGGCTCAACCTCCAAA

CTGCATTTGAAACTGTCTTTCTTGAGTATCGGAGAGGTAATCGGAATTCCTTGTGTAG

CGGTGAAATGCGTAGATATAAGGAGGAACACCAGTGGCGAAGGCGGATTACTGGAC

GACAACTGACGGTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGG

TAGTCCACGCTGTAAACGATCAATACTAGGTGTGCGGGGACTGACCCCCTGCGTGCC

GGAGTTAACACAATAAGTATTGCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAA

AGGAATTGACGGGGGCCCGCACAAGCGGTGGATTATGTGGTTTAATTCGAAGCAACG

CGAAGAACCTTACCAGGGCTTGACATCCTACTAATGAAGCAGAGATGCATTAAGTGC

CCTTCGGGGAAAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGA

TGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATTGTTAGTTGCTACGCAAGAGCA

CTCTAGCGAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATC

ATGCCCCTTATGTCCTGGGCCACACACGTAATACAATGGCGGTAAACAGAGGGATGC

AAAGCCGTGAGGTGGAGCGAACCCCTAAAAGCCGTCCCAGTTCGGATTGCAGGCTGC

AACCCGCCTGCATGAAGTCGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGA

ATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGGGAACACCC

GAAGCCCGTAGCCTAACAGCAATGAGGGCGCGGTCGAAGGTGGGTTCGATAATTGGG

GTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ

ID NO: 103)

STS00006

Ruminococcaceae

TATAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCTTAACACATGCA

unnamed sp 4
AGTCGAACGGAGCACCCCTGAATGAGGTTTCGGCCAAAGGAAGGGAATGCTTAGTGG

CGGACTGGTGAGTAACGCGTGAGGAACCTGCCTTTCAGAGGGGGACAACAGTTGGAA

ACGACTGCTAATACCGCATGACACATGAATGGGGCATCCCATTGATGTCAAAGATTT

ATCGCTGAAAGATGGCCTCGCGTCCCATTAGCTAGTAGGCGGGGTAACGGCCCACCT

AGGCGACGATGGGTAGCCGGACTGAGAGGTTGACCGGCCACATTGGGACTGAGATAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGACGCAAGTCT

GACCCAGCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAAACTTCTTTTGTCA

GGGAACAGTAGAAGAGGGTACCTGACGAATAAGCCACGGCTAACTACGTGCCAGCA

GCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGT

GCAGCCGGGCTGGCAAGTCAGGCGTGAAATCCCAGGGCTCAACCCTGGAACTGCGTT

TGAAACTGCTGGTCTTGAGTACCGGAGAGGTCATCGGAATTCCTTGTGTAGCGGTGAA

ATGCGTAGATATAAGGAAGAACACCAGTGGCGAAGGCGGATGACTGGACGGCAACT

GACGGTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCA

CGCTGTAAACGATCAATACTAGGTGTGCGGGGACTGACCCCCTGCGTGCCGCAGTTA

ACACAATAAGTATTGCACCTGGGGAGTACGATCGCAAGGTTGAAACTCAAAGGAATT

GACGGGGGCCCGCACAAGCGGTGGATTATGTGGTTTAATTCGAAGCAACGCGAAGAA

CCTTACCAGGGCTTGACATCCTACTAACGAAGTAGAGATACATTAGGTGCCCTTCGGG

GAAAGTAGAGACAGGTGGTGCATGGTTGTCGTCAGCT (SEQ ID NO: 104)

