COMPOSITIONS AND METHODS FOR SUPPRESSING PATHOGENIC ORGANISMS

Information

  • Patent Application
  • 20240316119
  • Publication Number
    20240316119
  • Date Filed
    February 18, 2022
    2 years ago
  • Date Published
    September 26, 2024
    3 months ago
Abstract
Provided herein are compositions and methods for suppressing infection by pathogenic organisms. Also provided herein are compositions and methods for reducing or preventing colonization by pathogenic organisms and methods of treating infection by a pathogenic organism. Also provided herein are compositions comprising taurine and methods of using such compositions for suppressing infection by pathogenic organisms, preventing colonization by pathogenic organisms, and methods of treating infection pathogenic organisms.
Description
REFERENCE TO A SEQUENCE LISTING SUBMITTED AS A TEXT FILE VIA EFS-WEB

The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Feb. 17, 2022, is named P074570026WO00-SEQ-NTJ.txt, and is 157,149 bytes in size.


BACKGROUND

Multidrug resistant organisms (MDROs; “superbugs”), microorganisms that have developed resistance to one or more classes of antimicrobial agents, such as antibiotics, are emerging as serious global health threat. It is estimated that over 2 million people in the United States contract serious bacterial infections that are resistant to one or more antibiotics each year (CDC, Antibiotic Resistance Threats in the United States, 2013. Publication No. CS239559-B). Treatment options for subjects with MDROs are extremely limited; prevention of transmission is critical. The most important factor contributing to the generation and propagation of MDROs is the use and overuse/misuse of antibiotics and it is thought that the problem will increase in severity as further pathogenic organisms with antibiotic resistance arise (CDC, 2013; WHO 2017).


SUMMARY

In some aspects, the present disclosure provides compositions comprising two or more purified bacterial strains of species selected from the group consisting of a purified bacterial strain of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.


In some aspects, the present disclosure provides compositions comprising two or more purified bacterial strains, wherein the two or more purified bacterial strains comprise 16S rDNA sequences having at least 97% sequence identity with nucleic acid sequences selected from the group consisting of SEQ ID NOs: 1-47.


In some embodiments of the compositions provided herein, the composition comprises 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, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, or at least 47 purified bacterial strains.


In some aspects, the present disclosure provides compositions comprising purified bacterial strains of species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae. In some aspects, the present disclosure provides compositions comprising purified bacterial strains comprising 16S rDNA sequences having at least 97% sequence identity to nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36. In some embodiments of the compositions provided herein, the composition comprises bacterial strains that originate from more than one human donor. In some embodiments, any of the compositions described herein may further comprise taurine.


In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes or Bacteroidetes; one or more purified bacterial strains selected from the group consisting of an Escherichia species and a Fusobacterium species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes; one or more purified bacterial strains of Escherichia species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes; one or more purified bacterial strains of Fusobacterium species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Bacteroidetes; one or more purified bacterial strains of Escherichia species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Bacteroidetes; one or more purified bacterial strains of Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species, and one or more purified bacterial strains of species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species, and one or more purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, and Phascolarctobacterium faecium; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species and one or more purified bacterial strains of species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.


In some aspects, the present disclosure provides compositions comprising purified bacterial strain belonging to Fusobacterium species and one or more purified bacterial strains of species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species, and one or more purified bacterial strains of species selected from the group consisting of Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species and one or more purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Fusobacterium species and one or more purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species; and taurine.


In some aspects, the present disclosure provides compositions comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613), cf. Clostridium sp. MLG055 (Erysipelotrichaceae bacterium 2_2_44A), Clostridium indolis (Anaerostipes caccae DSM 14662), Anaerotruncus colihominis (Anaerotruncus colihominis DSM 17241), Ruminococcus sp. ID8 (Lachnospiraceae bacterium 2_1_46FAA), Clostridium lavalense (Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp. D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp. 316002/08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613), cf. Clostridium sp. MLG055 (Erysipelotrichaceae bacterium 2_2_44A), Clostridium indolis (Anaerostipes caccae DSM 14662), Anaerotruncus colihominis (Anaerotruncus colihominis DSM 17241), Ruminococcus sp. ID8 (Lachnospiraceae bacterium 2_1_46FAA), Clostridium lavalense (Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp. D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp. 316002/08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), a purified bacterial strain belonging to Escherichia species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613), cf. Clostridium sp. MLG055 (Erysipelotrichaceae bacterium 2_2_44A), Clostridium indolis (Anaerostipes caccae DSM 14662), Anaerotruncus colihominis (Anaerotruncus colihominis DSM 17241), Ruminococcus sp. ID8 (Lachnospiraceae bacterium 2_1_46FAA), Clostridium lavalense (Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp. D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp. 316002/08 (Clostriales 3_1_57FAA_CT1), a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecis, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Alistipes shahii, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecis, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Alistipes putredinis, Alistipes shahii, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii;


and taurine.


In some aspects, the present disclosure provides compositions comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Clostridium clostridioforme, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.


In some aspects, the present disclosure provides compositions comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.


In some aspects, the present disclosure provides compositions comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Clostridium citroniae, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising bacterial strains of species Bacteroides vulgatus, Clostridium citroniae, and Phascolarctobacterium faecium, and one or more purified bacterial strains of species selected from the group consisting of Bacteroides faecis, Bacteroides ovatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides faecis, Bacteroides vulgatus, Odoribacter splanchnicus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.


In some aspects, the present disclosure provides compositions comprising purified bacterial strains of species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae; and taurine. In some aspects, the present disclosure provides compositions comprising purified bacterial strains comprising 16S rDNA sequences having at least 97% sequence identity to the nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36; and taurine.


In some embodiments, any of the compositions described herein may further comprise one or more bacterial strain selected from the group consisting of Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.


In some embodiments, the composition further comprises taurine. In some embodiments, the composition comprises between about 40 mg to about 3000 mg taurine. In some embodiments, the composition comprises between about 100 mg to about 2000 mg taurine. In some embodiments, the composition comprises between about 500 mg to about 1500 mg taurine.


In some embodiments, the composition is effective in suppressing the replication, survival, and/or colonization of one or more pathogenic organisms. In some embodiments, the composition is effective in treating an infection by a pathogenic organism in a subject. In some embodiments, the pathogenic organism is susceptible to antibiotics. In some embodiments, the pathogenic organism is resistant to one or more antibiotics. In some embodiments, the pathogenic organism is a multi-drug resistant organism.


In some embodiments, the multi-drug resistant organism is Carbapenem Resistant Enterobacteriaceae (CRE) or Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. In some embodiments, the Carbapenem Resistant Enterobacteriaceae (CRE) is carbapenem-resistant Klebsiella pneumoniae. In some embodiments, the carbapenem-resistant Klebsiella pneumoniae is carbapenem-resistant Klebsiella pneumoniae ATCC 700721. In some embodiments, the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae or EBSL-producing E. coli. In some embodiments, the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae subsp. pneumoniae (ATCC 700721), ESBL-producing E. coli ATCC BAA 2777, adherent/invasive E. coli (AIEC), Shiga toxin-producing E. coli (STEC), Verocytotoxin-producing E. coli (VTEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), or diffusely adherent E. coli (DAEC).


In some embodiments, the bacterial strains are lyophilized. In some embodiments, the bacterial strains are spray-dried. In some embodiments, one or more of the bacterial strains are in spore form. In some embodiments, each of the bacterial strains is in spore form. In some embodiments, one or more of the bacterial strains are in vegetative form. In some embodiments, each of the bacterial strains is in vegetative form. In some embodiments, the composition further comprises one or more enteric polymers.


In some embodiments, the pharmaceutical composition comprises between 1×106 and 1×1010 colony forming units (CFUs) per bacterial strain. In some embodiments, each bacterial strain is present in the composition in the same CFU quantities (e.g., each strain is present at 1×108 CFU).


In some aspects, the present disclosure provides pharmaceutical compositions comprising any of the compositions described herein and a pharmaceutically acceptable excipient.


In some embodiments, the pharmaceutical composition is formulated for oral delivery. In some embodiments, the pharmaceutical composition is formulated for delivery to the intestine. In some embodiments, the pharmaceutical composition is formulated for delivery to the colon. In some embodiments, the pharmaceutical composition is administered as one dose. In some embodiments, the pharmaceutical composition is administered as multiple doses. In some embodiments, each dose comprises the administration of multiple capsules.


In some aspects, the present disclosure provides a food product comprising any of the compositions comprising bacterial strains provided herein, and a nutrient.


In some aspects, the present disclosure provides a method of suppressing infection by a pathogenic organism in a subject, comprising administering to the subject a therapeutically effective amount of any of the compositions comprising bacterial strains, pharmaceutical compositions, or food products described herein.


In some aspects, the present disclosure provides a method of reducing or preventing colonization by a pathogenic organism in a subject, comprising administering to the subject a therapeutically effective amount of any of the compositions comprising bacterial strains, pharmaceutical compositions, or food products described herein.


In some aspects, the present disclosure provides a method of treating infection by a pathogenic organism in a subject, comprising administering to the subject a therapeutically effective amount of any of the compositions comprising bacterial strains, pharmaceutical compositions, or food products described herein.


In some embodiments of the methods provided herein, the pathogenic organism is a multi-drug resistant organism. In some embodiments, the pathogenic organism is Klebsiella pneumoniae. In some embodiments, the Klebsiella pneumoniae is multi-drug resistant. In some embodiments, the multi-drug resistant Klebsiella pneumoniae is carbapenem-resistant Klebsiella pneumoniae.


In some embodiments, the pathogenic organism is Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. In some embodiments, the ESBL producing Enterobacteriaceae is Escherichia coli (E. coli). In some embodiments, the E. coli is adherent/invasive E. coli (AIEC), Shiga toxin-producing E. coli (STEC), Verocytotoxin-producing E. coli (VTEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), or diffusely adherent E. coli (DAEC).


In some embodiments, the subject is human. In some embodiments, the composition is administered to the subject by oral administration. In some embodiments, the composition is administered to the subject by rectal administration. In some embodiments, the administering suppresses the replication, survival, and/or colonization of the pathogenic organism. In some embodiments, the administration of the composition is not preceded by administration of vancomycin. In some embodiments, further comprising administering an antibiotic to the subject prior to administration of the composition. In some embodiments, the antibiotic is vancomycin.


In some embodiments, the method further comprises administering a composition comprising taurine to the subject. In some embodiments, the composition comprising taurine is administered to the subject prior to or after administration of any of the compositions or food products described herein containing a purified bacterial mixture. In some embodiments, the subject is administered between about 40 mg to about 3000 mg taurine per day. In some embodiments, the subject is administered between about 100 mg to about 2000 mg taurine per day. In some embodiments, the subject is administered between about 500 mg to about 1500 mg taurine per day.





BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings are not intended to be drawn to scale. The figures are illustrative only and are not required for enablement of the disclosure. For purposes of clarity, not every component may be labeled in every drawing. In the drawings:



FIG. 1 presents a timeline of an exemplary mouse model of carbapenem-resistant Enterobacteriaceae (“CRE”) or extended spectrum beta-lactamase-producing Enterobacteriaceae (“ESBL”) colonization experiment.



FIG. 2 shows extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae colonization (colony forming units, “CFU”) levels in mice at 14 days post-treatment (“D14 post Tx”). From left to right, control (PBS), a composition of 36 bacterial strains (“36-mix”), or stool fraction from a human donor (Donor 1 “SFL”). Dashed line represents the limit of detection.



FIG. 3 is a table showing the phylum, family, and species names of the bacterial strains present in a composition of 47 bacterial strains, referred to herein as “47-mix.”



FIG. 4 shows carbapenem-resistant Klebsiella pneumoniae (CRE) or extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae colonization (colony forming units, “CFU”) levels in mice at 14 days post-treatment (“D14 post Tx”). Mice were treated with control (PBS) or a composition of 47 bacterial strains. For each treatment, data points in the left column represent CRE colonization, and data points in the right column represent ESBL colonization, L.o.D. (dashed line) represents the limit of detection.



FIGS. 5A and 5B show ESBL-producing Enterobacteriaceae and carbapenem-resistant Klebsiella pneumoniae (CRE) colonization in mice treated with the indicated compositions. FIG. 5A shows extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae colonization (colony forming units, “CFU”) levels in mice at 7, 10, and 14 days post-treatment (“days post Tx”). FIG. 5B shows CRE colonization (colony forming units, “CFU”) levels in mice at 7, 10, and 14 days post-treatment (“days post Tx”). For each time point, data are shown from left to right from mice treated with control (PBS), a composition of 47 strains (47-mix), a stool fraction from a second human donor (Donor 2 “SFL”), or a bacterial composition obtained by introducing fecal matter from a first human donor into a germ-free mouse and obtaining stool from the mouse to prepare a fecal matter transplant (Donor 1-inoculated mouse FMT). The dashed line represents the limit of detection.





DETAILED DESCRIPTION

Suppressing or preventing undesired bacteria in a subject or suppressing or preventing colonization of bacteria in a particular region of the body can be challenging. Bacterial colonization may induce immune responses (local or systemic) in the subject, which may lead to serious disease. In particular, for multi-drug resistant organisms, or organisms that have acquired antibiotic resistance, elimination with many conventional therapeutics, such as antibiotics, may not be possible due to resistance or tolerance to the therapeutic. Additionally, it has been recently appreciated that intestinal colonization by bacteria of the oral microbiome may influence the immune environment of the intestine, such as induce Th1-dominated immune responses and lead to chronic inflammation and inflammatory conditions (see, e.g., Atarashi et al. Science (2017) 358 (359-365)). Normal bacterial colonization of different regions of the body, such as the oral cavity, may provide a reservoir of bacteria that can migrate and colonize other regions, such as the intestines.


Development of a live biotherapeutic product that is effective in promoting intestinal decolonization against multiple pathogens (e.g., both carbapenem-resistant Enterobacteriaceae and extended spectrum beta-lactamase-producing Enterobacteriaceae) has been challenging. Provided herein are compositions and methods for reducing/suppressing and/or preventing colonization by pathogenic organisms, such as multi-drug resistant organisms, for example carbapenem resistant Enterobacteriaceae (CRE) and extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Provided herein are compositions and methods for suppressing infection by pathogenic organisms. Provided herein are compositions and methods for treating infection by a pathogenic organism. Also provided herein are compositions and methods for inducing regulatory T cell (Treg) production in response to pathogenic organisms. Provided herein are compositions and methods for inducing production of short chain fatty acids (SCFAs) in response to pathogenic organisms. Also provided herein are compositions comprising purified bacterial mixture and taurine, which may further aid in the colonization of the microbiota by beneficial bacterial strains and/or reduction in colonization (resistance) to pathogens.


In some embodiments, the one or more of the bacterial strains of the compositions provided herein colonize or recolonize the intestinal tract or parts of the intestinal tract (e.g., the colon or the cecum) of the subject. Such colonization or recolonization may also be referred to as grafting. In some embodiments, the one or more of the bacterial strains of the compositions recolonize the intestinal tract (e.g., the colon or the cecum) of the subject, for example after another organism or population of organisms has been partially or completely removed (e.g., by antibiotic treatment). In some embodiments, one or more of the bacterial strains of the compositions recolonize the intestinal tract (e.g., the colon or the cecum) after one or more pathogenic organisms or other organism (e.g., bacteria that induce an immune response) has been removed. In some embodiments, the recolonization of the intestinal tract or parts thereof by the bacterial strains of the compositions described herein prevents or suppresses colonization by undesired organisms (e.g., pathogenic organisms, multi-drug resistant organisms, oral microbiome bacteria, bacteria that induce immune responses, pathobionts, bacteria that reduce Treg production, bacteria that reduce SCFA production).


In some embodiments, the one or more of the bacterial strains of the compositions can “outgrow” a pathogen or undesired bacteria, such as a pathogenic organism, for example carbapenem resistant Enterobacteriaceae (CRE) and/or extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Thus, in some embodiments, if a pathogen or undesired bacteria (e.g., pathogenic organisms, multi-drug resistant organism, for example carbapenem resistanct Enterobacteriaceae (CRE) and extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae) and one or more bacteria of compositions provided herein are both present in the intestinal tract (e.g., the colon or the cecum), the one or more bacteria of compositions provided herein grow faster (e.g., have a shorter doubling time) than the pathogen, thereby preventing the pathogen from accumulating in the intestinal tract (e.g., the colon or the cecum). In some embodiments, the one or more bacteria of compositions provided herein grow faster than the pathogen in an otherwise intact or complete microbiome. In some embodiments, the one or more bacteria of compositions provided herein grow faster than the pathogen in a depleted microbiome (e.g., following antibiotic treatment). In some embodiments, the faster growth results because the one or more bacteria of the compositions provided herein are better at grafting in the intestinal tract (e.g., the colon or the cecum). In some embodiments, the faster growth results because the one or more bacteria of the compositions provided herein are better at metabolizing nutrients present in the intestinal tract (e.g., the colon or the cecum). In some embodiments, the compositions of bacterial strains provided herein prevent or inhibit replication of the pathogen. In some embodiments, the compositions of bacterial strains provided herein induce death of (kill) the pathogen. In some embodiments, the bacterial strains of the compositions provided herein can treat pathogenic infections, because of the synergy between the bacterial strains.


In some embodiments, the bacterial compositions described herein prevent recolonization by a pathogen or undesired bacteria (e.g., pathogenic organisms, multi-drug resistant organisms, for example carbapenem resistanct Enterobacteriaceae (CRE) and extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae). For example, in some embodiments, the pathogen or undesired bacteria have been reduced or eliminated from the subject, for example, using a first therapeutic agent (such as an antibiotic), and the bacterial compositions described herein are administered to prevent recolonization of the subject. In some embodiments, the bacterial compositions described herein reduce or eliminate a pathogen or undesired bacteria from the subject and prevent recolonization of the subject.


In some embodiments, the combination of bacterial strains of the compositions provided herein is superior in the use of nutrients when compared to the pathogen or undesired bacteria, thereby suppressing the growth of the pathogen or undesired bacteria. In some embodiments, the combination of bacterial strains of the compositions provided herein is superior in grafting when compared to the pathogen or undesired bacteria, thereby suppressing the growth of the pathogen or undesired bacteria. In some embodiments, the combination of bacterial strains of the compositions provided herein is superior in the use of nutrients and in grafting when compared to the pathogen or undesired bacteria, thereby suppressing the growth of the pathogen or undesired bacteria. In some embodiments, the combination of bacterial strains of the compositions provided herein inhibits the growth, survival, and/or colonization of the pathogen or undesired bacteria.


In some embodiments, the combination of bacterial strains of the compositions provided herein has antagonizing or inhibitory activity towards the pathogen or undesired bacteria, thereby inhibiting the growth, survival, and/or colonization of the pathogen or undesired bacteria. In some embodiments, at least one bacterial strain of the compositions provided herein has antagonizing or inhibitory activity towards the pathogen or undesired bacteria, thereby inhibiting the growth, survival, and/or colonization of the pathogen or undesired bacteria.


In some embodiments, the bacterial strains of the compositions provide a synergistic effect in colonizing specific niches in the intestinal tract (e.g., the colon or the cecum). In some embodiments, the synergistic effect is provided by the capacity of the combination to metabolize specific nutrients. In some embodiments, the synergistic effect is provided by the capacity of the combination to provide specific metabolites to the environment.