STS00007

Ruminococcaceae

TTTAGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCA

unnamed sp 5
AGTCGAACGGAGTTATTTAAATAGAACCCTTCGGGGTGACGTTTTAATAACTTAGTGG

CGGACGGGTGAGTAACGCGTGAGTAACCTGCCTTTCAGAGGGGGATAACGTCCTGAA

AAGGACGCTAATACCGCATGATATATTTGTGCCGCATGGTATGGATATCAAAGGAGC

AATCCGCTGGAAGATGGACTCGCGTCCGATTAGCTAGTTGGAGGGGTAACGGCCCAC

CAAGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGAC

ACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGGATATTGCGCAATGGGGGAAAC

CCTGACGCAGCAACGCCGCGTGAAGGAAGAAGGTTTTCGGATTGTAAACTTCTTTTCT

AAGGGACGAAGAAGTGACGGTACCTTAGGAATAAGCTCCGGCTAACTACGTGCCAGC

AGCCGCGGTAATACGTAGGGAGCAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGTG

CGTAGGCGGCAATGCAAGTCAGATGTGAAATGCACGGGCTCAACCCGTGAGCTGCAT

TTGAAACTGTGTTGCTTGAGTGAGGTAGAGGCAGGCGGAATTCCCGGTGTAGCGGTG

AAATGCGTAGAGATCGGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGGCCTTAAC

TGACGCTGATGCACGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCA

CGCTGTAAACGATGATTACTAGGTGTGGGGGGTCTGACCCCTTCCGTGCCGCAGTTAA

CACAATAAGTAATCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTG

ACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAAC

CTTACCAGGTCTTGACATCCAGCTAACGAAGTAGAGATACATTAGGTGCCCTTCGGGG

AAAGCTGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTA

AGTCCCGCAACGAGCGCAACCCTTGCTGTTAGTTGCTACGCAAGAGCACTCTAACAG

GACTGCCGTTGACAAAACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTT

ATGACCTGGGCTACACACGTACTACAATGGCCGTCAACAGAGGGAAGCAAGACCGCG

AGGTGGAGCAAACCCCCAAAAACGGCCCCAGTTCGGATTGTAGGCTGCAACCCGCCT

ACATGAAGTCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCC

CGGGCCTTGTACACACCGCCCGTCACACCATGGGAGCCGGTAATACCCGAAGTCAGT

AGCCTAACCGCAAGGAGGGCGCTGCCGAAGGTAGGATTGGCGACTGGGGTGAAGTC

GTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 105)

STS00008

Ruminococcaceae

ACGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAAG

unnamed sp 6
TCGAACGAGAATCTTTGAACAGATCTTTTCGGAGTGACGTTCAAAGAGGAAAGTGGC

GGACGGGCGAGTAACGCGTGAGTAACCTGCCCATAAGAGGGGGATAATCCATGGAA

ACGTGGACTAATACCGCATATTGTAGTTAAGTTGCATGACTTGATTATGAAAGATTTA

TCGCTTATGGATGGACTCGCGTCAGATTAGATAGTTGGTGAGGTAACGGCTCACCAA

GTCAACGATCTGTAGCCGAACTGAGAGGTTGATCGGCCGCATTGGGACTGAGACACG

GCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCGCAATGGGGGCAACCCTG

ACGCAGCAACGCCGCGTGCAGGAAGAAGGTCTTCGGATTGTAAACTGTTGTCGCAAG

GGAAGAAGACAGTGACGGTACCTTGTGAGAAAGTCACGGCTAACTACGTGCCAGCAG

CCGCGGTAATACGTAGGTGACAAGCGTTGTCCGGATTTACTGGGTGTAAAGGGCGCG

TAGGCGGACTGTCAAGTCAGTCGTGAAATACCGGGGCTTAACCCCGGGGCTGCGATT

GAAACTGACAGCCTTGAGTATCGGAGAGGAAAGCGGAATTCCTAGTGTAGCGGTGAA

ATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTTCTGGACGACAACTG

ACGCTGAGGCGCGAAAGTGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACA

CCGTAAACGATGGATACTAGGTGTAGGAGGTATCGACCCCTTCTGTGCCGCAGTTAAC

ACAATAAGTATCCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGA

CGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACC

TTACCTGGGCTTGACATCCCTGGAATCGAGTAGAGATACTTGAGTGCCTTCGGGAATC

AGGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTC

CCGCAACGAGCGCAACCCCTATTGTCAGTTGCCATCATTAAGTTGGGCACTCTGGCGA

GACTGCCGGTGACAAATCGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTT

ATGCCCAGGGCTACACACGTACTACAATGGCCGATAACAAAGTGCAGCGAAACCGTG

AGGTGGAGCGAATCACAAAACTCGGTCTCAGTTCAGATTGCAGGCTGCAACTCGCCT

GCATGAAGTTGGAATTGCTAGTAATCGCGGATCAGAATGCCGCGGTGAATACGTTCC

CGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTCGATAACACCCGAAGCCTGT

GAGCTAACCTTTAGGAGGCAGCAGTCGAAGGTGGGGTTGATGATTGGGGTGAAGTCG

TAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 106)

STS00009

Ruminococcaceae

ATTAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAA

unnamed sp 7
GTCGAACGAAGTTTCATAACGGAAGTTTTCGGATGGAAGATATGAAACTTAGTGGCG

GACGGGTGAGTAACACGTGAGCAACCTGCCTTTTAGAGGGGGATAACGTTTGGAAAC

GAACGCTAATACCGCATAACGTAGTCGATCGGCATCGATTGACTACCAAAGGAGCAA

TCCGCTGAAAGATGGGCTCGCGTCCGATTAGATAGTTGGCGGGGTAACGGCCCACCA

AGTCGACGATCGGTAGCCGGACTGAGAGGTTGATCGGCCACATTGGGACTGAGACAC

GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCT

GATGCAGCGACGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAAACCTCTGTCCTTG

GTGACGATAATGACGGTAGCCAAGGAGGAAGCCACGGCTAACTACGTGCCAGCAGCC

GCGGTAATACGTAGGTGGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGTA

GGCGGGAAAGCAAGTTGAATGTTTAAACTATCGGCTCAACCGATAATCGCGTTCAAA

ACTGTTTTTCTTGAGTGAAGTAGAGGTAGGCGGAATTCCTAGTGTAGCGGTGAAATGC

GTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCTTTAACTGACGC

TGAGGCTCGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGT

AAACGATGATTACTAGGTGTGGGGGGATCAACCCTTCCGTGCCGCAGCAAACGCAAT

AAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGG

ACCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACC

AGGTCTTGACATCCAACGAACTCGCTAGAGATAGCAAGGTGCCCTTCGGGGAGCGTT

GAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCC

GCAACGAGCGCAACCCTTACTGATAGTTGCTACGCAAGAGCACTCTATCGGGACTGC

CGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACC

TGGGCTACACACGTACTACAATGGCTATTAACAACGGGAAGCGAAGAGGTGACTCGG

AGCCAATCCAAAAAAATAGTCTCAGTTCGGATTGCAGGCTGCAACTCGCCTGCATGA

AGCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGTC

TTGTACACACCGCCCGTCACACCATGAGAGTTGGCAACACCCGAAGTCAGTAGTCTA

ACCGCAAGGAGGACGCTGCCGAAGGTGGGGTCGATGATTGGGGTGAAGTCGTAACA

AGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT (SEQ ID NO: 107)

REFERENCES

The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.

Callahan et al. 2016. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581-583.
Edgar, R. C. 2010. Search and clustering orders of magnitude faster than BLAST. Bioinforma. Oxf. Engl. 26, 2460-2461.
Edgar, R. C. 2013. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat. Methods 10, 996-998.
Frankel et al. 2017. Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia. 2017 October; 19(10):848-855. doi: 10.1016/j.neo.2017.08.004.
Gopalakrishnan et al. 2018. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science January 5; 359(6371):97-103. doi: 10.1126/science.aan4236.
Routy et al 2018. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018 Jan. 5; 359 (6371): 91-97. doi: 10.1126/science.aan3706.
Matson et al. 2018. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. January 5; 359(6371):104-108. doi: 10.1126/science.aao3290.
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Claims