The bacterial strains used in the compositions provided herein generally are isolated from the microbiome of healthy individuals. In some embodiments, the compositions include strains originating from a single individual. In some embodiments, the compositions include strains originating from multiple individuals. In some embodiments, the bacterial strains are obtained from multiple individuals, isolated, and grown up individually. The bacterial compositions that are grown up individually may subsequently be combined to provide the compositions of the disclosure. It should be appreciated that the origin of the bacterial strains of the compositions provided herein is not limited to the human microbiome from a healthy individual. In some embodiments, the bacterial strains originate from a human with a microbiome in dysbiosis. In some embodiments, the bacterial strains originate from non-human animals or the environment (e.g., soil or surface water). In some embodiments, the combinations of bacterial strains provided herein originate from multiple sources (e.g., human and non-human animals).


In some embodiments, the bacteria of the compositions provided herein are anaerobic bacteria. In some embodiments, the bacteria of the compositions provided herein are obligate anaerobic bacteria.


In general, bacterial strains may be classified phylogenetically with other closely related strains and species based on their 16S rRNA (or 16S rDNA) nucleic acid sequence. Methods for determining the identity of specific bacterial species based on their 16S rRNA (or 16S rDNA) nucleic acid sequence are well known in the art (See, e.g., Jumpstart Consortium Human Microbiome Project Data Generation Working, G. PLOS One (2012) 7, e39315).


It should be appreciated that any of the compositions described herein may contain multiple strains of a particular bacterial species. For example, in some embodiments, the composition may comprise two strains of the species Absiella innocuum.


The disclosure encompasses compositions comprising bacterial strains having close sequence identity or homology to and/or fall within the species of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Clostridium bifermentans, Paeniclostridium sordellii, Clostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium citroniae, Clostridium_M clostridioforme, Clostridium clostridioforme, Eubacterium_E hallii, Eubacterium hallii, Agathobacter rectale, Eubacterium rectale, Blautia producta, Blautia_A obeum, Blautia obeum Dorea longicatena, Coprococcus_B comes, Coprococcus comes, Anaerostipes caccae, Agathobaculum sp, Agathobaculum buryriciproducens, Phascolarctobacterium faecium, Escherichia coli, Escherichia sp. 3_2_53FAA, Fusobacterium_A sp, Fusobacterium sp, Fusobacterium mortiferum, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.


In some embodiments, the compositions disclosed herein comprise two or more bacterial strains. In some embodiments, the compositions described herein 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, or at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47 or more bacterial strains (e.g., purified bacterial strains).


It should be appreciated that the terms “bacteria” and “bacterial strains” as used herein are interchangeable. The compositions described herein containing multiple purified bacterial strains may also be referred to as “live bacterial products.”


In one aspect, the disclosure provides a live bacterial product referred to as “47-mix” (see, FIGS. 3-5). As shown in FIG. 3 and Table 1, the composition referred to as the 47-mix contains 47 bacterial strains related to the following species: Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions comprise two or more (e.g., 2, 3, 4, 5, or more) purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions consist of two or more (e.g., 2, 3, 4, 5, or more) bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.


In some embodiments, the compositions consist essentially of two or more (e.g., 2, 3, 4, 5, or more) bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions comprise bacterial strains of species Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions consist of bacterial strains of species Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions consist essentially of bacterial strains of species Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine. In some embodiments, consisting essentially of, as used herein, refers to compositions that do not include any additional therapeutically active bacterial strains.


In some embodiments, the compositions comprise 38 bacterial strains, which may be referred to as a “38-mix.” In some embodiments, the compositions comprise 38 bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions consist of 38 bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions consist essentially of 38 bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions comprise 33 bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions consist of 33 bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some embodiments, the compositions consist essentially of 33 bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri. In some embodiments, the composition further comprises taurine.


In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes or Bacteroidetes; one or more purified bacterial strains selected from the group consisting of an Escherichia species and a Fusobacterium species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes; one or more purified bacterial strains of Escherichia species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Firmicutes; one or more purified bacterial strains of Fusobacterium species; and taurine.


The Firmicutes phylum, also referred to as the phylum Bacillota, is a phylum of Gram-positive bacteria, many of which are spore-forming. Classes within the Firmicutes phylum include the obligate anaerobe class Clostridia, and Bacilli, which may be obligate or facultative anaerobes. In some embodiments of compositions comprising a purified bacterial strain belonging to the phylum Firmicutes, the bacterial strain belongs to a class selected from the group consisting of Bacilli, Clostridia, and Negativicutes. In some embodiments, the composition comprises two or more bacterial strains belonging to the phylum Firmicutes, and each of the bacterial strains independently belongs to a class selected from the group consisting of Bacilli, Clostridia, and Negativicutes.


Families within the Firmicutes phylum include Peptostreptococcaceae, Erysipelatotrichiaceae, Lachnospiraceae, Ruminococcaceae, Acidaminococcaceae, and Clostridiaceae. In some embodiments of compositions comprising a purified bacterial strain belonging to the phylum Firmicutes, the bacterial strain belongs to a family selected from the group consisting of Peptostreptococcaceae, Erysipelatotrichiaceae, Lachnospiraceae, Ruminococcaceae, Acidaminococcaceae, and Clostridiaceae. In some embodiments, the composition comprises two or more bacterial strains belonging to the phylum Firmicutes, and the two or more bacterial strains independently belong to a family independently selected from the group consisting of Peptostreptococcaceae, Erysipelatotrichiaceae, Lachnospiraceae, Ruminococcaceae, Acidaminococcaceae, and Clostridiaceae. In some embodiments, each of the bacterial strains belonging to the phylum Firmicultes independently belongs to a family selected from the group consisting of Peptostreptococcaceae, Erysipelatotrichiaceae, Lachnospiraceae, Ruminococcaceae, Acidaminococcaceae, and Clostridiaceae.


The Bacteroidetes phylum, also referred to as the Bacteroidota phylum, is a phylum of Gram-negative, non-spore-forming bacteria, which may be aerobic or anaerobic. Classes within the Bacteroidetes phylum include Bacteroidia, Chitinophagia, Cytophagia, Flavobacteria, Saprospiria, and Sphingobacteriia. In some embodiments of compositions comprising a purified bacterial strain belonging to the phylum Bacteroidetes, the bacterial strain belongs to the class Bacteroidia. In some embodiments, the composition comprises two or more bacterial strains belonging to the phylum Bacteroidetes, and two or more of the bacterial strains belong to the class Bacteroidia. In some embodiments, each of the bacterial strains of the composition belonging to the phylum Bacteroidetes belongs to the class Bacteroidia.


Families within the Bacteroidetes phylum include Bacteroidaceae, Marinifilaceae, Tannerellaceae, Rikenellaceae, Porphyromonadaceae, Odorbacteraceae, and Prevotellaceae. In some embodments of compositions comprising a purified bacterial strain belonging to the phylum Bacteroidetes, the bacterial strain belongs to a family selected from the group consisting of Bacteroidaceae, Marinifilaceae, Tannerellaceae, Rikenellaceae, Porphyromonadaceae, Odorbacteraceae, and Prevotellaceae. In some embodiments, the composition comprises two or more bacterial strains belonging to the phylum Bacteroidetes, and the two or more bacterial strains belongs to a family independently selected from the group consisting of Bacteroidaceae, Marinifilaceae, Tannerellaceae, Rikenellaceae, Porphyromonadaceae, Odorbacteraceae, and Prevotellaceae.


In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Bacteroidetes; one or more purified bacterial strains of Escherichia species; and taurine. In some aspects, the present disclosure provides compositions comprising one or more purified bacterial strains belonging to the phylum Bacteroidetes; one or more purified bacterial strains of Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species, and one or more purified bacterial strains of species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species, and one or more purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, and Phascolarctobacterium faecium; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species and one or more purified bacterial strains of species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Fusobacterium species and one or more purified bacterial strains of species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species, and one or more purified bacterial strains of species selected from the group consisting of Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Escherichia species and one or more purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial strain belonging to Fusobacterium species and one or more purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species; and taurine.


In some aspects, the present disclosure provides compositions comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613), cf. Clostridium sp. MLG055 (Erysipelotrichaceae bacterium 2_2_44A), Clostridium indolis (Anaerostipes caccae DSM 14662), Anaerotruncus colihominis (Anaerotruncus colihominis DSM 17241), Ruminococcus sp. ID8 (Lachnospiraceae bacterium 2_1_46FAA), Clostridium lavalense (Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp. D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp. 316002/08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613), cf. Clostridium sp. MLG055 (Erysipelotrichaceae bacterium 2_2_44A), Clostridium indolis (Anaerostipes caccae DSM 14662), Anaerotruncus colihominis (Anaerotruncus colihominis DSM 17241), Ruminococcus sp. ID8 (Lachnospiraceae bacterium 2_1_46FAA), Clostridium lavalense (Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp. D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp. 316002/08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), a purified bacterial strain belonging to Escherichia species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium boltede ATCC BAA-613), cf. Clostridium sp. MLG055 (Erysipelotrichaceae bacterium 2_2_44A), Clostridium indolis (Anaerostipes caccae DSM 14662), Anaerotruncus colihominis (Anaerotruncus colihominis DSM 17241), Ruminococcus sp. ID8 (Lachnospiraceae bacterium 2_1_46FAA), Clostridium lavalense (Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp. D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp. 316002/08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species; and taurine.


In some aspects, the present disclosure provides compositions comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecis, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Alistipes shahii, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecis, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Alistipes putredinis, Alistipes shahii, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.


In some aspects, the present disclosure provides compositions comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.


In some aspects, the present disclosure provides compositions comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Clostridium clostridioforme, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.


In some aspects, the present disclosure provides compositions comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.


In some aspects, the present disclosure provides compositions comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Clostridium citroniae, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising bacterial strains of species Bacteroides vulgatus, Clostridium citroniae, and Phascolarctobacterium faecium, and one or more purified bacterial strains of species selected from the group consisting of Bacteroides faecis, Bacteroides ovatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides faecis, Bacteroides vulgatus, Odoribacter splanchnicus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.


In some aspects, the present disclosure provides compositions comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.


In some aspects, the present disclosure provides compositions comprising a purified bacterial mixture comprising bacterial strains of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae. In some aspects, the disclosure provides compositions comprising a purified bacterial mixture consisting of bacterial strains of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae. In some aspects, the present disclosure provides compositions comprising bacterial strains of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae; and taurine. In some aspects, the disclosure provides a composition comprising taurine and a purified bacterial mixture consisting of bacterial strains of the species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae. In some embodiments, a bacterial strain of Bacteroides faecis comprises a 16S rDNA sequence comprising at least 97% sequence identity to the nucleic acid sequence of SEQ ID NO: 30. In some embodiments, a bacterial strain of Bacteroides vulgatus comprises a 16S rDNA sequence comprising at least 97% sequence identity to the nucleic acid sequence of SEQ ID NO: 10. In some embodiments, a bacterial strain of Phascolartcobacterium faecium comprises a 16S rDNA sequence comprising at least 97% sequence identity to the nucleic acid sequence of SEQ ID NO: 36. In some embodiments, a bacterial strain of Clostridium citroniae comprises a 16S rDNA sequence comprising at least 97% sequence identity to the nucleic acid sequence of SEQ ID NO: 29.


In some aspects, the present disclosure provides compositions comprising purified bacterial strains comprising 16S rDNA sequences having at least 97% sequence identity to nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36. In some aspects, the present disclosure provides compositions comprising purified bacterial strains comprising 16S rDNA sequences having at least 97% sequence identity to nucleic acid sequences of SEQ ID NOS: 10, 29, 30, and 36; and taurine. In some aspects, the present disclosure provides compositions comprising a purified bacterial mixture consisting of bacterial strains comprising 16S rDNA sequences having at least 97% sequence identity to the nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36. In some aspects, the present disclosure provides compositions comprising taurine and a purified bacterial mixture consisting of bacterial strains comprising 16S rDNA sequences having at least 97% sequence identity to the nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36.


In some embodiments, any of the compositions described herein further comprises one or more bacterial strain selected from the group consisting of Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.


As will be appreciated by one of skill in the art, any one or more bacterial strain identified as having pathogen-antagonizing activity may be included in any of the compositions described herein.


Aspects of the disclosure relate to bacterial strains with 16S rDNA sequences that have sequence identity to a nucleic acid sequence of any one of the sequences of the bacterial strains or species described herein. The terms “identical,” or percent “identity,” in the context of two or more nucleic acids or amino acid sequences, refer to two or more sequences or subsequences that are the same. Two sequences are “substantially identical” if two sequences have a specified percentage of amino acid residues or nucleotides that are the same (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8% or 99.9% sequence identity) over a specified region of a nucleic acid or amino acid sequence or over the entire sequence, when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, the identity exists over a region that is at least about 50 nucleotides in length, or more preferably over a region that is 100 to 500 or 1000 or more nucleotides in length. In some embodiments, the identity exists over the length the 16S rRNA or 16S rDNA sequence.


In some embodiments, the bacterial strain has at least 60%, at least 70%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or up to 100% sequence identity relative to any of the strains or bacterial species described herein over a specified region or over the entire sequence. It would be appreciated by one of skill in the art that the term “sequence identity” or “percent sequence identity,” in the context of two or more nucleic acid sequences or amino acid sequences, refers to a measure of similarity between two or more sequences or portion(s) thereof.


Additionally, or alternatively, two or more sequences may be assessed for the alignment between the sequences. The terms “alignment” or percent “alignment” in the context of two or more nucleic acids or amino acid sequences, refer to two or more sequences or subsequences that are the same. Two sequences are “substantially aligned” if two sequences have a specified percentage of amino acid residues or nucleotides that are the same (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8% or 99.9% identical) over a specified region or over the entire sequence, when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, the alignment exists over a region that is at least about 50 nucleotides in length, or more preferably over a region that is 100 to 500 or 1000 or more nucleotides in length. In some embodiments, the identity exists over the length the 16S rRNA or 16S rDNA sequence.


For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. Methods of alignment of sequences for comparison are well known in the art. See, e.g., by the local homology algorithm of Smith and Waterman (1970) Adv. Appl. Math. 2:482c, by the homology alignment algorithm of Needleman and Wunsch, J. Mol. Biol. (1970) 48:443, by the search for similarity method of Pearson and Lipman. Proc. Natl. Acad. Sci. USA 85:2444, 1988, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group. Madison. WI), or by manual alignment and visual inspection (sec. e.g., Brent et al., Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (Ringbou ed., 2003)). Two examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., Nuc. Acids Res. 25:3389-3402, 1977; and Altschul et al., J. Mol. Biol. 215:403-410, 1990, respectively.


In one aspect, the bacterial composition comprises two or more (e.g., 2, 3, 4, 5 or more) purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99.%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with the nucleic acid sequence selected from SEQ ID NOs: 1-83. In one aspect, the bacterial composition consists of two or more (e.g., 2, 3, 4, 5 or more) purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%. 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with the nucleic acid sequence selected from SEQ ID NOs: 1-83. In one aspect, the bacterial composition consists essentially of two or more (e.g., 2, 3, 4, 5 or more) purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with the nucleic acid sequence selected from SEQ ID NOs: 1-83.


In one aspect, the bacterial composition comprises two or more (e.g., 2, 3, 4, 5 or more) purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with the nucleic acid sequence selected from SEQ ID NOs: 1-47. In one aspect, the bacterial composition consists of two or more (e.g., 2, 3, 4, 5 or more) purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%. 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with the nucleic acid sequence selected from SEQ ID NOs: 1-47. In one aspect, the bacterial composition consists essentially of two or more (e.g., 2, 3, 4, 5 or more) purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with the nucleic acid sequence selected from SEQ ID NOs: 1-47.


In some embodiments, the compositions disclosed herein comprise two or more bacterial strains. In some embodiments, the compositions described herein 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, or at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47, or more bacterial strains (e.g., purified bacterial strains).


In some embodiments, the bacterial composition comprises purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%. 99.3%. 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with the nucleic acid sequences provided by SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists of purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with the nucleic acid sequences of SEQ ID NOS: 1-47. In some embodiments, the bacterial composition consists essentially of purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%. 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with the nucleic acid sequence of SEQ ID NOs: 1-47.


In some embodiments, the bacterial composition comprises 38 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with any of the nucleic acid sequences provided by SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists of 38 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%. 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with any of the nucleic acid sequences of SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists essentially of 38 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%. 99.7%, 99.8%, 99.9%, or 100%) sequence identity with any of the nucleic acid sequence of SEQ ID NOs: 1-47.


In some embodiments, the bacterial composition comprises 33 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with any of the nucleic acid sequences provided by SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists of 33 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100%) sequence identity with any of the nucleic acid sequences of SEQ ID NOs: 1-47. In some embodiments, the bacterial composition consists essentially of 33 purified bacterial strains comprising 16S rDNA sequences having at least 97% (e.g., 97%, 98%, 99,%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%. 99.7%, 99.8%, 99.9%, or 100%) sequence identity with any of the nucleic acid sequence of SEQ ID NOs: 1-47.


Provided herein are bacterial strains and combinations of bacterial strains that are homologous or have a high percent of homology with bacterial strains comprising 16S rDNA sequences selected from SEQ ID NO: 1-83. It should be appreciated that the bacterial strains described herein have a 16S rDNA sequence selected from SEQ ID NO: 1-83 may also be homologous to other strains based on their whole genome sequence, or subset of their whole genome sequence.


In one aspect, the compositions comprise a fraction of a fecal sample. In some embodiments, the compositions comprise a non-spore forming fraction of a fecal sample. In some embodiments, the compositions comprise a spore forming fraction of a fecal sample.


In some embodiments, the compositions described herein comprise spore forming and non-spore forming bacterial strains. In some embodiments, the compositions described herein comprise spore forming bacterial strains. In some embodiments, the compositions described herein comprise only spore forming bacterial strains. In some embodiments, the compositions described herein comprise only non-spore forming bacterial strains. The spore-forming bacteria can be in spore form (i.e., as spores) or in vegetative form (i.e., as vegetative cells). In spore form, bacteria are generally more resistant to environmental conditions, such as heat, acid, radiation, oxygen, chemicals, and antibiotics. In contrast, in the vegetative state or actively growing state, bacteria are more susceptible to such environmental conditions, compared to in the spore form. In general, bacterial spores are able to germinate from the spore form into a vegetative/actively growing state, under appropriate conditions. For instance, bacteria in spore form may germinate when they are introduced in the intestine.


In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is a spore former. In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is in spore form. In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is a non-spore former. In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is in vegetative form. As discussed above, spore forming bacteria can also be in vegetative form. In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is in spore form and at least one (e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in the composition is in vegetative form. In some embodiments, at least one bacterial strain that is considered able to form spores (i.e., a spore-former) is present in the composition in vegetative form. In some embodiments, at least one bacterial strain that is considered able to form spores is present in the composition both in spore form and in vegetative form.


In some embodiments, the compositions comprise bacterial strains that are spore forming bacterial strains. In some embodiments, the compositions comprise bacterial strains that are non-spore forming bacterial strains. In some embodiments, the compositions comprise bacterial strains that are spore forming bacterial strains and bacterial strains that are non-spore forming bacterial strains. In some embodiments, the compositions comprise a mixture of bacterial strains wherein at least 10% of the bacterial strains are spore forming bacterial strains, at least 20% of the bacterial strains are spore forming bacterial strains, at least 30% of the bacterial strains are spore forming bacterial strains, at least 40% of the bacterial strains are spore forming bacterial strains, at least 50% of the bacterial strains are spore forming bacterial strains, at least 60% of the bacterial strains are spore forming bacterial strains, at least 70% of the bacterial strains are spore forming bacterial strains, at least 80% of the bacterial strains are spore forming bacterial strains, at least 90% of the bacterial strains are spore forming bacterial strains bacteria or up to 100% of the bacterial strains are spore forming bacterial strains. Whether a bacterial strain is a spore forming strain can be determined for instance by evaluating the genome of the bacterial strain for the presence of sporulation genes. However, it should be appreciated that not all bacteria that are predicted to encode spore forming genes can be made to sporulate. In addition, whether a bacterial strain is a spore forming strain can be determined by exposing the bacterial strain to stress conditions, e.g., heat or exposure to chemicals (e.g., ethanol or chloroform), that are known to induce sporulation.


It should be appreciated that spore forming bacteria can be in spore form or in vegetative form. In some embodiments of the compositions provided herein, the spore forming bacteria are in spore form. In some embodiments, the spore forming bacteria are in vegetative form. In some embodiments, the spore forming bacteria are both present in spore form and in vegetative form. In some embodiments, compositions comprise spore forming bacteria and at least 10% of the spore forming bacteria are in spore format, at least 20% of the spore forming bacteria are in spore format, at least 30% of the spore forming bacteria are in spore format, at least 40% of the spore forming bacteria are in spore format, at least 50% of the spore forming bacteria are in spore format, at least 60% of the spore forming bacteria are in spore format, at least 70% of the spore forming bacteria are in spore format, at least 80% of the spore forming bacteria are in spore format, at least 90% of the spore forming bacteria are in spore format, or up to 100% of the spore forming bacteria are in spore format.


It is envisioned that the bacterial strains of the compositions provided herein are alive and will be alive when they reach the target area (e.g., the intestines). Bacterial spores are considered to be alive in this regard. In some embodiments, bacteria that are administered as spores may germinate in the target area (e.g., the intestines). It should further be appreciated that not all of the bacteria are alive, and the compositions can include a percentage (e.g., by weight) that is not alive. In addition, in some embodiments, the compositions include bacterial strains that are not alive when administered or at the time when the composition reaches the target area (e.g., the intestines). It is envisioned that non-living bacteria may still be useful by providing some nutrients and metabolites for the other bacterial strains in the composition.


Methods of inducing sporulation of spore-forming bacterial strains are well-known in the art (see, e.g., Paredes-Sabja et al., Trends Microbiol. (2011) 19(2):85-94). Generally, bacterial strains that are spore-formers can be made to go into spore form by stressing the bacterial strains. Non-limiting examples of stresses that can induce sporulation are an increase in temperature, change in the nutrients available and/or exposure to chemicals (e.g., ethanol or chloroform). It should be noted that bacteria that are non-spore formers, for instance because they are missing sporulation genes, cannot be made to sporulate by stress. To prepare compositions in which all the bacterial strains are in the spore form, the composition or bacterial cultures used to prepare the composition may be subjected to treatment to kill any bacteria not in spore form (e.g., in vegetative form), for example by exposing the composition to heat and chemically breaking down the non-spore bacteria. The bacteria in spore format can subsequently be separated from the non-spore bacteria for instance by filtration.


The amount of spores can be quantified using techniques known in the art. These techniques include phase contrast microscopy for enumerating spores using a hemocytometer. In addition, the viability of spores can be determined by plating the spores and growing the spores. For instance, spores can be plated in appropriate media and incubated in the anaerobic chamber for a period of time (e.g., 48-96 hrs.). Viability can subsequently be determined by quantifying the colony forming units which correspond to spores that germinated. For instance, spores can be plated on TCCFA plates (taurocholate, cycloserine, cefoxintin, fructose agar plates), in which taurocholate helps the spores to germinate. In addition, spores can be quantified using the dipicolinic assay (DPA assay). DPA is an agent that allows for spore selection and is a clear indicator of endospores. When complexed with terbium, bright green luminescence is observed.


In some embodiments, the compositions comprise bacterial strains that are non-spore forming bacterial strains. In some embodiments, the compositions comprise bacterial strains that are spore forming bacterial strains and bacterial strains that are non-spore forming bacterial strains. In some embodiments, the compositions comprise a mixture of bacterial strains wherein at least 10% of the bacterial strains are non-spore forming bacterial strains, at least 20% of the bacterial strains are non-spore forming bacterial strains, at least 30% of the bacterial strains are non-spore forming bacterial strains, at least 40% of the bacterial strains are non-spore forming bacterial strains, at least 50% of the bacterial strains are non-spore forming bacterial strains, at least 60% of the bacterial strains are non-spore forming bacterial strains, at least 70% of the bacterial strains are non-spore forming bacterial strains, at least 80% of the bacterial strains are non-spore forming bacterial strains, at least 90% of the bacterial strains are non-spore forming bacterial strains, or up to 100% non-spore forming bacterial strains.


In any of the compositions provided herein, the bacterial strains may be purified. In any of the compositions provided herein, the bacterial strains may be isolated. Any of the bacterial strains described herein may be isolated and/or purified, for example, from a source such as a culture or a microbiota sample (e.g., fecal matter). The bacterial strains used in the compositions provided herein generally are isolated from the microbiome of healthy individuals. However, bacterial strains can also be isolated from individuals that are considered not to be healthy. In some embodiments, the compositions include strains originating from multiple individuals.


As used herein, the term “isolated” refers to a bacterium or bacterial strain that has been separated from one or more undesired component, such as another bacterium or bacterial strain, one or more component of a growth medium, and/or one or more component of a sample, such as a fecal sample. In some embodiments, the bacteria are substantially isolated from a source such that other components of the source are not detected.


As also used herein, the term “purified” refers to a bacterial strain or composition comprising such that has been separated from one or more components, such as contaminants. In some embodiments, the bacterial strain is substantially free of contaminants. In some embodiments, one or more bacterial strains of a composition may be independently purified from one or more other bacteria produced and/or present in a culture or a sample containing the bacterial strain. In some embodiments, a bacterial strain is isolated or purified from a sample and then cultured under the appropriate conditions for bacterial replication, e.g., under anaerobic culture conditions. The bacteria that is grown under appropriate conditions for bacterial replication can subsequently be isolated/purified from the culture in which it is grown.


In some embodiments, the bacterial strains of the compositions provided herein are obligate anaerobes. In some embodiments, the bacterial strains of the compositions provided.


Aspects of the present disclosure are related to methods for suppressing undesired bacteria. As used herein, the term “suppressing” refers to any form of inhibiting undesired bacteria. In some embodiments, the methods described herein reduce/inhibit or prevent the colonization, replication, proliferation, and/or survival of the undesired bacteria (e.g., pathogenic organisms, multi-drug resistant organisms, for example carbapenem resistanct Enterobacteriaceae (CRE) and extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae). In some embodiments, the methods described herein directly or indirectly induce death of the undesired bacteria (e.g., pathogenic organism, multi-drug resistant organisms, for example carbapenem resistanct Enterobacteriaceae (CRE) and extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae).


Aspects of the present disclosure are related to methods for suppressing infection by a pathogenic organism in a subject. Aspects of the present disclosure are related to methods for reducing or preventing colonization by a pathogenic organism (e.g., bacterium, virus, fungus, or parasite) in a subject. Aspects of the present disclosure are related to methods for treating infection with a pathogenic organism. In some embodiments, the pathogenic organism is not multi-drug resistant. In some embodiments, the pathogenic organism resistant to one or more drugs (e.g., antibacterial, anti-viral, anti-fungal agent). In some embodiments, the pathogenic organism is multi-drug resistant. The methods described herein involve administering to a subject a therapeutically effective amount of any of the compositions described herein. As used herein, a “subject,” “individual,” and “patient” are used interchangeably, and refer to a vertebrate, preferably a mammal such as a human. Mammals include, but are not limited to, human primates, non-human primates or murine, bovine, equine, canine or feline species. In some embodiments, the subject is a human.


In some embodiments, any of the compositions described herein are effective in suppressing the replication, survival, and/or colonization of one or more pathogenic organism. In some instances, the pathogenic organism is susceptible to antibiotics, while in other instances, the pathogenic organism is resistant to antibiotics. In some embodiments, the pathogenic organism is a multi-drug resistant organism, which are described elsewhere herein. In some embodiments, the pathogenic organism is an oral microbiome bacterium. It should be noted that oral microbiome bacteria are not necessarily pathogenic, but may become so when located elsewhere, such as in the gastrointestinal tract. The amount of suppression of replication, survival, and/or colonization of the one or more pathogenic organism can be measured or identified using standard assays known in the art, some of which are further described and exemplified herein.


In some embodiments, administration of the compositions described herein reduces/inhibits or prevents the colonization, re-colonization, replication, proliferation, and/or survival of pathogenic organism, such as multi-drug resistant organisms. In some embodiments, administration of the compositions described herein allows for colonization of the gastrointestinal tract of the subject by the bacterial strain(s) of the compositions thereby preventing colonization by multi-drug resistant organisms.


In some embodiments, the pathogenic organism is a pathobiont, i.e., a potentially pathogenic organism which, under normal circumstances, lives as a symbiont.


In some embodiments, the subject is a carrier of a multi-drug resistant organism and is suffering from the effects of the infection. In some embodiments the subject is an asymptomatic carrier of a multi-drug resistant organism. In some embodiments, the subject has experienced recurrent or chronic colonization with a multi-drug resistant organism. In some embodiments, the subject is suffering from a first occurrence of a particular multi-drug resistant organism. In some embodiments, the subject is at risk of colonization with a multi-drug resistant organism, such as prior antibiotic use. In some embodiments, the subject has a risk factor associated with colonization with a multidrug resistant organism. In some embodiments, the subject has had a previous infection or colonization with a multi-drug resistant organism. In some embodiments, the subject has been treated with antibiotics which resulted in the recurrence of the multi-drug resistant organism.


In some embodiments, the subject is to undergo a procedure that puts the subject at a higher risk of colonization and the compositions are administered prophylactically. In some embodiments, the subject has a disease or disorder associated with use of a proton pump inhibitor, which may increase the likelihood of an oral bacterium migrating to the intestine. In some embodiments, the compositions provided herein are administered to a subject to lower the risk of becoming colonized with a multidrug resistant organism. In some embodiments, the bacterial compositions provided herein administered to a subject that is receiving a proton pump inhibitor.


Individuals may be at risk of acquiring a multi-drug resistant organism if they have recently received antimicrobials, are in an immunosuppressed state (e.g., on chemotherapy, have a malignancy, undergoing or received a transplant), have a chronic disease or inflammatory condition (such as diabetes, renal disease, etc.), are older, are undergoing hemodialysis, surgery or other invasive procedures, have indwelling device(s), and/or are living in a long-term care facility or are hospitalized. In some embodiments, the subject is colonized with a multi-drug resistant organism. Skin and mucosal colonization are common (Cassone et al., Curr Geriatr Rep. (2015) 4(1): 87-89), but multi-drug resistant organisms may also colonize the gastrointestinal (GI) tract and oral cavity, causing inflammation (Atarashi et al., Science (2017) 358, 359-365). Colonization can lead to significant infections, such as in the skin, lungs, urinary tract, or bloodstream, which may result in serious complications, including death (CDC, 2013). In some instances, multi-drug resistant organisms may be ingested, leading to consequences throughout the digestive system. In some embodiments, a multi-drug resistant organism may colonize the oral cavity.


In some embodiments, the multi-drug resistant organism is Vancomycin Resistant Enterococci (VRE), Carbapenem Resistant Enterobacteriaceae (CRE), Neisseria gonorrheae, Multidrug Resistant Acinetobacter, Campylobacter, Extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, ESBL-producing Escherichia coli, Multidrug Resistant Pseudomonas aeruginosa, Salmonella, Drug resistant non-typhoid Salmonella, Drug resistant Salmonella Typhi, Drug resistant Shigella, Methicillin Resistant Staphylococcus aureus, Drug resistant Streptococcus pneumoniae, Drug resistant Tuberculosis, Vancomycin resistant Staphylococcus aureus, Erythromycin Resistant Group A Streptococcus, or Clindamycin resistant Group B Streptococcus. In some embodiments, the multi-drug resistant organism is Vancomycin Resistant Enterococci (VRE). In some embodiments, the multi-drug resistant organism is Carbapenem Resistant Enterobacteriaceae (CRE).


In some embodiments, the compositions described herein are effective in reducing or preventing colonization by more than one multi-drug resistant organism. In some embodiments, the compositions described herein are effective in treating infection of more than one multi-drug resistant organism. For example, in some embodiments, the compositions described herein are effective in reducing or preventing, or treating infection, with a carbapenem resistant Enterobacteriaceae (CRE) and Extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae,


Enterobacteriaceae is a broad family of bacteria that includes a number of bacterial pathogens. Bacteria belonging to the Enterobacteriaceae family are characterized as being Gram negative and are frequently found in the gut flora of the intestinal tract of humans and mammals but may also be found in water and soil. Non-limiting examples of bacterial genera belonging to the Enterobacteriaceae family include Alishewanella, Buttiauxella, Grimontella, Pectobacterium, Salmonella, Yokenella, Alterococcus, Cedecea, Hafnia, Phlomobacter, Samsonia, Aquamonas, Citrobacter, Klebsiella, Photorhabdus, Serratia, Aranicola, Cronobacter, Kluyvera, Poodoomaamaana, Shigella, Arsenophonus, Dickeya, Leclercia, Plesiomonas, Sodalis, Azotivirga, Edwardsiella, Leminorella, Pragia, Tatumella, Blochmannia, Enterobacter, Moellerella, Proteus, Trabulsiella, Brenneria, Erwinia, Morganella, Providencia, Wigglesworthia, Buchnera, Escherichia, Obesumbacterium Rahnella, Xenorhabdus, Budvicia, Ewingella, Pantoea, Raoultella, and Yersinia.


In some embodiments, the compositions described herein are effective in reducing or preventing, or treating infection, with a carbapenem resistant Enterobacteriaceae (CRE). As used herein, the terms “carbapenem resistant Enterobacteriaceae” or “CRE” refer to a bacterial strain or species that belongs to the Enterobacteriaceae family and has developed resistance to carbapenem antibiotics. In some embodiments, the CRE is also resistant to additional antibiotics in addition to carbapenem antibiotics.


In some embodiments, the Carbapenem Resistant Enterobacteriaceae is carbapenem-resistant Klebsiella pneumoniae. Examples of CRE Klebsiella pneumoniae is Klebsiella pneumoniae strain ATCC 700721.


In some embodiments, the compositions described herein are effective in reducing or preventing, or treating infection, with an extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. As used herein, the terms “extended spectrum beta-lactamase Enterobacteriaceae” or “ESBL-Enterobacteriaceae” refer to a bacterial strain or species that belongs to the Enterobacteriaceae family and produce or are capable of producing beta-lactamase enzymes that breakdown or inactivate antibiotics. In some embodiments, the ESBL Enterobacteriaceae is resistant to one or more antibiotics (e.g., beta-lactam antibiotics).


In some embodiments, the ESBL Enterobacteriaceae is also resistant to additional antibiotics in addition to beta-lactam antibiotics.


In some embodiments, the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae or ESBL-producing E. coli. In some embodiments, the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae subsp. pneumoniae (ATCC 700721), ESBL-producing E. coli ATCC BAA 2777 adherent/invasive E. coli (AIEC), Shiga toxin-producing E. coli (STEC), Verocytotoxin-producing E. coli (VTEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), or diffusely adherent E. coli (DAEC).


In some embodiments, the CRE or ESBL-producing Enterobacteriaceae is Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae, Enterobacter aerogenes, Enterobacter sakasakii, Escherichia coli, Escherichia albertii, Proteus mirabilis, Proteus vulgaris, Salmonella enterica, Serratia marcescens, Shigella dysenterii, Shigella flexneri, Shigella sonnei, Shigella boydii, Yersinia pestis, Yersinia enterocolitica, or Yersinia pseudotuberculosis.


Aspects of the present disclosure are related to methods for suppressing pathogenic organisms in a subject. In some embodiments, the pathogenic organism is susceptible to antibiotics (e.g., not a multi-drug resistant organism). Pathogenic organisms are organisms that are capable of causing disease in a subject and may be viruses, bacteria, fungi, protozoa, and worms. Non-limiting examples of pathogenic organisms of the present disclosure include Salmonella, Shigella, Staphylococcus, Streptococcus, Enterococcus, Enterobacteriaceae, Neisseria gonorrheae, Acinetobacter, Campylobacter, Clostridium, Listeria, Escherichia, Pseudomonas aeruginosa, Salmonella, Shigella, Staphylococcus aureus, Streptococcus pneumoniae, Tuberculosis, Group A Streptococcus, or Group B Streptococcus, Toxoplasma, Cyclospora, Giardia, Cryptosporidium, and Trichinella.


In some embodiments, pathogenic organisms in the subject are resistant to treatment with a drug. In some embodiments, pathogenic organisms in the subject are resistant to treatment with multiple drugs (e.g., multi-drug resistant). Drugs that may be used to treat pathogenic organisms of the present disclosure may include antibiotics, antivirals, antifungals, and antiparasitics.


In some embodiments, a pathogenic organism that is susceptible to a drug may acquire resistance to one or more drugs. In some embodiments, a pathogenic organism that is susceptible to antibiotics may acquire resistance to one or more antibiotics. In some embodiments, a pathogenic organism is resistant to one or more drugs (e.g., antibiotics) and may acquire resistance to one or more drugs (e.g., antibiotics). In some embodiments, the pathogenic organism is resistant to one or more drugs (e.g., antibiotics) and may become a multi-drug resistant organism by acquiring resistance to more than one drugs (e.g., antibiotics).


In general, there are multiple means by which an organism may acquire drug resistance. In some embodiments, the organism may acquire drug resistance by acquiring mutations in its genome that promote survival of the organism in the presence of at least one drug. In some embodiments, the organism acquires DNA from an organism that is resistant to one or more drugs (e.g., antibiotics), thereby becoming resistant to the drug (e.g., antibiotic). In some embodiments, the organism acquires a plasmid, such as a plasmid containing one or more drug (e.g., antibiotic) resistance genes, from an organism that is resistant to one or more drugs (e.g., antibiotics), thereby becoming resistant to the drug (e.g., antibiotic).


In some embodiments, administration of the compositions described herein reduces/inhibits or prevents intestinal colonization with oral microbiome bacteria. In some embodiments, administration of the compositions described herein reduces/inhibits or prevents the colonization, replication, proliferation, and/or survival of oral microbiome bacteria in the intestinal tract of the subject. In some embodiments, administration of the compositions described herein allows for colonization of the gastrointestinal tract of the subject by the bacterial strain(s) of the compositions thereby preventing colonization by oral microbiome bacteria.


In some embodiments, the subject is a carrier of an oral bacterium and is suffering from the effects of the infection. In some embodiments the subject is an asymptomatic carrier of an oral bacterium. In some embodiments, the subject has experienced recurrent or chronic colonization with an oral bacterium. In some embodiments, the subject is at risk of colonization with an oral bacterium. In some embodiments, the subject has a risk factor associated with colonization with an oral bacterium. In some embodiments, the subject is taking a proton pump inhibitor. In some embodiments, the subject has had a previous infection or colonization with an oral bacterium.