1. A therapeutic composition comprising an effective amount of an isolated population of bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii.
2. A therapeutic composition comprising an effective amount of an isolated population of bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
3. The therapeutic composition of claim 2, wherein the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
4. A therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more genera within the family Ruminococcaceae, e.g., the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof.
5. A therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
6. A therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof.
7. A therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
8. A therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.
9. A therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
10. A therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
11. A therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof.
12. The therapeutic composition of any of claims 4-7, wherein the therapeutic composition comprises bacteria belonging to two or more genera.
13. The therapeutic composition of any of claims 4-7, wherein the therapeutic composition comprises bacteria belonging to three or more genera.
14. The therapeutic composition of any of claims 4-7, wherein the therapeutic composition comprises bacteria belonging to four or more genera.
15. The therapeutic composition of any of claims 5-7, wherein the therapeutic composition comprises bacteria belonging to five or more genera.
16. The therapeutic composition of any of claims 8-11, wherein the therapeutic composition comprises bacteria belonging to two or more species.
17. The therapeutic composition of any of claims 8-11, wherein the therapeutic composition comprises bacteria belonging to three or more species.
18. The therapeutic composition of any of claims 8-11, wherein the therapeutic composition comprises bacteria belonging to four or more species.
19. The therapeutic composition of any of claims 8-11, wherein the therapeutic composition comprises bacteria belonging to five or more species.
20. A therapeutic composition comprising an effective amount of a purified population of bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii.
21. A therapeutic composition comprising an effective amount of a purified population of bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
22. The therapeutic composition of claim 21, wherein the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
23. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof.
24. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
25. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof.
26. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
27. A therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.
28. A therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacteriumbiforme, Parabacteroides distasonis or combinations thereof.
29. A therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacteriumbiforme, Parabacteroides distasonis or combinations thereof.
30. A therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof.
31. The therapeutic composition of any of claims 23-26, wherein the therapeutic composition comprises bacteria belonging to two or more genera.
32. The therapeutic composition of any of claims 23-26, wherein the therapeutic composition comprises bacteria belonging to three or more genera.
33. The therapeutic composition of any of claims 23-26, wherein the therapeutic composition comprises bacteria belonging to four or more genera.
34. The therapeutic composition of any of claims 24-26, wherein the therapeutic composition comprises bacteria belonging to five or more genera.
35. The therapeutic composition of any of claims 27-30, wherein the therapeutic composition comprises bacteria belonging to two or more species.
36. The therapeutic composition of any of claims 27-30, wherein the therapeutic composition comprises bacteria belonging to three or more species.
37. The therapeutic composition of any of claims 27-30, wherein the therapeutic composition comprises bacteria belonging to four or more species.
38. The therapeutic composition of any of claims 27-30, wherein the therapeutic composition comprises bacteria belonging to five or more species.
39. The therapeutic composition of any one of claims 1-38, further comprising an anticancer agent.
40. The therapeutic composition of claim 39, wherein the anticancer agent is a checkpoint inhibitor.
41. The therapeutic composition of claim 40, wherein the checkpoint inhibitor is selected from an anti-PD-1 antibody, an anti-CTLA-4 antibody, an anti-PD-L1 antibody or combinations thereof.
42. The therapeutic composition of claim 41, wherein the checkpoint inhibitor is selected from pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, ipilimumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, BMS-936558, MK-3475, CT 011, MPDL3280A, MEDI-4736, MSB-0020718C, AUR-012, LAG-3, OX40 inhibitors, OX40L inhibitors, TIGIT inhibitors or STI-A1010.
43. The therapeutic composition of claim 39, wherein the anticancer agent is cyclophosphamide.
44. The therapeutic composition of any of claims 1-43, wherein each of the isolated populations of bacteria is present in the composition at a concentration of at least about 1×102 viable colony forming units.
45. The therapeutic composition of any of claims 1-44, wherein each isolated population of bacteria is present in the composition at a concentration of about 1×102 to 1×109 viable colony forming units.
46. The therapeutic composition of any of claims 1-45, wherein a fraction of the isolated population of bacteria comprises a spore-forming bacteria.
47. The therapeutic composition of any of claims 1-45, wherein a fraction of the isolated population of bacteria is in spore form.
48. The therapeutic composition of any of claims 1-47, wherein the composition further comprises a pharmaceutically acceptable excipient.
49. The therapeutic composition of any of claims 1-47, wherein the composition is formulated for delivery to the intestine.
50. The therapeutic composition of any of claims 1-47, wherein the composition is enterically coated.