In some embodiments, the subject is to undergo a procedure that puts the subject at a higher risk of colonization and the compositions are administered prophylactically. In some embodiments, the compositions provided herein are administered to a subject to lower the risk of becoming colonized with an oral bacterium.


Over 700 bacterial species or phylotypes have been found in the oral cavity; however, over 50% have not yet been cultivated. A number of phyla have been identified in the oral microbiome Actinobacteria, Arachnia, Bacteroidetes, Bifidobacterium, Chlamydiae, Chloroflexi, Eubacterium, Euryarchaeota, Fusobacterium, Firmicutes, Fusobacteria, Lactobacillus, Leptotrichia, Peptococcus, Peptostreptococcus, Propionibacterium, Proteobacteria, Selenomonas, Spirochaetes, SRI, Synergistetes, Tenericutes, Treponema, TM7, and Veillonella (Dewhirst et al., J. Bacteriology (2010) 192(19): 5002-5010). Examples of oral microbiome bacteria include, without limitation, Streptococcus sanguis, Streptococcus salivarius, Streptococcus mitis, Streptococcus mutans, Treponema denticola, Eikenella corrodens, Streptococcus gordonii, Streptococcus oralis, Acinomyces maeslundii, and Bacteroides melaningenicus. A list of example species found in the human oral cavity can be found on the Human Oral Microbiome Database (homd.org). In some embodiments, the oral microbiome bacteria may be pathogenic. In some embodiments, the oral microbiome bacteria may be pathogenic if the bacteria gain access to another site of the body. In some embodiments, the oral microbiome bacteria are not pathogenic.


In some embodiments, administration of the compositions described herein reduces/inhibits or prevents intestinal colonization with oral microbiome bacteria. In some embodiments, the oral microbiome bacteria are Fusobacterium nucleatum (See e.g., Yoneda et al. J Gastrointest Dig Syst (2016) 6:2). In some embodiments, the oral microbiome bacteria are Campylobacter concisus (See e.g., Yoneda et al. J Gastrointest Dig Syst (2016) 6:2). In some embodiments, the oral microbiome bacteria are Streptococcus mutans (See e.g., Yoneda et al. J Gastrointest Dig Syst (2016) 6:2). Additional oral microbiome bacteria are described in Table S1A of Atarashi et al. (Atarashi et al., Science (2017) 358, 359-365), such as Rothia mucilaginosa, Neisseria subflava, Granulicatella para-adiacens, Streptococcus salivarius, Streptococcus mitis, Fusobacterium sp. 1_1_41FAA, Streptococcus oralis, Streptococcus salivarius, Neisseria subflava, Prevotella scopos, Veillonella parvula, Streptococcus sp. M143, Haemophilus parainfluenzae, Prevotella sp. CD3_34, Neisseria macacae, Prevotella histicola, Prevotella pallens, Streptococcus infantis, Streptococcus parasanguinis, Porphyromonas CW034, Streptococcus sp. oral strain T1-E5, Gemella sp. 933-88, Veillonella parvula, and Prevotella sp. C561.


In some embodiments, intestinal colonization with an oral microbiome bacterium induces a Th1 immune response in the subject. Examples of oral microbiome bacteria that may induce Th1 immune responses have been isolated, showing significant similarity (>96.3%) to the following species: Mogibacterium sp. CM96, Peptostreptococcus stomatis, Bifidobacterium sp. Group III-3, Slackia exigua, Veillonella denticariosi, Atopobium parvulum, Veillonella sp. 2011_oral_VSA_A3, Campylobacter concisus, Actinomyces odontolyticus, Solobacterium moorei, Enterococcus faecium, Bifidobacterium dentium, Veillonella parvela, Fusobacterium sp. 3_1_33, Klebsiella aeromobilis, and Klebsiella pneumoniae (see, e.g., Atarashi et al., Science (2017) 358: 359-365, Schirmer et al., Cell Host and Microbe (2018) 24: 600-610).


In some embodiments, the bacterium that induces a Th1 immune response (e.g., IBD) in a subject is a pathobiont. “Pathobiont” refers to a potentially pathological (disease-causing) organism which, under normal circumstances, lives as a symbiont. Examples of pathobionts include a bacterium that is associated with chronic inflammatory conditions (e.g., IBD). Non-limiting examples of pathobionts include Shigella spp., Campylobacter spp., Cryptosporidium spp., Salmonella spp., Escherichia coli strains (e.g., Enteropathogenic E. coli, Enteroaggregative E. coli, Enterotoxigenic E. coli), Veillonella dispar, Aggregatibacter segnis, Campylobacter, Lachnospiraceae, Veillonella parvula, Haemophilus parainfluenzae, Megasphaera, Escherichia coli, Enterobacteriaceae spp., Enterococcus spp., Fusobacterium spp., Gemella spp., Veillonella spp., Pasteurella spp., Neisseria spp., Haemophilus spp., Campylobacter spp., and Bifidobacterium spp.


In some embodiments, the methods may involve determining whether an oral bacterium is present in the subject. In some embodiments, the methods may involve determining whether an oral bacterium colonizes the oral cavity of the subject. In some embodiments, a subject may be at risk of intestinal colonization if the oral bacterium is present in the oral cavity of the subject. In some embodiments, the methods involve administering the combinations described herein to the subject, if an oral bacterium is detected in the oral cavity of the subject.


In some embodiments, the methods may involve determining whether an oral bacterium is present in the intestine of the subject. In some embodiments, the methods involve administering the combinations described herein to the subject, if an oral bacterium is detected in the intestine of the subject.


In some embodiments, the methods are for treating a disease or disorder associated with bacterial colonization in a subject. In some embodiments, the methods are for treating a disease or disorder associated with an immune response induced by bacteria in a subject. In some embodiments, the methods are for treating a disease or disorder associated with an undesired immune response induced by bacteria in a subject.


In some embodiments, the methods may involve determining whether the subject is colonized with bacteria. In some embodiments, the methods may involve determining whether the subject has or is experiencing an immune response induced by bacterial colonization. In some embodiments, a subject may be at risk of an immune response induced by bacterial colonization if the subject is colonized by the bacteria. In some embodiments, the methods involve administering the combinations described herein to the subject, if the subject is determined to be colonized by the bacteria. In some embodiments, the methods involve administering the combinations described herein to the subject, if the subject is determined to be experiencing or have experienced an immune response induced by bacterial colonization.


In some embodiments, the immune response induced by bacterial colonization is a Th1 immune response. As will be evident to one of skill in the art, Th1 immune responses are mediated the Th1 population of CD4+ cells. Th1 cells produce IFN-γ and other pro-inflammatory factors. The differentiation of CD4+ cells to Th1 cells is promoted by the presence of IL-2 and/or IL-12 and activation of the transcription factors STAT4 and T-bet. In some embodiments, the immune responses induced by bacterial colonization are Th1 pro-inflammatory responses. Any direct or indirect measure of Th1 immune response, such as the amount of IFN-γ or the number of Th1 cells, may be used to assess the level or extent of the immune response in a sample from a subject.


In some embodiments, the compositions provided herein are administered to a subject if the subject has an autoimmune disease. Examples of autoimmune diseases include, without limitation, inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, sprue, autoimmune arthritis, rheumatoid arthritis, graft versus host disease, Type I diabetes, multiple sclerosis, osteoarthritis, juvenile chronic arthritis, Lyme arthritis, psoriatic arthritis, reactive arthritis, spondyloarthropathy, systemic lupus erythematosus, insulin dependent diabetes mellitus, thyroiditis, asthma, psoriasis, dermatitis scleroderma, atopic dermatitis, sarcoidosis, atherosclerosis, disseminated intravascular coagulation, Kawasaki's disease, Grave's disease, nephrotic syndrome, chronic fatigue syndrome, Wegener's granulomatosis, Henoch-Schoenlejn purpurea, microscopic vasculitis of the kidneys, chronic active hepatitis, uveitis, cachexia, acute transverse myelitis, Huntington's chorea, Parkinson's disease, Alzheimer's disease, stroke, primary biliary cirrhosis, hemolytic anemia, polyglandular deficiency type I syndrome and polyglandular deficiency type II syndrome, Schmidt's syndrome, adult (acute) respiratory distress syndrome, alopecia, alopecia areata, seronegative arthopathy, arthropathy, Reiter's disease, psoriatic arthropathy, chlamydia, yersinia and salmonella associated arthropathy, spondyloarhopathy, atheromatous disease/arteriosclerosis, pemphigus vulgaris, pemphigus foliaceus, pemphigoid, linear IgA disease, autoimmune haemolytic anaemia, Coombs positive haemolytic anaemia, acquired pernicious anaemia, juvenile pernicious anaemia, myalgic encephalitis/Royal Free Disease, chronic mucocutaneous candidiasis, giant cell arteritis, primary sclerosing hepatitis, cryptogenic autoimmune hepatitis, Acquired Immunodeficiency Disease Syndrome, Acquired Immunodeficiency Related Diseases, common varied immunodeficiency (common variable hypogammaglobulinaemia), dilated cardiomyopathy, fibrotic lung disease, cryptogenic fibrosing alveolitis, postinflammatory interstitial lung disease, interstitial pneumonitis, connective tissue disease associated interstitial lung disease, mixed connective tissue disease associated lung disease, systemic sclerosis associated interstitial lung disease, rheumatoid arthritis associated interstitial lung disease, systemic lupus erythematosus associated lung disease, dermatomyositis/polymyositis associated lung disease, Sjogren's disease associated lung disease, ankylosing spondylitis associated lung disease, vasculitic diffuse lung disease, haemosiderosis associated lung disease, drug-induced interstitial lung disease, radiation fibrosis, bronchiolitis obliterans, chronic cosinophilic pneumonia, lymphocytic infiltrative lung disease, postinfectious interstitial lung disease, gouty arthritis, autoimmune hepatitis, type-1 autoimmune hepatitis (classical autoimmune or lupoid hepatitis), autoimmune mediated hypoglycemia, type B insulin resistance with acanthosis nigricans, hypoparathyroidism, acute immune disease associated with organ transplantation, chronic immune disease associated with organ transplantation, osteoarthrosis, primary sclerosing cholangitis, idiopathic leucopenia, autoimmune neutropenia, renal disease NOS, glomerulonephritides, microscopic vasulitis of the kidneys, discoid lupus, erythematosus, male infertility idiopathic or NOS, sperm autoimmunity, insulin-dependent diabetes mellitus, sympathetic ophthalmia, pulmonary hypertension secondary to connective tissue disease, Goodpasture's syndrome, pulmonary manifestation of polyarteritis nodosa, acute rheumatic fever, rheumatoid spondylitis, Still's disease, systemic sclerosis, Takayasu's disease/arteritis, autoimmune thrombocytopenia, idiopathic thrombocytopenia, autoimmune thyroid disease, hyperthyroidism, goitrous autoimmune hypothyroidism (Hashimoto's disease), atrophic autoimmune hypothyroidism, primary myxoedema, phacogenic uveitis, primary vasculitis, vitiligo, cosinophilic esophagitis, hypereosinophilic syndrome, eosinophilic gastroenteritis cutaneous lupus erythematosus, eosinophilic esophagitis, hypereosinophilic syndrome, and cosinophilic gastroenteritis, and diarrhea. In some embodiments, the autoimmune disease is inflammatory bowel disease (IBD). In some embodiments, the autoimmune disease is ulcerative colitis. In some embodiments, the autoimmune disease is Crohn's disease.


In some embodiments, the compositions provided herein are administered to a subject if the subject has non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), non-alcoholic fatty liver disease (NAFLD), gastroesophageal reflux disease (GERD), or alcoholism.


In some embodiments, the compositions provided herein are administered to a subject if an immune response associated with bacterial colonization has been detected in the subject. In some embodiments, the methods involve determining whether the subject has an immune response induced by or associated with colonization with an undesired organism.


In some embodiments, the compositions provided herein are administered to a subject if the subject has a dysbiosis (e.g., has as microbiome associated with a disease state). In some embodiments, treatment with the compositions provided herein results in the change in the microbiome of the subject. In some embodiments, treatment with the compositions provided herein removes the dysbiosis in the subject resulting in a healthy microbiome. In some embodiments, treatment with the compositions provided herein removes the dysbiosis in the subject resulting in microbiome refractory or less susceptible to infection by a pathogen.


In some embodiments, the compositions and methods described herein are for the treatment and/or prevention of sepsis. In some embodiments, the compositions provided herein are administered to a subject if the subject has or is at risk for sepsis. In some embodiments, the compositions and methods described herein are for the treatment and/or prevention of sepsis in critically ill subjects, such as patients in an intensive care unit (ICU, also referred to as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU)). In some embodiments, the compositions provided herein are administered to a subject if the subject is a critically ill subject and has or is at risk for sepsis. As will be evident to one of ordinary skill in the art, sepsis is a systemic inflammatory response that is typically due to infection with bacterium, fungus, virus, or protozoa. The severity of sepsis can range from mild (sepsis) to severe sepsis or even septic shock. Subjects of advanced age (e.g., over 65 years old), young age (e.g., under 1 year old), and/or having a compromised immune systems, including due to cancer, diabetes, burns, trauma, or other disease or disorder resulting in a critical illness, may be at increased risk of developing sepsis.


In some embodiments, the compositions and methods described herein are for the treatment and/or prevention of infection in critically ill subjects, such as patients in an intensive care unit (ICU). In some embodiments, the compositions provided herein are administered to a subject if the subject is a critically ill subject. In some embodiments, the subject may be a patient in an intensive care unit. In some embodiments, any of the compositions described herein may be administered to a subject to treat and/or prevent a bacterial infection, fungal infection, viral infection, or protozoan infection in a critically ill subject.


In some embodiments, the compositions and methods described herein are for the treatment and/or prevention of infection following a surgical procedure involving the gastrointestinal tract (i.e., gastrointestinal surgery). In some embodiments, the compositions and methods described herein are administered to a subject if the subject has undergone a surgical procedure involving the gastrointestinal tract. In some embodiments, the compositions and methods described herein are administered to a subject if the subject will be undergoing a surgical procedure involving the gastrointestinal tract (e.g., administered prior to the surgical procedure). In some embodiments, the subject has a disease or disorder associated with the gastrointestinal tract. In some embodiments, any of the compositions described herein may be administered to a subject to treat and/or prevent a bacterial infection, fungal infection, viral infection, or protozoan infection.


In some embodiments, the compositions and methods described herein are for the treatment and/or prevention of infection in subjects having cirrhosis (i.e., a cirrhosis patient). In some embodiments, the compositions and methods described herein are administered to a subject if the subject has or is at risk of cirrhosis. As will be evident to one of ordinary skill in the art, cirrhosis, also referred to as liver cirrhosis or hepatic cirrhosis, is a condition associated with liver dysfunction, predominantly due to long-term damage of the liver tissue and cells thereof. Cirrhosis may be caused by any of a variety of factors, for example, hepatitis (e.g., viral infection with Hepatitis B or Hepatitis C, autoimmune hepatitis), and excessive alcohol consumption. In some embodiments, any of the compositions described herein may be administered to a subject to treat and/or prevent a bacterial infection, fungal infection, viral infection, or protozoan infection in a cirrhosis patient.


In some embodiments, the compositions and methods described herein are for the treatment and/or prevention of infection in subjects who received a bone marrow transplant (i.e., bone marrow transplant patients). In some embodiments, the compositions and methods described herein are administered to a subject if the subject has undergone or will undergo a bone marrow transplant. In some embodiments, any of the compositions described herein may be administered to a subject to treat and/or prevent a bacterial infection, fungal infection, viral infection, or protozoan infection in a bone marrow transplant patient.


Any of the compositions described herein may be administered to a subject in a therapeutically effective amount or a dose of a therapeutically effective amount to treat or prevent a disease or disorder, for example associated with colonization with bacteria or an immune response associated with colonization with bacteria. The terms “treat” and “treatment” refer to reducing or alleviating one or more of the symptoms associated with colonization with bacteria or an immune response associated with colonization with bacteria. In some embodiments, any of the compositions described herein may be administered to a subject to prevent a disease or disorder. In some embodiments, any of the compositions described herein may be administered to a subject to prevent a Th1 related disease or disorder. In some embodiments, any of the compositions described herein may be administered to a subject to prevent IBD. The terms “prevent” and “prevention” encompass prophylactic administration and may reduce the incidence or likelihood of colonization with bacteria or an immune response associated with colonization with bacteria. For instance, in some embodiments, administration of the compositions provided herein result in a healthy microbiome that is refractory to pathogenic infection, thereby preventing the pathogenic infection or re-colonization with the pathogenic organism.


As used herein, a “therapeutically effective amount” may be used interchangeably with the term “effective amount.” A therapeutically effective amount or an effective amount of composition, such as a pharmaceutical composition, is any amount that results in a desired response or outcome in a subject, such as those described herein, including but not limited to reducing or preventing colonization with bacteria or an immune response associated with colonization with bacteria.


It should be appreciated that the term effective amount may be expressed as the number of bacteria or bacterial spores to be administered. It should further be appreciated that the bacteria can multiply once administered. Thus, administration of even a relatively small amount of bacteria may have therapeutic effects.


In some embodiments, the therapeutically effective amount of any of the compositions described herein is an amount sufficient to enhance survival of the subject, reduce or prevent bacterial colonization of the subject, and/or reduce or inhibit toxin production by the pathogenic infection. In some embodiments, colonization may be assessed by detecting and/or quantifying the bacteria in a sample from the subject, such as a fecal sample. In some embodiments, the therapeutically effective amount is an amount sufficient to reduce the colonization bacteria (e.g., pathogenic organisms, multi-drug resistant organisms, for example carbapenem resistant Enterobacteriaceae or extended spectrum beta-lactamase producing Enterobacteriaceae) in a fecal sample from the subject by at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, 1000-fold, 104-fold, 105-fold or more, as compared to the bacterial burden in a subject that has not received any of the compositions described herein, or as compared to a fecal sample from the same subject that was collected prior to administration of any of the compositions.


In some embodiments, the compositions provided herein reduce an immune response associated with bacterial colonization or induced by bacterial colonization. In some embodiments, the therapeutically effective amount is an amount sufficient to reduce an immune response associated with bacterial colonization or induced by bacterial colonization by at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, 150-fold, 200-fold, 500-fold or more, as compared to the immune response associated with bacterial colonization or induced by bacterial colonization prior to administration of any of the compositions.


In some embodiments, the therapeutically effective amount is an amount sufficient to recolonize or repopulate the gastrointestinal tract of the subject with non-pathogenic bacteria. In some embodiments, the therapeutically effective amount is an amount sufficient to graft one or more of the bacterial strains of the composition in the gastrointestinal tract of the subject. In some embodiments, a fecal sample is obtained from the subject to assess the bacterial burden of undesired bacteria (e.g., pathogenic organisms, multi-drug resistant organisms, for example carbapenem resistant Enterobacteriaceae or extended spectrum beta-lactamase producing Enterobacteriaceae) and/or evaluate the efficacy of administration of the bacterial compositions described herein. In some embodiments, the microbiota of the subject (e.g., the identity and abundance of strains and/or species of the microbiota) may be assessed to determine a disease state of the subject and/or assess progress of the treatment. In some embodiments, the microbiota of the subject having a pathogenic infection is compared to the microbiota of a healthy subject, such as a subject that is not experiencing or has not experienced the pathogenic infection. In some embodiments, the microbiota of the subject having a pathogenic infection is compared to the microbiota of the same subject from a fecal sample obtained from the subject prior to the pathogenic infection.


In some embodiments, administration of the compositions provided herein results in a healthy microbiome that reduces or prevents colonization of the subject by any undesired organism. In some embodiments, administration of the compositions provided herein results in a healthy microbiome that reduces or prevents intestinal colonization of the subject by any undesired organism (e.g., pathogenic organisms, multi-drug resistant organisms, for example carbapenem resistant Enterobacteriaceae or extended spectrum beta-lactamase producing Enterobacteriaceae). In some embodiments, administration of the compositions provided herein results in a healthy microbiome that reduces an immune response associated with bacterial colonization, such as colonization with undesired bacteria. In some embodiments, administration of the compositions provided herein results in a healthy microbiome that reduces a Th1 immune response in the subject.


Any of the compositions described herein may be administered in combination with one or more additional compositions that can suppress a Th1 response and/or induces the accumulation and/or proliferation of regulatory T cells, and/or Th17 cells. In some embodiments, any of the compositions described herein may be administered in combination with a composition that induces the proliferation and/or accumulation of regulatory T cells (“Treg”).


In some embodiments, any of the compositions described herein may be administered in combination with a Treg inducing composition of bacterial strains, described for instance in Atarashi et al., Nature (2013) 500: 232-236. In some embodiments, the Treg inducing composition comprises at least 5, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, or at least 17 of the following species: Clostridium saccharogumia, Flavonifractor plautii, Clostridium hathewayi, Blautia coccoides, Clostridium bolteae ATCC BAA-613, cf. Clostridium sp. MLG055, Clostridium indolis, Anaerotruncus colihominis, Ruminococcus sp. ID8, Clostridium asparagiforme DSM 15981, Clostridium symbiosum, Clostridium ramosum, Eubacterium contortum, Lachnospiraceae bacterium 5_1_57FAA, Lachnospiraceae bacterium 3_1_57FAA_CT1, Clostridiales bacterium 1_7_47FAA, and Lachnospiraceae bacterium A4. It should be appreciated that subsets of the bacterial compositions described above can also induce Treg cells. Examples of subsets bacteria that induce Treg cells are found for instance in Atarashi et al., Nature (2013) 500: 232-236 and corresponding Supplemental Information. In some embodiments, any of the compositions described herein may be administered in combination with any of the bacterial compositions as described in PCT Publication WO 2016/209806.


In some embodiments, any of the compositions described herein may be administered in combination with any of the bacterial compositions described in PCT Publication WO 2019/094837, which is incorporated herein by reference in its entirety. In some embodiments, any of the compositions described herein may be administered in combination with any of the bacterial compositions described in PCT Publication WO 2019/118515, which is incorporated herein by reference in its entirety. In some embodiments, any of the compositions described herein are administered in combination with a composition of 36 bacterial strains (e.g., the 36-mix, shown in FIG. 2).


As used herein, the phrase “induces proliferation and/or accumulation of regulatory T cells” refers to an effect of inducing the differentiation of immature T cells into regulatory T cells, which differentiation leads to the proliferation and/or the accumulation of regulatory T cells. Further, the meaning of “induces proliferation and/or accumulation of regulatory T cells” includes in vivo effects, in vitro effects, and/or ex vivo effects. In some embodiments, the proliferation and/or accumulation of regulatory T cells may be assessed by detecting and/or quantifying the number of cells that express markers of regulatory T cells (e.g., Foxp3 and CD4), for example by flow cytometry. In some embodiments, the proliferation and/or accumulation of regulatory T cells may be assessed by determining the activity of the regulatory T cells, such as the production of cytokines (e.g., IL-10).


In some embodiments, any of the compositions described herein may be administered in combination with a composition that induces the accumulation and/or proliferation of Th17 cells, see e.g., compositions disclosed in PCT Publication WO 2015/156419, which is incorporated herein by reference in its entirety.


In some embodiments, suppressing live bacterial product also repopulates the microbiota of the subject.


In some embodiments, administration of the compositions described herein results in an increase in the proliferation and/or accumulation of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by at least 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, 1000-fold, 104-fold, 105-fold or more, as compared to the quantity of regulatory T cells in the subject (or particular site in the subject) prior to administration of the compositions. In some embodiments, administration of the compositions described herein results in an increase the proliferation and/or accumulation of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, 1000-fold, 104-fold, 105-fold or more, as compared to the quantity of regulatory T cells in another subject (e.g., a reference subject) who did not receive the compositions.


In some embodiments, administration of the compositions described herein results in an increase the proliferation and/or accumulation of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by at least 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%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150% or more, as compared to the quantity of regulatory T cells in the subject (or particular site in the subject) prior to administration of the compositions. In some embodiments, administration of the compositions described herein results in an increase the proliferation and/or accumulation of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by at least 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%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150% or more, as compared to the quantity of regulatory T cells in another subject (e.g., a reference subject) who did not receive the compositions.


The induction of Treg cells and corresponding decolonization of pathogenic organisms are intricately related. In some embodiments, administration of the compositions described herein results in an increase the proliferation and/or accumulation of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by between 1% and 20%, 2% and 19%, 3% and 17%, 4% and 16%, 4% and 15%, 5% and 15%, 6% and 14%, 7% and 13%, 8% and 12%, 5% and 10%, 5% and 15%, 10% and 15%, or 8% and 15% as compared to the quantity of regulatory T cells in the subject (or particular site in the subject) prior to administration of the compositions. In some embodiments, administration of the compositions described herein results in an increase the proliferation and/or accumulation of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by between 1% and 20%, 2% and 19%, 3% and 17%, 4% and 16%, 4% and 15%, 5% and 15%, 6% and 14%, 7% and 13%, 8% and 12%, 5% and 10%, 5% and 15%, 10% and 15%, or 8% and 15% as compared to the quantity of regulatory T cells in another subject (e.g., a reference subject) who did not receive the compositions.


In some embodiments, administration of the compositions described herein results in an increase in activity of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) at a particular site (e.g., the gastrointestinal tract) in the subject. In some embodiments, administration of the compositions described herein results in an increase in activity of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by at least 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, 1000-fold, 104-fold, 105-fold or more, as compared to the activity of regulatory T cells in the subject (or particular site in the subject) prior to administration of the compositions. In some embodiments, administration of the compositions described herein results in an increase in activity of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, 1000-fold, 104-fold, 105-fold or more, as compared to the activity of regulatory T cells in another subject (e.g., a reference subject) who did not receive the compositions.


In some embodiments, administration of the compositions described herein results in an increase in the activity of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by at least 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%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150% or more, as compared to the activity of regulatory T cells in the subject (or particular site in the subject) prior to administration of the compositions. In some embodiments, administration of the compositions described herein results in an increase in the activity of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) by at least 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%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150% or more, as compared to the activity of regulatory T cells in another subject (e.g., a reference subject) who did not receive the compositions.


The abundance of regulatory T cells (e.g., total Tregs or pathogenic organism-specific Tregs) can be assessed by any method known in the art, for example by detecting a cellular marker indicative of regulatory T cells (e.g., FoxP3), assessing a direct or indirect activity of regulatory T cells, and/or by measuring the production of one or more cytokines produced by regulatory T cells (e.g., IL-10).


Some aspects compositions and methods described herein increase production of short chain fatty acids (e.g., in the gastrointestinal tract of the subject). In some embodiments, the methods involve administering to a subject one or more compositions containing bacterial strains that produce short chain fatty acids. SCFAs are abundant in healthy subjects (e.g., subjects not having a pathogenic organism infection) and decreased in subjects having pathogenic organism infections (e.g., Clostridium difficile infections and rCDIs). Fecal matter transplant (FMT) have been shown to increase SCFA following rCDI (Seckatz, et al., Anaerobe (2018) 53: 64-73.


SCFA produced in the gastrointestinal tract are thought to function as signaling molecules between the gut microbiota and the host organism, with the SCFA playing a in local, intermediary and peripheral metabolism of the host. Sec, e.g., Morrison, et al. Gut Microbes (2016) 7(3): 189-200. In some embodiments, a damaged gut mucosal barrier can be repaired by providing SCFA.


Examples of SCFA include, without limitation, formic acid, acetic acid, butyric acid, isobutyric acid, valeric acid, or isovaleric acid. In some embodiments, the SCFA is butyric acid (butyrate).


The production of SCFAs and corresponding decolonization of pathogenic organisms are intricately related. In some embodiments, administration of the compositions described herein results in an increase in the production and/or accumulation of SCFAs (e.g., total SCFAs or pathogenic organism-specific SCFAs) by between 1% and 20%, 2% and 19%, 3% and 17%, 4% and 16%, 4% and 15%, 5% and 15%, 6% and 14%, 7% and 13%, 8% and 12%, 5% and 10%, 5% and 15%, 10% and 15%, or 8% and 15% as compared to the quantity of SCFAs in the subject (or particular site in the subject) prior to administration of the compositions. In some embodiments, administration of the compositions described herein results in an increase in the production and/or accumulation of SCFAs (e.g., total SCFAs or pathogenic organism-specific SCFAs) by between 1% and 20%, 2% and 19%, 3% and 17%, 4% and 16%, 4% and 15%, 5% and 15%, 6% and 14%, 7% and 13%, 8% and 12%, 5% and 10%, 5% and 15%, 10% and 15%, or 8% and 15% as compared to the quantity of SCFAs in another subject (e.g., a reference subject) who did not receive the compositions.


In some embodiments, the compositions and methods described herein result in an increase in the amount of SCFAs produced in the gastrointestinal tract of the subject. In some embodiments, the SCFAs are increased by 10-fold to 500-fold following administration of the composition as described herein. In some embodiments, SCFAs are increased by 20-fold to 250-fold following administration of the compositions described herein. In some embodiments, SCFAs are increased by 100-fold to 500-fold following administration of the compositions described herein. In some embodiments, SCFAs are increased by at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold following administration of the compositions described herein.


In some embodiments, SCFAs comprise butyrate. In some embodiments, the level of butyrate (e.g., in the gastrointestinal tract of the subject) is increased by 10-fold to 500-fold following administration of the compositions described herein. In some embodiments, the level of butyrate is increased by 20-fold to 250-fold following administration of compositions described herein. In some embodiments, the level of butyrate is increased by 100-fold to 500-fold following administration of the compositions described herein. In some embodiments, the level of butyrate is increased by at least 2-fold, 5-fold 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold following administration of the compositions described herein.


In some embodiments, SCFAs comprise propionate. In some embodiments, the level of propionate (e.g., in the gastrointestinal tract of the subject) is increased by 10-fold to 500-fold following administration of the compositions described herein. In some embodiments, the level of propionate is increased by 20-fold to 250-fold following administration of compositions described herein. In some embodiments, the level of propionate is increased by 100-fold to 500-fold following administration of the compositions described herein. In some embodiments, the level of propionate is increased by at least 2-fold, 5-fold 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold following administration of the compositions described herein.


In some embodiments, SCFAs comprise acetate. In some embodiments, the level of acetate (e.g., in the gastrointestinal tract of the subject) is increased by 10-fold to 500-fold following administration of the compositions described herein. In some embodiments, the level of acetate is increased by 20-fold to 250-fold following administration of compositions described herein. In some embodiments, the level of acetate is increased by 100-fold to 500-fold following administration of the compositions described herein. In some embodiments, the level of acetate is increased by at least 2-fold, 5-fold 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold following administration of the compositions described herein.


In some embodiments, SCFAs comprise formate. In some embodiments, the level of acetate (e.g., in the gastrointestinal tract of the subject) is increased by 10-fold to 500-fold following administration of the compositions described herein. In some embodiments, the level of formate is increased by 20-fold to 250-fold following administration of compositions described herein. In some embodiments, the level of formate is increased by 100-fold to 500-fold following administration of the compositions described herein. In some embodiments, the level of formate is increased by at least 2-fold, 5-fold 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, 200-fold, 300-fold, 400-fold, or 500-fold following administration of the compositions described herein.


In some embodiments, the subject is infected with a pathogenic organism. In some embodiments, the subject has a Clostridium difficile infection (CDI). In some embodiments, the CDI is recurrent (rCDI). rCDI is CDI that occurs more than once in the same subject and is associated with reduced short chain fatty acids (SCFAs), increased primary bile acids, and decreased secondary bile acids in the gut microbiota of the subject.


Bile acids are steroid acids that allow the digestion of dietary fats and oils by acting as surfactants that turn the fats and oils into micelles. Bile acids also act as hormones utilizing the farnesoid X receptor and GBPAR1. Primary bile acids are synthesized in the liver from cholesterol and a conjugated with either taurine or glycine prior to secretion. When the primary bile acids are secreted into the lumen of the intestine, bacteria partially dehydroxylate and remove the glycine or taurine groups, forming secondary bile acids.


Non-limiting examples of primary bile acids are cholic acid (CA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and turochenodeoxycholic acid (TCDCA). Non-limiting examples of secondary bile acids are deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), taurodeoxycholic acid (TDCA), taurolithocholic acid (TLCA), and tauroursodeoxycholic acid (TUDCA).


Pathogenic organism infection, including Clostridium difficile infection and rCDI, are associated with increased primary bile acids and reduced secondary bile acids. The primary bile acids are reduced, and the secondary bile acids are increased following fecal matter transplant (FMT) (Seckatz, et al., Anaerobe (2018) 53: 64-73). In some embodiments, administration of the bacterial strains or a pharmaceutical composition as described herein reduces primary bile acids and/or increases secondary bile acids.


In some embodiments, the levels of primary bile acids are reduced by 10-fold to 100,000-fold following administration of the bacterial strains or the pharmaceutical composition. In some embodiments, the levels of primary bile acids are reduced by 10-fold to 1,000-fold following administration of the bacterial strains or the pharmaceutical composition. In some embodiments, the levels of primary bile acids are reduced 20-fold to 10,000-fold following administration of the bacterial strains or the pharmaceutical composition. In some embodiments, the levels of primary bile acids are reduced by 10-fold, 100-fold, 200-fold, 300-fold, 400-fold, 500-fold, 600-fold, 700-fold, 800-fold, 900-fold, 1,000-fold, 10,000-fold, 20,000-fold, 30,000-fold, 40,000-fold, 50,000-fold, 60,000-fold, 70,000-fold, 80,000-fold, 90,000-fold, or 100,000-fold following administration of the bacterial strains or the pharmaceutical composition.


In some embodiments, the levels of secondary bile salts are increased by 10-fold to 10,000-fold following administration of the bacterial strains or the pharmaceutical composition. In some embodiments, the levels of secondary bile acids are increased by 10-fold to 1,000-fold following administration of the bacterial strains or the pharmaceutical composition. In some embodiments, the levels of secondary bile acids are increased by 20-fold to 100-fold following administration of the bacterial strains or the pharmaceutical composition. In some embodiments, the levels of secondary bile acids are increased by 10-fold, 20-fold, 50-fold, 100-fold, 200-fold, 300-fold, 400-fold, 500-fold, 600-fold, 700-fold, 800-fold, 900-fold, 1,000-fold, 2,000-fold, 3,000-fold, 4,000-fold, 5,000-fold, 6,000-fold, 7,000-fold, 8,000-fold, 9,000-fold, or 1,000-fold following administration of the bacterial strains or the pharmaceutical composition.


In general, short chain fatty acids (SCFAs) are fatty acids containing six or less carbon atoms. SCFAs are produced when dietary fiber is fermented in the intestine. Non-limiting examples of SCFAs include hexanoate, pentanoate, butyrate, propionate, acetate, and formate. SCFAs are primarily absorbed in the portal vein following lipid digestion, and can affect the production of lipids, energy, and vitamins. Further, SCFAs play a critical role in maintaining intestinal epithelial cell membrane integrity for preventing pathogenic organism (e.g., Clostridium difficile) infection.


In one aspect, the disclosure provides methods comprising administration of multiple doses of the pharmaceutical compositions. In some embodiments, the disclosure provides methods comprising administration of antibiotic (e.g., vancomycin) followed by multiple doses of the pharmaceutical compositions. In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides enhanced colonization (engraftment) of one or more bacterial strains of the pharmaceutical compositions as compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides enhanced recovery of one or more bacterial strains of the pharmaceutical compositions as compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides increased abundance of one or more bacterial strains of the pharmaceutical compositions as compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides an increase in the number of subjects that were colonized with of all of bacterial strains of the pharmaceutical compositions as compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides durable colonization (e.g., up to 6 months) of one or more bacterial strains of the pharmaceutical compositions as compared to administration of a single dose of the pharmaceutical composition. In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides durable colonization (e.g., up to 6 months) of all of the bacterial strains of the pharmaceutical compositions as compared to administration of a single dose of the pharmaceutical composition. It should further be appreciated that administration of multiple dose my results in a combination of the results described. Thus, for example, in some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides enhanced colonization (engraftment) and increased rate of recovery of one or more bacterial strains of the pharmaceutical compositions as compared to administration of a single dose of the pharmaceutical composition.


In some embodiments, administration of multiple doses of the pharmaceutical compositions described herein provides enhanced colonization (engraftment) of one or more bacterial strains of the pharmaceutical compositions as compared to administration of a single dose of the pharmaceutical composition. Administration of multiple doses of the pharmaceutical composition may result in enhanced colonization (engraftment) and an increased abundance of each of the bacterial strains of the pharmaceutical composition. In some embodiments, administration of a single dose of the pharmaceutical composition results in the same or a similar level of engraftment (e.g., total bacteria) as administration of multiple doses of the pharmaceutical composition, however the engraftment may be dominated by one bacterial strain or only a subset of the bacterial strains of the pharmaceutical compositions.


Any of the methods described herein may involve administering an antibiotic to the subject prior to administration of the pharmaceutical compositions described herein. In some embodiments, the antibiotic is vancomycin, fidaxomycin or ridinilazole. Non-limiting examples of antibiotics that may be used in any of the methods provided herein include cephalosporin antibiotics cephalexin, cefuroxime, cefadroxil, cefazolin, cephalothin, cefaclor, cefamandole, cefoxitin, cefprozil, ceftobiprole, clindamycin, ceftriaxone, cefotaxime, cefazolin, cefoperazone, cefuroxime, cefmetazole, fluoroquinolone, ciprofloxacin, Levaquin, floxin, tequin, avelox, norflox, tetracycline, minocycline, oxytetracycline, doxycycline, amoxicillin, ampicillin, penicillin V, dicloxacillin, benzylpenicillin, carbenicillin, vancomycin, and methicillin, ertapenem, doripenem, imipenem/cilastatin, meropenem, clavulanate, tazobactam, piperacillin, ceftriaxone, cefotaxime, cefazolin, fluoroquinolone, imipenem, meropenem, metronidazole, fidaxomyxin, or ridinilazole.


In some embodiments, any of the methods described herein may further comprise administering vancomycin to the subject prior to administration of the pharmaceutical compositions described herein. In some embodiments, the method does not comprise administering an antibiotic to the subject prior to administration of the pharmaceutical compositions described herein. In some embodiments, the method does not comprise administering vancomycin to the subject prior to administration of the pharmaceutical compositions described herein. Vancomycin administration has been found to alter the composition of human gut microbiota. See, e.g., Reijnders et al. Cell Metabolism (2016) 24(1): 63-72. Without wishing to be bound by any particular theory, it is thought that administration of vancomycin may aid engraftment of the bacterial strain(s) of the pharmaceutical compositions described herein, for example by removing other microbes present in the gastrointestinal tract.