51. The therapeutic composition of any of claims 1-47, wherein the composition is formulated for oral administration.
52. The therapeutic composition of claim 51, wherein the composition is formulated into a food or beverage.
53. The therapeutic composition of any of claims 1-52, wherein the composition can reduce the rate of tumor growth in an animal model.
54. The composition of any one of claims 1-53, wherein the composition is formulated for multiple administrations.
55. The composition of any one of claims 1-54, wherein each of the populations of bacteria is present in the composition at a concentration of at least 1×103 viable CFU.
56. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii.
57. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
58. The method of claim 57, wherein the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
59. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof.
60. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
61. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof.
62. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
63. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.
64. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
65. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
66. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of an isolated population of bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof.
67. The method of any of claims 59-62, wherein the therapeutic composition comprises bacteria belonging to two or more genera.
68. The method of any of claims 59-62, wherein the therapeutic composition comprises bacteria belonging to three or more genera.
69. The method of any of claims 59-62, wherein the therapeutic composition comprises bacteria belonging to four or more genera.
70. The method of any of claims 60-62, wherein the therapeutic composition comprises bacteria belonging to five or more genera.
71. The method of any of claims 63-66, wherein the therapeutic composition comprises bacteria belonging to two or more species.
72. The method of any of claims 63-66, wherein the therapeutic composition comprises bacteria belonging to three or more species.
73. The method of any of claims 63-66, wherein the therapeutic composition comprises bacteria belonging to four or more species.
74. The method of any of claims 63-66, wherein the therapeutic composition comprises bacteria belonging to five or more species.
75. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii.
76. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
77. The method of claim 76, wherein the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
78. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof.
79. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
80. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof.
81. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
82. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.
83. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
84. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
85. A method of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition comprising an effective amount of a purified population of bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof.
86. The method of any of claims 78-81, wherein the therapeutic composition comprises bacteria belonging to two or more genera.
87. The method of any of claims 78-81, wherein the therapeutic composition comprises bacteria belonging to three or more genera.
88. The method of any of claims 78-81, wherein the therapeutic composition comprises bacteria belonging to four or more genera.
89. The method of any of claims 79-81, wherein the therapeutic composition comprises bacteria belonging to five or more genera.
90. The method of any of claims 82-85, wherein the therapeutic composition comprises bacteria belonging to two or more species.
91. The method of any of claims 82-85, wherein the therapeutic composition comprises bacteria belonging to three or more species.
92. The method of any of claims 82-85, wherein the therapeutic composition comprises bacteria belonging to four or more species.
93. The method of any of claims 82-85, wherein the therapeutic composition comprises bacteria belonging to five or more species.
94. The method of any one of claims 56-93, further comprising administering an anticancer agent to the subject.
95. The method of claim 94, wherein the anticancer agent is a checkpoint inhibitor.
96. The method of claim 95, wherein the checkpoint inhibitor is selected from an anti-PD-1 antibody, an anti-CTLA-4 antibody, an anti-PD-L1 antibody or combinations thereof.
97. The method of claim 95, wherein the checkpoint inhibitor is selected from pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, ipilimumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, BMS-936558, MK-3475, CT 011, MPDL3280A, MEDI-4736, MSB-0020718C, AUR-012, LAG-3, OX40 inhibitors, OX40L inhibitors, TIGIT inhibitors, STI-A1010 or combinations thereof.
98. The method of claim 94, wherein the anticancer agent is cyclophosphamide.
99. The method of any of claims 56-98, wherein the isolated population of bacteria is administered at a concentration of at least about 1×102 viable colony forming units.
100. The method of any of claims 56-98, wherein the isolated population of bacteria is administered at a concentration of at a concentration of about 1×102 to 1×109 viable colony forming units.
101. The method of any of claims 56-100, wherein a fraction of the isolated population of bacteria comprises a spore-forming bacteria.
102. The method of any of claims 56-100, where a fraction of the isolated population of bacteria is in spore form.
103. The method of any of claims 56-102, wherein the composition further comprises a pharmaceutically acceptable excipient.
104. The method of any of claims 56-103, wherein the composition is formulated for delivery to the intestine.
105. The method of method of any of claims 56-103, wherein the composition is enterically coated.
106. The method of any of claims 56-102, wherein the composition is formulated for oral administration.
107. The method of claim 106, wherein the composition is formulated into a food or beverage.
108. The method of any of claims 56-107, wherein the mammalian subject is a human.
109. The method of any of claims 56-107, wherein the cancer is selected from metastatic melanoma, melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, Merkel cell skin cancer (Merkel cell carcinoma), or Hodgkin lymphoma.
110. The method of any of claims 56-109, wherein prior to administration of the isolated population of bacteria the subject is subjected to antibiotic treatment and/or a bowel cleanse.
111. The method of any one of claims 56-110, wherein the subject has previously been treated for the cancer.
112. The method of claim 111, wherein the subject has been determined to be a non-responder to the previous treatment.
113. The method of claim 111 or 112, wherein the subject has been determined to have a toxic response to the previous treatment.
114. The method of any one of claims 111-113, wherein the previous treatment comprises immune checkpoint blockade monotherapy or immune checkpoint blockade combination therapy.
115. The method of any one of claims 56-114, wherein the cancer is recurrent cancer.
116. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the genera of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii.
117. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the genera of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
118. The method of claim 117, wherein the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
119. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the genera of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof.
120. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the genera of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
121. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the genera of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof.
122. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the genera of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
123. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the species of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.
124. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the species of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
125. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the species of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
126. A method of identifying a mammalian subject as a candidate for immune checkpoint therapy in combination with adjuvant microbiome therapy, the method comprising: a) obtaining a microbiome sample from the subject,b) determining the prevalence of the species of bacteria in the microbiome sample, andc) determining that the subject is a candidate for the therapy if the microbiome sample comprises bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof.
127. The method of any of claims 116-126, wherein the subject is determined to be a candidate for immune checkpoint inhibitor therapy.
128. The method of any one of claims 116-127, wherein the wherein the immune checkpoint therapy comprises immune checkpoint blockade monotherapy or immune checkpoint blockade combination therapy.
129. The method of any of claims 116-126, wherein the subject is determined to be a candidate for cyclophosphamide therapy.
130. The method of any of claims 116-129, wherein the mammalian subject is a human.
131. The method of any of claims 116-130, wherein the cancer is selected from metastatic melanoma, melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, Merkel cell skin cancer (Merkel cell carcinoma), or Hodgkin lymphoma.
132. A therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to the genera Ruminococcus, Gemmiger, Faecalibacterium and Subdoligranulum.
133. A therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter and Parabacteroides.
134. A therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter and Parabacteroides.
135. A therapeutic composition comprising an effective amount of an isolated population of bacteria species Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacteriumbiforme and Parabacteroides distasonis.
136. A therapeutic composition comprising an effective amount of an isolated population of bacteria species Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus and Parabacteroides distasonis.
137. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Tables 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10 or 11.
138. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Tables 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10 or 11.
139. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to three or more of the species listed in Tables 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10 or 11.
140. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to four or more of the species listed in Tables 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B, 5A, 5B, 6A, 6B, 7A, 7B, 8A, 8B, 10 or 11.
141. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Table 1A.
142. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Table 1B.
143. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Table 10.
144. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the species listed in Table 11.
145. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Table 1A.
146. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Table 1B.
147. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Table 10.
148. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to two or more of the species listed in Table 11.
149. A therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the species in a clade selected from clade 101, clade 14, clade 126, clade 61, clade 125, clade 135, or combinations thereof.
150. A therapeutic composition comprising an effective amount of purified population of bacteria belonging to one or more of the species in a clade selected from clade 101, clade 14, clade 126, clade 61, clade 125, clade 135, or combinations thereof.
151. A therapeutic composition comprising an effective amount of an isolated population of bacteria belonging to one or more of the species in the phylogenetic tree of FIG. 6.
152. A therapeutic composition comprising an effective amount of a purified population of bacteria belonging to one or more of the species in the phylogenetic tree of FIG. 6.