In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject once, as a single dose. In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject in multiple doses. In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject in at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. The multiple doses of the antibiotic (e.g., vancomycin) may be administered to the subject at regular intervals prior to administering any of the pharmaceutical compositions described herein. In some embodiments, each of the multiple doses of the antibiotic (e.g., vancomycin) are administered on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.). In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more consecutive days. In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject each day for three consecutive days. In some embodiments, the antibiotic (e.g., vancomycin) administered to the subject each day for five consecutive days.


In some embodiments, the antibiotic (e.g., vancomycin) administered to the subject each day for seven consecutive days. In some embodiments, the antibiotic (e.g., vancomycin) administered to the subject for one day. In any of the embodiments described herein, a subject may be administered one or more doses of a first antibiotic followed by one or more doses of a second antibiotic.


In some embodiments, a single dose, or the first dose in a treatment regimen of multiple doses, is administered, the same day as the administration of the final dose of the antibiotic (e.g., vancomycin). In some embodiments, a single dose, or the first dose in a treatment regimen of multiple doses, is administered, the day after administration of the final dose of the antibiotic (e.g., vancomycin). In some embodiments, a single dose, or the first dose in a treatment regimen of multiple doses, is administered, two days after administration of the final dose of the antibiotic (e.g., vancomycin). In some embodiments, the methods provided herein allow for a wash out day between the final dose of the antibiotic (e.g., vancomycin) and the first dose of the pharmaceutical composition. In some embodiments, a single dose, or the first dose in a treatment regimen of multiple doses, is administered, three days, four days, five days, six days, ten days or more, after administration of the final dose of the antibiotic (e.g., vancomycin). In some embodiments, the methods provided herein allow for multiple wash out days between the final dose of the antibiotic (e.g., vancomycin) and the first dose of the pharmaceutical composition.


Each dose of the antibiotic (e.g., vancomycin) may be the same amount of the antibiotic or may be a different amount of the antibiotic. In some embodiments, the antibiotic (e.g., vancomycin) is administered in an amount sufficient to allow for colonization of one or more of the bacterial strains of the pharmaceutical compositions described herein. In some embodiments, the subject is administered between about 50 mg and 1 g, 100 mg and 750 mg, 100 mg and 500 mg. 200 mg and 750 mg. 200 mg and 500 mg, 300 mg and 750 mg, 300 mg and 500 mg, 100 mg and 400 mg, 100 mg and 300 mg, 100 mg and 200 mg, 200 mg and 400 mg. 200 mg and 300 mg, or 450 mg to 550 mg of the antibiotic per day. As will be appreciated by one of skill in the art, the total amount of vancomycin administered to the subject per day may be administered in a single dose or between multiple doses, which in sum results in the total amount of the antibiotic per day.


In some example, the subject is administered about 500 mg vancomycin per day prior to administration of any of the pharmaceutical compositions described herein. In some embodiments, 500 mg of vancomycin per day is administered in a single dose (e.g., 500 mg). In some embodiments, 500 mg of vancomycin per day is administered in multiple doses (e.g., 2, 3, 4, 5 or more), which in sum results in 500 mg vancomycin per day. In some embodiments, 500 mg vancomycin is administered in 4 doses of 125 mg vancomycin per day. In some embodiments, 500 mg of vancomycin is administered to the subject for one day. In some embodiments, 500 mg of vancomycin is administered to the subject per day for two days. In some embodiments, 500 mg vancomycin is administered to the subject per day for three days. In some embodiments, 500 mg vancomycin is administered to the subject per day for four days. In some embodiments, 500 mg vancomycin is administered to the subject per day for five days. In some embodiments, 500 mg vancomycin is administered to the subject per day for six days. In some embodiments, 500 mg vancomycin is administered to the subject per day for seven days. In some embodiments, 500 mg vancomycin is administered to the subject per day for eight days. In some embodiments, 500 mg vancomycin is administered to the subject per day for nine days. In some embodiments, 500 mg vancomycin is administered to the subject per day for ten days.


In some embodiments, the subject is administered about 250 mg vancomycin per day prior to administration of any of the pharmaceutical compositions described herein. In some embodiments, 250 mg vancomycin per day is administered in a single dose (e.g., 250 mg). In some embodiments, 250 mg vancomycin per day is administered in multiple doses (e.g., 2, 3, 4, 5 or more), which in sum results in 250 mg vancomycin per day. In some embodiments, 250 mg vancomycin is administered in 2 doses of 125 mg vancomycin per day. In some embodiments, 250 mg vancomycin is administered to the subject for one day. In some embodiments, 250 mg vancomycin is administered to the subject per day for two days. In some embodiments, 250 mg vancomycin is administered to the subject per day for three days. In some embodiments, 250 mg vancomycin is administered to the subject per day for four days. In some embodiments, 250 mg vancomycin is administered to the subject per day for five days. In some embodiments, 250 mg vancomycin is administered to the subject per day for six days. In some embodiments, 250 mg vancomycin is administered to the subject per day for seven days. In some embodiments, 250 mg vancomycin is administered to the subject per day for eight days. In some embodiments, 250 mg vancomycin is administered to the subject per day for nine days. In some embodiments, 250 mg vancomycin is administered to the subject per day for ten days.


In some embodiments, the subject is administered about 125 mg vancomycin per day prior to administration of any of the pharmaceutical compositions described herein. In some embodiments, the 125 mg vancomycin per day is administered in a single dose (e.g., 125 mg). In some embodiments, the 125 mg vancomycin per day is administered in multiple doses (e.g., 2, 3, 4, 5 or more), which in sum results in 125 mg vancomycin per day. In some embodiments, 125 mg vancomycin is administered to the subject for one day. In some embodiments, 125 mg vancomycin is administered to the subject per day for two days. In some embodiments, 125 mg vancomycin is administered to the subject per day for three days. In some embodiments, 125 mg vancomycin is administered to the subject per day for four days. In some embodiments, 125 mg vancomycin is administered to the subject per day for five days. In some embodiments, 125 mg vancomycin is administered to the subject per day for six days. In some embodiments, 125 mg vancomycin is administered to the subject per day for seven days. In some embodiments, 125 mg vancomycin is administered to the subject per day for eight days. In some embodiments, 125 mg vancomycin is administered to the subject per day for nine days. In some embodiments, 125 mg vancomycin is administered to the subject per day for ten days.


In some embodiments, the disclosure provides methods comprising administering one or more antibiotics to the subject and subsequently administering any of the bacterial compositions to the subject once, twice, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, or at least 10 times, or more. In some embodiments, the disclosure provides methods comprising administering one or more antibiotics to the subject and subsequently administering any of the bacterial compositions described herein to the subject in multiple doses at a regular interval, such as every 2 weeks, every month, every 2 months, every 3 months, every 4 months, every 5 months, every 6 months, or more. In some embodiments, one dose of any of the compositions described herein is administered and a second dose of the composition is administered the following day (e.g., consecutive day). In some embodiments, one dose of any of the compositions described herein is administered and each of the additional doses of the composition are administered on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.).


In one aspect, the disclosure provides methods comprising administering one or more antibiotics to the subject and subsequently administering any of the bacterial compositions as multiple daily doses of the pharmaceutical compositions. In some embodiments, the pharmaceutical compositions are administered on a daily basis for 2 days, 3 days, 4, days, 5, days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months or more. In some embodiments, the antibiotic (e.g., vancomycin) is administered according to a pulse tapered regime. See e.g., Sirbu et al., Clinical Infectious Diseases (2017) 65: 1396-1399.


In some embodiments, the antibiotic (e.g., vancomycin) is administered to the subject at least 1, 2, 3, 4, 5, 6, 7 days or more prior to administration of the pharmaceutical compositions described herein. In some embodiments, administration of antibiotic (e.g., vancomycin) is terminated at least one day (e.g., 1, 2, 3, 4, 5, or more) prior to administration of any of the pharmaceutical compositions described herein.


In some embodiments, additional antibiotics are administered in combination with the vancomycin regimes provided herein.


It should be appreciated, in some embodiments, that any of the vancomycin doses or administration regimens may be combined with any of the pharmaceutical composition doses or administration regimens provided herein.


In one aspect the disclosure provides methods comprising the administration of an antibiotic (e.g., vancomycin) followed by the administration of a pharmaceutical composition provided herein, wherein the administration of an antibiotic (e.g., vancomycin) is followed by the administration of a single dose or multiple doses of the pharmaceutical composition. In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of a single dose or multiple doses of the pharmaceutical composition results in an increase in the abundance of bacterial strains of the pharmaceutical compositions in the microbiome of the subject (engraftment) compared to the administration of a pharmaceutical composition without the administration of the antibiotic. In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of a single dose or multiple doses of the pharmaceutical composition results in an increase in the duration of the colonization of bacterial strains of the pharmaceutical composition in the microbiome of the subject (e.g., up to 6 months) compared to the administration of a pharmaceutical composition without the administration of the antibiotic.


In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of a single dose or multiple doses of the pharmaceutical composition results in an increase in the rate of engraftment of the initial amount of the bacterial strains of the pharmaceutical composition in the microbiome of the subject by between ten- to one hundred-fold (e.g., within the first 48 hours) compared to the administration of a pharmaceutical composition without the administration of the antibiotic.


In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of a single dose or multiple doses of the pharmaceutical composition results in a greater number (amount) of subjects having all of the bacterial strains of the pharmaceutical composition present in their microbiome as compared to compared to the administration of a pharmaceutical composition without the administration of the antibiotic.


In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of multiple doses of the pharmaceutical composition results in an increase in the abundance of bacterial strains of the pharmaceutical composition in the microbiome of the subject (engraftment) compared to the administration of a single dose of the pharmaceutical composition. In some embodiments, the disclosure provides methods comprising the administration of a pharmaceutical composition provided herein, wherein the administration of multiple doses of the pharmaceutical composition increases the abundance of bacterial strains in the microbiota of the subject (engraftment) of the pharmaceutical composition in the microbiome of the subject compared to the administration of a single dose of the pharmaceutical composition.


In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of multiple doses of the pharmaceutical composition results in an increase in the rate of engraftment of the initial amount of the bacterial strains of the pharmaceutical composition in the microbiome of the subject as compared to the administration of a single dose of the pharmaceutical composition. In some embodiments, the disclosure provides methods comprising the administration of a pharmaceutical composition provided herein, wherein the administration of multiple doses of the pharmaceutical composition increases the rate of engraftment of the initial amount of the bacterial strains of the pharmaceutical composition in the microbiome of the subject compared to the administration of a single dose of the pharmaceutical composition.


In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of multiple doses of the pharmaceutical composition results in a higher abundance of the bacterial strains of the pharmaceutical composition in the microbiome of the subject as compared to the administration of a single dose of the pharmaceutical composition. In some embodiments, the disclosure provides methods comprising the administration of a pharmaceutical composition provided herein, wherein the administration of multiple doses of the pharmaceutical composition results in higher abundance of the bacterial strains of the pharmaceutical composition in the microbiome of the subject compared to the administration of a single dose of the pharmaceutical composition.


In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of multiple doses of the pharmaceutical composition results in a greater number (amount) of subjects having all of the bacterial strains of the pharmaceutical composition present in their microbiome as compared to the administration of a single dose of the pharmaceutical composition. In some embodiments, the disclosure provides methods comprising the administration of a pharmaceutical composition provided herein, wherein the administration of multiple doses of the pharmaceutical results in a greater number (amount) of subject having all of the bacterial strains of the pharmaceutical composition in their microbiome as compared to the administration of a single dose of the pharmaceutical composition.


In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of multiple doses of the pharmaceutical composition results in an accelerated recovery of the microbiome (e.g., increase in bacterial species of Bacteroidetes and/or Firmicutes, and/or decrease in Proteobacteria) as compared to the administration of a single dose of the pharmaceutical composition. In some embodiments, the disclosure provides methods comprising the administration of a pharmaceutical composition provided herein, wherein the administration of multiple doses of the pharmaceutical results in an accelerated recovery of the microbiome (e.g., increase in bacterial species of Bacteroidetes and/or Firmicutes, and/or decrease in Proteobacteria) as compared the administration of a single dose of the pharmaceutical composition.


In some embodiments, administration of an antibiotic (e.g., vancomycin) followed by the administration of a single dose or multiple doses of the pharmaceutical composition results in an accelerated recovery of the microbiome (e.g., increase in bacterial species of Bacteroidetes and/or Firmicutes, and/or decrease in Proteobacteria) as compared to the administration of an antibiotic (e.g., vancomycin) without the administration of a pharmaceutical composition.


In some embodiments, any of the methods described herein may further comprise administering a composition comprising taurine to the subject. In some embodiments, the composition comprising taurine is administered concomitantly with any of the pharmaceutical compositions comprising a purified bacterial mixture described herein. In some embodiments, the composition comprising taurine is administered prior to administration of any of the pharmaceutical compositions comprising a purified bacterial mixture described herein. In some embodiments, the composition comprising taurine is administered after administration of any of the pharmaceutical compositions comprising a purified bacterial mixture described herein. In some embodiments, the composition comprising taurine is administered prior to and after administration of any of the pharmaceutical compositions comprising a purified bacterial mixture described herein.


Taurine, also referred to as 2-aminoethanesulfonic acid, is an organic compound that is widely distributed in animal tissues and is a major constituent of bile and can be found conjugated to bile acids. Taurine may account for up to 0.1% of total human body weight and can be found in the large intestine, among other locations. The precise function of taurine in the physiological processes is not known, but without wishing to be bound by any particular theory, it is thought that taurine may help support muscle maintenance.


Taurine occurs naturally in fish and meat, and consumption in humans generally varies between 40 and 400 mg per day. However, in recent years, energy drinks for human consumption have included taurine. One example energy drink, marketed under the trademark Red Bull®, contains approximately 1000 mg of taurine per can (serving). High consumption of taurine is generally considered to be safe with no adverse effects noted from up to 3000 mg taurine per day.


Taurine administration has been found to alter the composition of mouse gut microbiota. It has recently been reported that infection may induce host taurine production and the expansion of taurine utilizers. Upon release of bile acids from the gallbladder into the gut, bacteria present in the gut may cleave taurine from bile acids, making the taurine available for use as an energy source. Bacteria, for example of the class Deltaproteobacteria, such as Biophila wadsworthia, utilize taurine in anaerobic respiration, and the expansion of Deltaproteobacteria following taurine administration is thought to aid in inhibiting intestinal colonization by Klebsiella pneumoniae and Citrobacter rodentium, a mouse model of pathogenic E. coli. Sec, e.g., Stacy et al. Cell. 2021 184(3):615-627.


As a result, gut microbiota from previously infected hosts were found to display enhanced resistance to infection. The microbiota from previously infected hosts has been associated with altered bile acid metabolism leading to the expansion of taxa that utilize the sulfonic acid, taurine. Indeed, it was reported that supplying exogenous taurine alone was sufficient to induce this alteration in microbiota function and enhance resistance. Mechanistically, taurine potentiates the microbiota's production of sulfide, an inhibitor of cellular respiration, which is key to host invasion by numerous pathogens. Sec, e.g., Stacy et al. Cell. 2021 184(3):615-627.


Without wishing to be bound by any particular theory, it is thought that administration of taurine may promote replication and/or aid engraftment of the bacterial strain(s) of the pharmaceutical compositions described herein, for example by serving as an energy source for bacteria present in the gastrointestinal tract or pharmaceutical composition.


In some embodiments, compositions comprising at least two of the strains selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri in combination with taurine may be effective at inhibiting infection and/or reducing/preventing colonization with a pathogen that is more than additive of either taurine alone or the bacterial compositions alone.


As described herein, any of the bacterial compositions may further comprise taurine. In such embodiments, the bacterial strain and taurine are administered to the subject at the same time. In some embodiments, taurine is administered to the subject in a separate composition, such as a pharmaceutical composition or food product, including beverage product.


In some embodiments, the composition comprises between about 40 mg to about 3000 mg taurine. In some embodiments, the composition comprises between about 100 mg to about 2000 mg taurine. In some embodiments, the composition comprises between about 500 mg to about 1500 mg taurine.


In some embodiments, the compositions comprising bacterial strains also comprise taurine. In some embodiments, the composition comprises about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg. 2100 mg, 2200 mg, 2300 mg, 2400 mg, 2500 mg, 2600 mg, 2700 mg, 2800 mg, 2900 mg, or 3000 mg taurine.


In some embodiments, the subject is administered between about 40 mg to about 3000 mg of taurine per day. In some embodiments, the subject is administered between about 100 mg to about 2000 mg taurine per day. In some embodiments, the subject is administered between about 500 mg to about 1500 mg taurine per day. Any of the daily amounts of taurine may be administered to the subject as a single dosage or as multiple dosages across the day.


In some embodiments, a composition comprising taurine is administered to the subject once, as a single dose. In some embodiments, the composition comprising taurine is administered to the subject in multiple doses. In some embodiments, the composition comprising taurine is administered to the subject in at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses.


One or more doses of a composition comprising taurine may be administered to the subject prior to administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered in multiple doses, such as on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.) prior to administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered to the subject for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more consecutive days prior to administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered to the subject each day for three consecutive days prior to administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, the composition comprising taurine is administered to the subject each day for five consecutive days prior to administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered to the subject each day for seven consecutive days prior to administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered to the subject for one day prior to administering any of the pharmaceutical compositions containing purified bacterial strains described herein.


One or more doses of a composition comprising taurine may be administered to the subject after administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered in multiple doses, such as on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.) after administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered to the subject for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more consecutive days after administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered to the subject each day for three consecutive days after administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, the composition comprising taurine is administered to the subject each day for five consecutive days after administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered to the subject each day for seven consecutive days after administering any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered to the subject for one day after administering any of the pharmaceutical compositions containing purified bacterial strains described herein.


In some embodiments, a composition comprising taurine is administered the same day as the administration of any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered at the same time (simultaneously) or substantially at the same time as the administration of any of the pharmaceutical compositions containing purified bacterial strains described herein. In some embodiments, a composition comprising taurine is administered within 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours of the administration of any of the pharmaceutical compositions containing purified bacterial strains described herein.


The composition comprising taurine may in any form for human administration, such as a food product/beverage, capsule, pill, tablet, or liquid composition.


In some embodiments, the methods described herein may involve subjecting the subject to a bowel lavage (bowel irrigation, whole bowel irrigation, gastrointestinal lavage, gastric lavage) prior to administration of the compositions described herein. In some embodiments, a bowel lavage may remove or aid in removing microbiota from the gastrointestinal tract of the subject, creating a niche for the bacterial strains of the compositions described herein. In some embodiments, the bowel lavage may be an oral bowel lavage or a rectal bowel lavage.


Methods of performing a bowel lavage are known in the art, and generally involve the rapid administration of large volumes of a solution, such as polyethylene glycol or a balanced electrolyte solution. A rectal bowel lavage can involve the administration of a solution or a suppository containing the pharmaceutical composition. A bowel lavage may be performed under doctor supervision, hospitalization, or at home.


Any of the compositions described herein, including the pharmaceutical compositions and food products comprising the compositions, may contain bacterial strains in any form, for example in an aqueous form, such as a solution or a suspension, embedded in a semi-solid form, in a powdered form or freeze dried form. In some embodiments, the composition or the bacterial strains of the composition are lyophilized. In some embodiments, a subset of the bacterial strains in a composition is lyophilized. Methods of lyophilizing compositions, specifically compositions comprising bacteria, are well known in the art. Sec, e.g., U.S. Pat. Nos. 3,261,761; 4,205,132; PCT Publications WO 2014/029578 and WO 2012/098358, herein incorporated by reference in their entirety. The bacteria may be lyophilized as a combination and/or the bacteria may be lyophilized separately and combined prior to administration. A bacterial strain may be combined with a pharmaceutical excipient prior to combining it with the other bacterial strain or multiple lyophilized bacteria may be combined while in lyophilized form and the mixture of bacteria, once combined may be subsequently be combined with a pharmaceutical excipient. In some embodiments, the bacterial strain is a lyophilized cake. In some embodiments, the compositions comprising the one or more bacterial strains are a lyophilized cake.


In some embodiments, one or more of the bacterial strains of the compositions, including pharmaceutical compositions and food products, has been spray-dried. In some embodiments, a subset of the bacterial strains is spray-dried. The process of spray-drying refers to production of dry powder from a liquid comprising bacterial compositions (Sec, e.g., Ledet, et al., Spray Draying of Pharmaceuticals in “Lyophilized Biologics and Vaccines” pages 273-294, Springer). In general, the process involves rapidly drying the bacterial compositions with a hot gas. A bacterial strain may be combined with a pharmaceutical excipient prior to combining it with the other bacterial strains or multiple spray-dried bacterial strains may be combined while in spray-dried form and the mixture of bacterial strains, once combined, may be subsequently combined with a pharmaceutical excipient.


The bacterial strains of the composition can be manufactured using fermentation techniques well known in the art. In some embodiments, the active ingredients are manufactured using anaerobic fermenters, which can support the rapid growth of anaerobic bacterial species. The anaerobic fermenters may be, for example, stirred tank reactors or disposable wave bioreactors. Culture media such as BL media and EG media, or similar versions of these media devoid of animal components, can be used to support the growth of the bacterial species. The bacterial product can be purified and concentrated from the fermentation broth by traditional techniques, such as centrifugation and filtration, and can optionally be dried and lyophilized by techniques well known in the art.


In some embodiments, the composition of bacterial strains may be formulated for administration as a pharmaceutical composition. The term “pharmaceutical composition” as used herein means a product that results from the mixing or combining of at least one active ingredient, such as any two or more purified bacterial strains described herein, and one or more inactive ingredients, which may include one or more pharmaceutically acceptable excipient.


An “acceptable” excipient refers to an excipient that must be compatible with the active ingredient and not deleterious to the subject to which it is administered. In some embodiments, the pharmaceutically acceptable excipient is selected based on the intended route of administration of the composition, for example a composition for oral or nasal administration may comprise a different pharmaceutically acceptable excipient than a composition for rectal administration. Examples of excipients include sterile water, physiological saline, solvent, a base material, an emulsifier, a suspending agent, a surfactant, a stabilizer, a flavoring agent, an aromatic, an excipient, a vehicle, a preservative, a binder, a diluent, a tonicity adjusting agent, a soothing agent, a bulking agent, a disintegrating agent, a buffer agent, a coating agent, a lubricant, a colorant, a sweetener, a thickening agent, and a solubilizer.


Pharmaceutical compositions disclosed herein can be prepared in accordance with methods well known and routinely practiced in the art (see e.g., Remington: The Science and Practice of Pharmacy, Mack Publishing Co. 20th ed. 2000). The pharmaceutical compositions described herein may further comprise any carriers or stabilizers in the form of a lyophilized formulation or an aqueous solution. Acceptable excipients, carriers, or stabilizers may include, for example, buffers, antioxidants, preservatives, polymers, chelating reagents, and/or surfactants. Pharmaceutical compositions are preferably manufactured under GMP conditions. The pharmaceutical compositions can be used orally, nasally or parenterally, for instance, in the form of capsules, tablets, pills, sachets, liquids, powders, granules, fine granules, film-coated preparations, pellets, troches, sublingual preparations, chewables, buccal preparations, pastes, syrups, suspensions, elixirs, emulsions, liniments, ointments, plasters, cataplasms, transdermal absorption systems, lotions, inhalations, aerosols, injections, suppositories, and the like. In some embodiments, the pharmaceutical compositions can be used by injection, such as by intravenous, intramuscular, subcutaneous, or intradermal administration.


Aspects of the present disclosure relate to administration of compositions comprising taurine. In some embodiments, a composition comprising any of the purified bacterial strains described herein may further comprise taurine. In such embodiments, administration of the composition results in administration to the subject of both the purified bacterial strains and taurine. In some embodiments, a composition comprising any of the purified bacterial strains described herein does not contain taurine. In some embodiments, a composition that is not the composition comprising the purified bacterial strains comprises taurine. In some embodiments, the methods involve administering to a subject a composition comprising purified bacterial strains and administering to the subject a second composition comprising taurine.


In some embodiments, the compositions comprising bacterial strains are formulated for delivery to the intestines (e.g., the small intestine and/or the colon). In some embodiments, the compositions comprising bacterial strains are formulated with an enteric coating that increases the survival of the bacteria through the harsh environment in the stomach. The enteric coating is one which resists the action of gastric juices in the stomach so that the bacteria of the composition therein will pass through the stomach and into the intestines. The enteric coating may readily dissolve when in contact with intestinal fluids, so that the bacteria enclosed in the coating will be released in the intestinal tract. Enteric coatings may consist of polymer and copolymers well known in the art, such as commercially available EUDRAGIT (Evonik Industries). (See e.g., Zhang, AAPS PharmSciTech (2016) 17(1): 56-67).


The compositions comprising bacterial strains may also be formulated for rectal delivery to the intestine (e.g., the colon). Thus, in some embodiments, compositions comprising bacterial strains may be formulated for delivery by suppository, colonoscopy, endoscopy, sigmoidoscopy or enema. A pharmaceutical preparation or formulation and particularly a pharmaceutical preparation for oral administration, may include an additional component that enables efficient delivery of the compositions of the disclosure to the intestine (e.g., the colon). A variety of pharmaceutical preparations that allow for the delivery of the compositions to the intestine (e.g., the colon) can be used. Examples thereof include pH sensitive compositions, more specifically, buffered sachet formulations or enteric polymers that release their contents when the pH becomes alkaline after the enteric polymers pass through the stomach. When a pH sensitive composition is used for formulating the pharmaceutical preparation, the pH sensitive composition is preferably a polymer whose pH threshold of the decomposition of the composition is between about 6.8 and about 7.5. Such a numeric value range is a range in which the pH shifts toward the alkaline side at a distal portion of the stomach, and hence is a suitable range for use in the delivery to the colon. It should further be appreciated that each part of the intestine (e.g., the duodenum, jejunum, ileum, cecum, colon and rectum), has different biochemical and chemical environment. For instance, parts of the intestines have different pHs, allowing for targeted delivery by compositions that have a specific pH sensitivity. Thus, the compositions provided herein may be formulated for delivery to the intestine or specific parts of the intestine (e.g., the duodenum, jejunum, ileum, cecum, colon and rectum) by providing formulations with the appropriate pH sensitivity. (See e.g., Villena et al., Int J Pharm (2015) 487 (1-2): 314-9).


Another embodiment of a pharmaceutical preparation useful for delivery of the compositions to the intestine (e.g., the colon) is one that ensures the delivery to the colon by delaying the release of the contents (e.g., the bacterial strains) by approximately 3 to 5 hours, which corresponds to the small intestinal transit time. In one embodiment of a pharmaceutical preparation for delayed release, a hydrogel is used as a shell. The hydrogel is hydrated and swells upon contact with gastrointestinal fluid, with the result that the contents are effectively released (released predominantly in the colon). Delayed release dosage units include drug-containing compositions having a material which coats or selectively coats a drug or active ingredient to be administered. Examples of such a selective coating material include in vivo degradable polymers, gradually hydrolyzable polymers, gradually water-soluble polymers, and/or enzyme degradable polymers. A wide variety of coating materials for efficiently delaying the release is available and includes, for example, cellulose-based polymers such as hydroxypropyl cellulose, acrylic acid polymers and copolymers such as methacrylic acid polymers and copolymers, and vinyl polymers and copolymers such as polyvinylpyrrolidone.


Additional examples of pharmaceutical compositions that allow for the delivery to the intestine (e.g., the colon) include bioadhesive compositions which specifically adhere to the colonic mucosal membrane (for example, a polymer described in the specification of U.S. Pat. No. 6,368,586) and compositions into which a protease inhibitor is incorporated for protecting particularly a biopharmaceutical preparation in the gastrointestinal tracts from decomposition due to an activity of a protease.


Another example of a system enabling the delivery to the intestine (e.g., the colon) is a system of delivering a composition to the colon by pressure change in such a way that the contents are released by utilizing pressure change caused by generation of gas in bacterial fermentation at a distal portion of the stomach. Such a system is not particularly limited, and a more specific example thereof is a capsule which has contents dispersed in a suppository base and which is coated with a hydrophobic polymer (for example, ethyl cellulose).


A further example of a system enabling the delivery of a composition to the intestine (e.g., the colon), is a composition that includes a coating that can be removed by an enzyme present in the gut (e.g., the colon), such as, for example, a carbohydrate hydrolase or a carbohydrate reductase. Such a system is not particularly limited, and more specific examples thereof include systems which use food components such as non-starch polysaccharides, amylose, xanthan gum, and azopolymers.


The compositions provided herein can also be delivered to specific target areas, such as the intestine, by delivery through an orifice (e.g., a nasal tube) or through surgery. In addition, the compositions provided herein that are formulated for delivery to a specific area (e.g., the cecum or the colon), may be administered by a tube (e.g., directly into the small intestine). Combining mechanical delivery methods such as tubes with chemical delivery methods such as pH specific coatings, allow for the delivery of the compositions provided herein to a desired target area (e.g., the cecum or the colon).


The compositions comprising bacterial strains are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those of skill in the art. Dosage regimens are adjusted to provide the optimum desired response (e.g., the prophylactic or therapeutic effect). In some embodiments, the dosage form of the composition is a tablet, pill, capsule, powder, granules, solution, or suppository. In some embodiments, the pharmaceutical composition is formulated for oral administration. In some embodiments, the pharmaceutical composition is formulated such that the bacteria of the composition, or a portion thereof, remain viable after passage through the stomach of the subject. In some embodiments, the pharmaceutical composition is formulated for rectal administration, e.g. as a suppository. In some embodiments, the pharmaceutical composition is formulated for delivery to the intestine or a specific area of the intestine (e.g., the colon) by providing an appropriate coating (e.g., a pH specific coating, a coating that can be degraded by target area specific enzymes, or a coating that can bind to receptors that are present in a target area).


Dosages of the active ingredients in the pharmaceutical compositions disclosed herein can be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired pharmaceutical response for a particular subject, composition, and mode of administration, without being toxic or having an adverse effect on the subject. The selected dosage level depends upon a variety of factors including the activity of the particular compositions employed, the route of administration, the time of administration, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the subject being treated, and like factors.


A physician, veterinarian or other trained practitioner, can start doses of the pharmaceutical composition at levels lower than that required to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In general, effective doses of the compositions, for the prophylactic or therapeutic treatment of groups of people as described herein vary depending upon many different factors, including routes of administration, physiological state of the subject, whether the subject is human or an animal, other medications administered, and the therapeutic effect desired. Dosages need to be titrated to optimize safety and efficacy. In some embodiments, the dosing regimen entails oral administration of a dose of any of the compositions described herein. In some embodiments, the dosing regimen entails oral administration of multiple doses of any of the compositions described herein. In some embodiments, the composition is administered orally the subject once, twice, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, or at least 10 times. In some embodiments, any of the compositions described herein are administered the subject in multiple doses at a regular interval, such as every 2 weeks, every month, every 2 months, every 3 months, every 4 months, every 5 months, every 6 months, or more.


The compositions, including the pharmaceutical compositions disclosed herein, include compositions that contain selected bacterial strains. The amount of bacteria, including the amount of bacteria cells of each of the bacterial strains, in the compositions, including pharmaceutical compositions, may be expressed in weight, number of bacteria and/or CFUs (colony forming units). In some embodiments, the compositions, including pharmaceutical compositions, comprise about 10, about 102, about 103, about 104, about 105, about 106, about 107, about 108, about 109, about 1010, about 1011, about 1012, about 1013 or more of each of the bacterial strains per dosage amount. In some embodiments, the compositions, including pharmaceutical compositions, comprise about 10, about 102, about 103, about 104, about 105, about 106, about 107, about 108, about 109, about 1010, about 1011, about 1012, about 1013 or more total bacterial cells per dosage amount. It should further be appreciated that bacteria of each of the bacterial strains may be present in different amounts. Thus, for instance, as a non-limiting example, composition may include 103 of bacteria A, 104 of bacteria B and 106 of bacteria C. In some embodiments, compositions, including pharmaceutical composition, comprise about 10, about 102, about 103, about 104, about 105, about 106, about 107, about 108, about 109, about 1010, about 1011, about 1012, about 1013 or more bacterial cells or CFUs of each of the bacterial strains per dosage amount. In some embodiments, compositions, including pharmaceutical compositions, comprise about 101, about 102, about 103, about 104, about 105, about 106, about 107, about 108, about 109, about 1010, about 1011, about 1012, about 1013 or more bacterial cells or CFUs in total for all of the bacterial strains combined per dosage amount. As discussed above, bacteria of each of the bacterial strains may be present in different amounts. In some embodiments, the compositions, including pharmaceutical compositions, contain about 10−7, about 10−6, about 10−5, about 10−4, about 10−3, about 10−2, about 10−1 or more grams of bacteria (bacterial cells or CFU) of each of the bacterial strains in the composition per dosage amount. In some embodiments, the compositions, including pharmaceutical compositions, contain about 10−7, about 10−6, about 10−5, about 10−4, about 10−3, about 10−2, about 10−1 or more grams of bacteria (bacterial cells or CFU) in total for all of the bacterial strains combined per dosage amount.


In some embodiments, the dosage amount is one administration device (e.g., one table, pill or capsule). In some embodiments, the dosage amount is the amount administered at one time, which may be in the form of more than one administration device (e.g., more than one table, pill or capsule). In some embodiment, the dosage amount is the amount that is administered in a particular period (e.g., one day or one week).


As described herein, any of the pharmaceutical compositions described herein may be administered once, as a single dose. In some embodiments, the pharmaceutical compositions described herein are administered in multiple doses. In some embodiments, each dose is administered in the form of one or more capsules. In some embodiments, each dose comprises administration of multiple capsules. In some embodiments, each dose is administered in the form of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more capsules.


In some embodiments, each capsule contains between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 bacterial cells or CFU of each of the bacterial strains per capsule.


In some embodiments, each capsule contains between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 total bacterial cells or CFU per capsule. In some embodiments, each capsule contains between 107 and 109, between 107 and 108, or between 108 and 109 total bacteria. In some embodiments, each capsule contains about 1.0×107, 2.0×107, 3.0×107, 4.0×107, 5.0×107, 6.0×107, 7.0×107, 8.0×107, 9.0×107, 1.0×108, 2.0×108, 3.0×108, 4.0×108, 5.0×108, 6.0×108, 7.0×108, 8.0×108, 9.0×108, 1.0×109, 1.1×109, 1.2×109, 1.3×109, 1.4×109, 1.5×109, 1.6×109, 1.7×109, 1.8×109, 1.9×109, 2.0×109, 2.1×109, 2.2×109, 2.3×109, 2.4×109, 2.5×109, 2.6×109, 2.7×109, 2.8×109, 2.9×109, 3.0×109, 3.1×109, 3.2×109, 3.3×109, 3.4×109, 3.5×109, 3.6×109, 3.7×109, 3.8×109, 3.9×109, 4.0×109, 4.1×109, 4.2×109, 4.3×109, 4.4×109, 4.5×109, 4.6×109, 4.7×109, 4.8×109, 4.9×109, 5.0×109 total bacterial cells or CFU.


In some embodiments, each capsule contains between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 bacterial cells or CFU of each bacterial strain per capsule.


In some embodiments, the pharmaceutical compositions contain between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 bacterial cells or CFUs of each of the bacterial strains per dosage amount. In some embodiments, the pharmaceutical compositions contain between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 total bacterial cells or CFUs per dosage amount.


In some embodiments, the compositions disclosed herein contain between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 total bacteria or colony forming units per milliliter.


In some embodiments, the compositions disclosed herein contain between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 bacterial cells or colony forming units of bacteria. In some embodiments, the compositions disclosed herein contain between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 bacterial cells or colony forming units of bacteria per milliliter.


In some embodiments, a composition that includes more than one bacterial strain may contain each bacterial strain in the same quantities, in terms of bacterial cells or CFUs. For example, a composition of the invention comprising Collinsella aerofaciens and Bifidobacterium longum may comprise 1×108 CFU of Collinsella aerofaciens and 1×108 CFU of Bifidobacterium longum per milliliter or may comprise 1×108 Collinsella aerofaciens cells and 1×108 Bifidobacterium longum cells per milliliter.


In some embodiments, the pharmaceutical composition comprises at least 1.6×109 total CFUs. In some embodiments, the pharmaceutical composition comprises at least 1.6×109 total CFUs and is administered as a single dose. In some embodiments, the pharmaceutical composition comprises at least 1.6×109 total CFUs and is administered as multiple (e.g., 2, 3, 4, 5, or more) doses. In some embodiments, the pharmaceutical composition comprises at least 1.6×109 total CFUs and is administered as two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or more doses. In some embodiments, each of the multiple doses are administered at regular intervals. In some embodiments, each of the multiple doses are on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.).


In some embodiments, the pharmaceutical composition comprises at least 4.0×109 total CFUs. In some embodiments, the pharmaceutical composition comprises at least 4.0×109 total CFUs and is administered as a single dose. In some embodiments, the pharmaceutical composition comprises at least 4.0×109 total CFUs and is administered as multiple (e.g., 2, 3, 4, 5, or more) doses. In some embodiments, the pharmaceutical composition comprises at least 4.0×1010 total CFUs and is administered as two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or more doses. In some embodiments, each of the multiple doses are administered at regular intervals. In some embodiments, each of the multiple doses are on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.).


In some embodiments, the pharmaceutical composition comprises at least 8.0×109 total CFUs. In some embodiments, the pharmaceutical composition comprises at least 8.0×109 total CFUs and is administered as a single dose. In some embodiments, the pharmaceutical composition comprises at least 8.0×109 total CFUs and is administered as multiple (e.g., 2, 3, 4, 5, or more) doses. In some embodiments, the pharmaceutical composition comprises at least 8.0×109 total CFUs and is administered as two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or more doses. In some embodiments, each of the multiple doses are administered at regular intervals. In some embodiments, each of the multiple doses are on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.).