153. A method of identifying a mammalian subject as a donor whose feces are useful for fecal matter transfer, the method comprising: a) obtaining a microbiome sample from the potential donor,b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, andc) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises bacterial species that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii.
154. A method of identifying a mammalian subject as a donor whose feces are useful for fecal matter transfer, the method comprising: a) obtaining a microbiome sample from the potential donor,b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, andc) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises bacterial species that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
155. The method of claim 154, wherein the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
156. A method of identifying a mammalian subject as a donor whose feces are useful for fecal matter transfer, the method comprising: a) obtaining a microbiome sample from the potential donor,b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, andc) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.
157. A method of identifying a mammalian subject as a donor whose feces are useful for fecal matter transfer, the method comprising: a) obtaining a microbiome sample from the potential donor,b) determining the prevalence and/or abundance of the species of bacteria in the microbiome sample, andc) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more of the bacteria species in one or more of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135.
158. A method of identifying a mammalian subject as a donor whose feces are useful for fecal matter transfer, the method comprising: a) obtaining a microbiome sample from the potential donor,b) determining the abundance of the species of bacteria in the microbiome sample, andc) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises bacterial species that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii.
159. A method of identifying a mammalian subject as a donor whose feces are useful for fecal matter transfer, the method comprising: a) obtaining a microbiome sample from the potential donor,b) determining the abundance of the species of bacteria in the microbiome sample, andc) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises bacterial species that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
160. The method of claim 159, wherein the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
161. A method of identifying a mammalian subject as a donor whose feces are useful for fecal matter transfer, the method comprising: a) obtaining a microbiome sample from the potential donor,b) determining the abundance of the species of bacteria in the microbiome sample, andc) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.
162. A method of identifying a mammalian subject as a donor whose feces are useful for fecal matter transfer, the method comprising: a) obtaining a microbiome sample from the potential donor,b) determining the abundance of the species of bacteria in the microbiome sample, andc) determining that the donor's feces is useful for fecal matter transfer if the microbiome sample comprises one or more of the bacteria species in one or more of clade 101, clade 14, clade 126, clade 61, clade 125 or clade 135.
163. A therapeutic composition derived from fecal matter from a donor identified using the method of any one of claims 153-162.
164. The therapeutic composition of claim 163, further comprising a pharmaceutically acceptable excipient.
165. The therapeutic composition of claim 163, wherein the therapeutic composition comprises bacteria that are in vegetative and/or spore form.
166. The therapeutic composition of claim 163, wherein the therapeutic composition further comprises a checkpoint inhibitor.
167. The therapeutic composition of claim 166, wherein the checkpoint inhibitor is selected from anti-PD-1 antibody, an anti-CTLA-4 antibody, an anti-PD-L1 antibody or combinations thereof.
168. The therapeutic composition of claim 166, wherein the checkpoint inhibitor is selected from pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, ipilimumab, pidilizumab, AMP-224, AMP-514, STI-A1110, TSR-042, RG-7446, BMS-936559, BMS-936558, MK-3475, CT 011, MPDL3280A, MEDI-4736, MSB-0020718C, AUR-012, LAG-3, OX40 inhibitors, OX40L inhibitors, TIGIT inhibitors, STI-A1010 or combinations thereof.
169. A of treating a cancer in a mammalian subject comprising administering to the subject a therapeutic composition of any one of claims 163-168.
170. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii.
171. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
172. The method of claim 171, wherein the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
173. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof.
174. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
175. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof.
176. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof.
177. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof.
178. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria species selected from Alistipes senegalensis, Barnesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
179. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof.
180. A method of treating cancer comprising administering an anticancer treatment to a subject determined to have a microbiome sample comprising bacteria species selected from Barnesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof178. A method comprising evaluating a microbiome profile for bacteria that are phylogenetic descendants of the most recent common ancestor (MRCA) of Faecalibacterium prausnitzii and Flavonifractor plautii in a sample from a subject.
181. A method comprising evaluating a microbiome profile for bacteria that have 16S rDNA sequence identity of at least 94.5% to 16S rDNA sequences of species belonging to the family Ruminococcaceae in a sample from a subject.
182. The method of claim 181, wherein the bacteria have 16S rDNA sequence identity of at least 98.7% to 16S rDNA sequences of species belonging to the family Ruminococcaceae.
183. A method comprising evaluating a microbiome profile for bacteria belonging to one or more of the genera Ruminococcus, Gemmiger, Faecalibacterium, Subdoligranulum or combinations thereof in a sample from the subject.
184. A method comprising evaluating a microbiome profile for bacteria belonging to one or more of the genera Alistipes, Bacteroides, Barnesiella, Bifidobacterium, Blautia, Clostridium, Eubacterium, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof in a sample from a subject.
185. A method comprising evaluating a microbiome profile for bacteria belonging to one or more of the genera Alistipes, Bacteroides, Blautia, Clostridium, Eubacterium, Parabacteroides or combinations thereof in a sample from a subject.
186. A method comprising evaluating a microbiome profile for one or more of the genera Barnesiella, Bifidobacterium, Blautia, Erysipelotrichaceae, Odoribacter, Parabacteroides or combinations thereof in a sample from a subject.
187. A method comprising evaluating a microbiome profile for bacteria species selected from Eubacterium siraeum, Clostridium leptum (GCF_000154345), Anaerotruncus colihominis, Subdoligranulum variabile, Clostridium methylpentosum, Pseudoflavonifractor capillosus, Ethanoligenens harbinense (GCF_000178115), Ruminococcus albus (GCF_000179635), Ruminococcus champanellensis (GCF_000210095), Flavonifractor plautii, Oscillibacter valericigenes, Oscillibacter ruminantium, Clostridium sporosphaeroides, Ruminococcus callidus, Ruminococcus flavefaciens (GCF_000518765), Clostridium jeddahense, Clostridium viride, Ruminococcus albus (GCF_000621285), Agathobaculum desmolans, Ruminococcus bicirculans, Ruthenibacterium lactatiformans, Clostridium phoceensis, Intestinimonas massiliensis, Anaeromassilibacillus senegalensis, Ruminococcus champanellensis (GCF_001312825), Bittarella massiliensis, Butyricicoccus porcorum, Acutalibacter muris, Clostridium leptum (GCF_002556665), Ruminococcus bromii (GCF_002834225, Monoglobus pectinilyticus, Ethanoligenens harbinense (GCF_003020045), Neglecta timonensis, Anaerotruncus rubiinfantis, Massilioclostridium coli, Angelakisella massiliensis, Sporobacter termitidis, Negativibacillus massiliensis, Massilimaliae massiliensis, Intestinibacillus massiliensis, Eubacterium coprostanoligenes, Provencibacterium massiliense, Papillibacter cinnamivorans, Clostridium merdae, Marasmitruncus massiliensis, Massilimaliae timonensis, Pygmaiobacter massiliensis, Clostridium minihomine, Neobitarella massiliensis, Faecalibacterium prausnitzii, Ruminococcus flavefaciens (GCF_000174895), Ruminococcaceae bacterium D16, Ruminococcus albus (GCF_000178155), Anaerotruncus sp_G3 2012, Oscillibacter sp 1 3, Clostridiales bacterium NK3B98, Oscillibacter sp KLE 1728, Firmicutes bacterium ASF500, Ruminococcus sp FC2018, Ruminococcus sp NK3A76, Ruminococcus flavefaciens (GCF_000701945), Ruminococcus sp HUN007, Bacterium MS4, Intestinimonas butyriciproducens, Oscillibacter sp ER4, Candidatus Soleaferrea massiliensis, Clostridium cellulosi, Clostridia bacterium UC5 1 2F7, Clostridia bacterium UC5 1 1E11, Clostridia bacterium UC5 1 1D1, Fournierella massiliensis, Clostridium sp W14A, Ruminococcaceae bacterium CPB6, Flavonifractor sp An92, Flavonifractor sp An91, Flavonifractor sp An306, Anaerofilum sp An201, Anaeromassilibacillus sp An200, Pseudoflavonifractor sp An187, Pseudoflavonifractor sp An184, Anaeromassilibacillus sp An172, Gemmiger sp An120, Flavonifractor sp An100, Flavonifractor sp An10, Eubacteriaceae bacterium CHKCI005, Ruminococcaceae bacterium P7, Ruminococcus bromii (GCF_900101355), Ruminococcus sp YE78, Ruminococcaceae bacterium FB2012, Ruminococcaceae bacterium Marseille P2935, Hydrogenoanaerobacterium saccharovorans, Ruminococcaceae bacterium D5, Oscillibacter sp PC13, Pseudoflavonifractor sp Marseille P3106, Neglecta sp Marseille P3890, Clostridium sp SN20, Anaerotruncus sp AT3, Anaeromassilibacillus sp Marseille P3876, Gemmiger formicilis (STS00001), Ruminococcaceae unnamed sp 1 (STS00002), Ruminococcaceae unnamed sp 2 (STS00003), Gemmiger formicilis (STS00004), Ruminococcaceae unnamed sp 3 (STS00005), Ruminococcaceae unnamed sp 4 (STS00006), Ruminococcaceae unnamed sp 5 (STS00007), Ruminococcaceae unnamed sp 6 (STS00008), Ruminococcaceae unnamed sp 7 (STS00009) or combinations thereof in a sample from a subject.
188. A method comprising evaluating a microbiome profile for bacteria species selected from Alistipes senegalensis, Bamesiella intestinihominis, Bacteroides dorei, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium_SC64, Clostridium innocuum, Odoribacter splanchnicus, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof in a sample from a subject.
189. A method comprising evaluating a microbiome profile for bacteria species selected from Alistipes senegalensis, Bacteroides dorei, Blautia_SC109, Clostridium_SC64, Eubacterium_biforme, Parabacteroides distasonis or combinations thereof in a sample from a subject.
190. A method comprising evaluating a microbiome profile for bacteria species selected from Bamesiella intestinihominis, Bifidobacterium bifidum, Bifidobacterium longum, Blautia_SC102, Blautia_SC109, Clostridium innocuum, Odoribacter splanchnicus, Parabacteroides distasonis or combinations thereof in a sample from a subject.
191. The method of any one of claims 181-190, wherein the method further comprises comparing the microbiome profile to a control microbiome.
192. The method of claim 191, wherein the control microbiome comprises a microbiome sample from a subject determined to be a responder to an anticancer treatment.
193. The method of claim 191, wherein the control microbiome comprises a microbiome sample from a subject determined to be a non-responder to an anticancer treatment.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/US 2019/024519, filed Mar. 28, 2019, which claims priority to U.S. Patent Application No. 62/649,453, filed Mar. 28, 2018, and 62/818,601, filed Mar. 14, 2019, each of which are incorporated herein by reference in their entirety.

PCT Information

Filing Document	Filing Date	Country	Kind
PCT/US2019/024519	3/28/2019	WO	00

Provisional Applications (2)

	Number	Date	Country
	62818601	Mar 2019	US
	62649453	Mar 2018	US

TREATMENT OF A CANCER BY MICROBIOME MODULATION

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Provisional Applications (2)