In some embodiments, the pharmaceutical composition comprises at least 2.8×1010 total CFUs. In some embodiments, the pharmaceutical composition comprises at least 2.8×1010 total CFUs and is administered as a single dose. In some embodiments, the pharmaceutical composition comprises at least 2.8×1010 total CFUs and is administered as multiple (e.g., 2, 3, 4, 5, or more) doses. In some embodiments, the pharmaceutical composition comprises at least 2.8×1010 total CFUs and is administered as two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or more doses. In some embodiments, the pharmaceutical composition comprises at least 2.8×1010 total CFUs and is administered as seven doses. In some embodiments, each of the multiple doses are administered at regular intervals. In some embodiments, each of the multiple doses are on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.).


In some embodiments, the pharmaceutical composition comprises at least 4.0×1010 total CFUs. In some embodiments, the pharmaceutical composition comprises at least 4.0×1010 total CFUs and is administered as a single dose. In some embodiments, the pharmaceutical composition comprises at least 4.0×1010 total CFUs and is administered as multiple (e.g., 2, 3, 4, 5, or more) doses. In some embodiments, the pharmaceutical composition comprises at least 4.0×1010 total CFUs and is administered as two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or more doses. In some embodiments, the pharmaceutical composition comprises at least 4.0×1010 total CFUs and is administered as five doses. In some embodiments, each of the multiple doses are administered at regular intervals. In some embodiments, each of the multiple doses are on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.). In some embodiments, the pharmaceutical composition comprises at least 4.0×1010 total CFUs and is administered as five doses, each of which are administered on five consecutive days.


In some embodiments, the pharmaceutical composition comprises at least 5.6×1010 total CFUs. In some embodiments, the pharmaceutical composition comprises at least 5.6×1010 total CFUs and is administered as a single dose. In some embodiments, the pharmaceutical composition comprises at least 5.6×1010 total CFUs and is administered as multiple (e.g., 2, 3, 4, 5, or more) doses. In some embodiments, the pharmaceutical composition comprises at least 5.6×1010 total CFUs and is administered as two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or more doses. In some embodiments, the pharmaceutical composition comprises at least 5.6×1010 total CFUs and is administered as fourteen doses. In some embodiments, each of the multiple doses are administered at regular intervals. In some embodiments, each of the multiple doses are on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.). In some embodiments, the pharmaceutical composition comprises at least 5.6×1010 total CFUs and is administered as fourteen doses, each of which are administered on fourteen consecutive days.


In some embodiments, the pharmaceutical composition comprises at least 1.1×1011 total CFUs. In some embodiments, the pharmaceutical composition comprises at least 1.1×1011 total CFUs and is administered as a single dose. In some embodiments, the pharmaceutical composition comprises at least 1.1×1011 total CFUs and is administered as multiple (e.g., 2, 3, 4, 5, or more) doses. In some embodiments, the pharmaceutical composition comprises at least 1.1×1011 total CFUs and is administered as two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or more doses. In some embodiments, the pharmaceutical composition comprises at least 1.1×1011 total CFUs and is administered as fourteen doses. In some embodiments, each of the multiple doses are administered at regular intervals. In some embodiments, each of the multiple doses are on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.). In some embodiments, the pharmaceutical composition comprises at least 1.1×1011 total CFUs and is administered as fourteen doses, each of which are administered on fourteen consecutive days.


In some embodiments, the pharmaceutical composition comprises at least 2.1×1010 total CFUs. In some embodiments, the pharmaceutical composition comprises at least 2.1×1010 total CFUs and is administered as a single dose. In some embodiments, the pharmaceutical composition comprises at least 2.1×1010 total CFUs and is administered as multiple (e.g., 2, 3, 4, 5, or more) doses. In some embodiments, the pharmaceutical composition comprises at least 2.1×1010 total CFUs and is administered as two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or more doses. In some embodiments, the pharmaceutical composition comprises at least 2.1×1010 total CFUs and is administered as five doses. In some embodiments, each of the multiple doses are administered at regular intervals. In some embodiments, each of the multiple doses are on consecutive days (e.g., first dose on day 1, second dose of day 2, third dose on day 3, etc.). In some embodiments, the pharmaceutical composition comprises at least 2.1×1010 total CFUs and is administered as five doses, each of which are administered on five consecutive days.


As described herein, any of the pharmaceutical compositions described herein may be administered to a subject in one dose or in multiple doses (e.g., initial administration), which may be followed by one or more additional doses of any of the pharmaceutical compositions described herein. In some embodiments, any of pharmaceutical composition described herein may be administered to a subject in one dose or in multiple doses in an initial administration, followed by one or more additional doses of a pharmaceutical composition comprising the same one or more bacterial strains as the pharmaceutical composition of the initial administration. In some embodiments, any of pharmaceutical composition described herein may be administered to a subject in one dose or in multiple doses in an initial administration, followed by one or more additional doses of a pharmaceutical composition comprising more total bacteria (colony-forming units) relative to the initial administration of the pharmaceutical composition. In some embodiments, any of pharmaceutical composition described herein may be administered to a subject in one dose or in multiple doses in an initial administration, followed by one or more additional doses of a pharmaceutical composition comprising fewer total bacteria (colony-forming units) relative to the initial administration of the pharmaceutical composition. In some embodiments, the initial administration includes at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses of any of the pharmaceutical compositions described herein. In some embodiments, the additional administration includes at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses of any of the pharmaceutical compositions described herein. In some embodiments, the initial administration comprises two doses of any of the pharmaceutical composition and the additional administration comprises three doses of any of the pharmaceutical compositions described herein.


In some embodiments, any of pharmaceutical composition described herein may be administered to a subject in one dose or in multiple doses in an initial administration, followed by one or more additional doses of a pharmaceutical composition comprising fewer total bacteria (colony-forming units) relative to the initial administration of the pharmaceutical composition. In such embodiments, the dose(s) of the initial administration may be referred to as a “high dose” and the dose(s) of the additional administration may be referred to as a “low dose. In some embodiments, the high dose is at least 1.1-fold, 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 11-fold, 12-fold, 13-fold, 14-fold, 15-fold, 16-fold, 17-fold, 18-fold, 19-fold, 20-fold or more higher than the low dose. In some embodiments, the high dose is 8.0×109 CFUs. In some embodiments, the low dose is 1.6×109 CFUs. In some embodiments, the initial administration comprises multiple doses (e.g., 2, 3, 4, 5 or more) of 8.0×109 CFUs and the additional administration comprises multiple doses (e.g., 2, 3, 4, 5 or more) of 1.6×109 CFUs. In some embodiments, the low dose is 1.6×109 CFUs. In some embodiments, the initial administration comprises two doses of 8.0×109 CFUs and the additional administration comprises three doses of 1.6×109 CFUs.


In some embodiments, the one or more additional administrations is performed on the day following the initial administration (e.g., consecutive days). In some embodiments, the one or more additional administrations is performed at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks or longer following the initial administration. In some embodiments, the one or more additional administrations is performed at least 6 weeks after the initial administration. In some embodiments, the one or more additional administrations is performed at least 12 weeks after the initial administration.


In some embodiments, the compositions, including pharmaceutical compositions, contain between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 bacterial cells or CFUs of each of the bacterial strains per dosage amount. In some embodiments, the compositions, including pharmaceutical compositions contain between 10 and 1013, between 102 and 1013, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 1010 and 1013, between 1011 and 1013, between 1012 and 1013, between 10 and 1012, between 102 and 1012, between 103 and 1012, between 104 and 1012, between 105 and 1012, between 106 and 1012, between 107 and 1012, between 108 and 1012, between 109 and 1012, between 1010 and 1012, between 1011 and 1012, between 10 and 1011, between 102 and 1011, between 103 and 1013, between 104 and 1013, between 105 and 1013, between 106 and 1013, between 107 and 1011, between 108 and 1011, between 109 and 1011, between 1010 and 1011, between 10 and 1010, between 102 and 1010, between 103 and 1010, between 104 and 1010, between 105 and 1010, between 106 and 1010, between 107 and 1010, between 108 and 1010, between 109 and 1010, between 10 and 109, between 102 and 109, between 103 and 109, between 104 and 109, between 105 and 109, between 106 and 109, between 107 and 109, between 108 and 109, between 10 and 108, between 102 and 108, between 103 and 108, between 104 and 108, between 105 and 108, between 106 and 108, between 107 and 108, between 10 and 107, between 102 and 107, between 103 and 107, between 104 and 107, between 105 and 107, between 106 and 107, between 10 and 106, between 102 and 106, between 103 and 106, between 104 and 106, between 105 and 106, between 10 and 105, between 102 and 105, between 103 and 105, between 104 and 105, between 10 and 104, between 102 and 104, between 103 and 104, between 10 and 103, between 102 and 103, or between 10 and 102 total bacterial cells or CFUs per dosage amount.


In some embodiments, the compositions, including pharmaceutical compositions, contain between 10−7 and 10−1, between 10−6 and 10−1, between 105 and 10−1, between 10−4 and 10−1, between 10−3 and 10−1, between 10−2 and 10−1, between 10−7 and 10−2, between 10−6 and 10−2, between 105 and 10−2, between 10−4 and 10−2, between 10−3 and 10−2, between 10−7 and 10−3, between 10−6 and 10−3, between 105 and 10−3, between 10−4 and 10−3, between 10−7 and 10−4, between 10−6 and 10−4, between 10−5 and 10−4, between 10−7 and 10−5, between 10−6 and 105, or between 10−7 and 106 grams of bacteria of each of the bacterial strains in the composition per dosage amount. In some embodiments, the compositions, including pharmaceutical compositions, disclosed herein contain between 10−7 and 10−1, between 10−6 and 10−1, between 105 and 10−1, between 10−4 and 10−1, between 10−3 and 10−1, between 10−2 and 10−1, between 10−7 and 10−2, between 10−6 and 10−2, between 10−5 and 10−2, between 10−4 and 10−2, between 10−3 and 10−2, between 10−7 and 10−3, between 106 and 10−3, between 10−5 and 10−3, between 10−4 and 10−3, between 10−7 and 10−4, between 106 and 104, between 10−5 and 104, between 10−7 and 105, between 10−6 and 105, or between 10−7 and 10−6 grams of all of the bacteria combined (total) per dosage amount.


Aspects of the present disclosure also provide food products comprising any of the compositions described herein and a nutrient. Also with the scope of the present disclosure are food products comprising any of the bacterial strains described herein and a nutrient. In some embodiments, the food product may further comprise taurine. Food products are, in general, intended for the consumption of a human or an animal. Any of the bacterial strains described herein may be formulated as a food product. In some embodiments, the bacterial strains are formulated as a food product in spore form. In some embodiments, the bacterial strains are formulated as a food product in vegetative form. In some embodiments, the food product comprises both vegetative bacteria and bacteria in spore form. The compositions disclosed herein can be used in a food or beverage, such as a health food or beverage, a food or beverage for infants, a food or beverage for pregnant women, athletes, senior citizens or other specified group, a functional food, a beverage, a food or beverage for specified health use, a dietary supplement, a food or beverage for patients, or an animal feed.


Non-limiting examples of the foods and beverages include various beverages such as juices, refreshing beverages, tea beverages, drink preparations, jelly beverages, and functional beverages; alcoholic beverages such as beers; carbohydrate-containing foods such as rice food products, noodles, breads, and pastas; paste products such as fish hams, sausages, paste products of seafood; retort pouch products such as curries, food dressed with a thick starchy sauces, soups; dairy products such as milk, dairy beverages, ice creams, cheeses, and yogurts; fermented products such as fermented soybean pastes, yogurts, fermented beverages, and pickles; bean products; various confectionery products such as Western confectionery products including biscuits, cookies, and the like, Japanese confectionery products including steamed bean-jam buns, soft adzuki-bean jellies, and the like, candies, chewing gums, gummies, cold desserts including jellies, cream caramels, and frozen desserts; instant foods such as instant soups and instant soy-bean soups; microwavable foods; and the like. Further, the examples also include health foods and beverages prepared in the forms of powders, granules, tablets, capsules, liquids, pastes, and jellies.


Food products containing bacterial strains described herein may be produced using methods known in the art and may contain the same amount of bacteria (e.g., by weight, amount or CFU) as the pharmaceutical compositions provided herein. Selection of an appropriate amount of bacteria in the food product may depend on various factors, including for example, the serving size of the food product, the frequency of consumption of the food product, the specific bacterial strains contained in the food product, the amount of water in the food product, and/or additional conditions for survival of the bacteria in the food product.


Examples of food products which may be formulated to contain any of the bacterial strains described herein include, without limitation, a beverage, a drink, a bar, a snack, a dairy product, a confectionery product, a cereal product, a ready-to-eat product, a nutritional formula, such as a nutritional supplementary formulation, a food or beverage additive.









TABLE 1







Examples of bacterial species of the


bacterial strains disclosed herein










47-mix (Closely related

SEQ



species based on 16S
Additional closely related
ID


sequence)
species
NO:
Strain














Collinsella aerofaciens_F


Collinsella aerofaciens

1
1



Bacteroides xylanisolvens


2
2



Alistipes putredinis


3
3



Alistipes shahii


4
4



Eubacterium_E hallii


Eubacterium hallii

5
5



Blautia_A obeum


Blautia obeum

6
6



Odoribacter splanchnicus


7
7



Bacteroides cellulosilyticus


8
8



Bacteroides uniformis


9
9



Bacteroides_B vulgatus


Bacteroides vulgatus

10
10



Bacteroides fragilis


11
11



Bacteroides caccae


12
12



Paeniclostridium sordellii


Clostridium sordellii

13
13



Blautia producta


14
14



Absiella innocuum


Erysipelotrichaceae

15
15




bacterium




Clostridium_M


Clostridium clostridioforme

16
16



clostridioforme




Paraclostridium massiliensis


Clostridium bifermentans

17
17



Dorea longicatena B


Dorea longicatena

18
18



Bacteroides thetaiotaomicron


19
19



Parabacteroides distasonis


20
20



Escherichia coli


21
21



Bifidobacterium longum


22
22



Absiella innocuum


Clostridium innoccum

23
23



Fusobacterium_A sp


Fusobacterium mortiferum

24
24



Parabacteroides merdae


25
25



Coprococcus_B comes


Coprococcus comes

26
26



Agathobacter rectale


Eubacterium rectale

27
27



Erysipelatoclostridium


28
28



ramosum




Clostridium

M citroniae


Clostridium citroniae

29
29



Bacteroides faecis


30
30



Bacteroides ovatus


31
31



Bifidobacterium


32
32



pseudocatenulatum




Bacteroides caccae


33
33



Bifidobacterium adolescentis


34
34



Agathobaculum sp


Agathobaculum sp,

35
35


MUR_P3C8a

Agathobaculum





butyriciproducens




Phascolarctobacterium


Phascolarctobacterium

36
36



faecium MUR_P6E9


faecium




Akkermansia muciniphila


37
37



Barnesiella intestinihomins


38
38



Bilophila wadsworthia


39
39



Blautia faecis


40
40



Blautia wexlerae


41
41



Blautia luti


42
42



Butyricimonas synergistica


43
43



Clostridium bolteae


44
44



Parasutterella


45
45



excrementihominis




Prevotella copri


46
46



Ruminococcus faecis


47
47



















SEQUENCES















SEQ ID NO: 1 Collinsella aerofaciens_F Strain 1


AGAGTTCGATCCTGGCTCAGGATGAACGCTGGCGGCGCGCCTAACACATGCAAGT


CGAACGGCACCCCTCTCCGGAGGGAAGCGAGTGGCGAACGGCTGAGTAACACGTG


GAGAACCTGCCCCCTCCCCCGGGATAGCCGCCCGAAAGGACGGGTAATACCGGAT


ACCCCGGGGTGCCGCATGGCACCCCGGCTAAAGCCCCGACGGGAGGGGATGGCT


CCGCGGCCCATCAGGTAGACGGCGGGGTGACGGCCCACCGTGCCGACAACGGGT


AGCCGGGTTGAGAGACCGACCGGCCAGATTGGGACTGAGACACGGCCCAGACTCC


TACGGGAGGCAGCAGTGGGGAATCTTGCGCAATGGGGGGAACCCTGACGCAGCGA


CGCCGCGTGCGGGACGGAGGCCTTCGGGTCGTAAACCGCTTTCAGCAGGGAAGAG


TCAAGACTGTACCTGCAGAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGT


AATACGTAGGGGGCGAGCGTTATCCGGATTCATTGGGCGTAAAGCGCGCGTAGGC


GGCCCGGCAGGCCGGGGGTCGAAGCGGGGGGCTCAACCCCCCGAAGCCCCCGGA


ACCTCCGCGGCTTGGGTCCGGTAGGGGAGGGTGGAACACCCGGTGTAGCGGTGG


AATGCGCAGATATCGGGTGGAACACCGGTGGCGAAGGCGGCCCTCTGGGCCGAGA


CCGACGCTGAGGCGCGAAAGCTGGGGGAGCGAACAGGATTAGATACCCTGGTAGT


CCCAGCCGTAAACGATGGACGCTAGGTGTGGGGGGACGATCCCCCCGTGCCGCAG


CCAACGCATTAAGCGTCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAG


GAATTGACGGGGGCCCGCACAAGCAGCGGAGCATGTGGCTTAATTCGAAGCAACG


CGAAGAACCTTACCAGGGCTTGACATATGGGTGAAGCGGGGGAGACCCCGTGGCC


GAGAGGAGCCCATACAGGTGGTGCATGGCTGTCGTCAGCTCGTGTCGTGAGATGTT


GGGTTAAGTCCCGCAACGAGCGCAACCCCCGCCGCGTGTTGCCATCGGGTGATGC


CGGGAACCCACGCGGGACCGCCGCCGTCAAGGCGGAGGAGGGGGGGGACGACGT


CAAGTCATCATGCCCCTTATGCCCTGGGCTGCACACGTGCTACAATGGCCGGTACA


GAGGGATGCCACCCCGCGAGGGGGAGCGGATCCCGGAAAGCCGGCCCCAGTTCG


GATTGGGGGCTGCAACCCGCCCCCATGAAGTCGGAGTTGCTAGTAATCGCGGATC


AGCATGCCGCGGTGAATGCGTTCCCGGGCCTTGTACACACCGCCCGTCACACCAC


CCGAGTCGTCTGCACCCGAAGTCGCCGGCCCAACCGAGAGGGGGGAGGCGCCGA


AGGTGTGGAGGGTGAGGGGGGTGAAGTCGTAACAAGGTA





SEQ ID NO: 2 Bacteroides xylanisolvens Strain 2


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTC


GAGGGGCAGCATTTTAGTTTGCTTGCAAACTAAAGATGGCGACCGGCGCACGGGTG


AGTAACACGTATCCAACCTGCCGATAACTCGGGGATAGCCTTTCGAAAGAAAGATTA


ATATCCGATAGTATATTAAAACCGCATGGTTTTACTATTAAAGAATTTCGGTTATCGA


TGGGGATGCGTTCCATTAGTTTGTTGGCGGGGTAACGGCCCACCAAGACTACGATG


GATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACT


CCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGC


CAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATA


AAGTATTCCACGTGTGGGATTTTGTATGTACCATATGAATAAGGATCGGCTAACTCC


GTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTT


TAAAGGGAGCGTAGGTGGATTGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGT


AAAATTGCAGTTGAAACTGGCAGTCTTGAGTACAGTAGAGGTGGGCGGAATTCGTG


GTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCA


CTAGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATA


CCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGC


GGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAA


CTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGAT


GATACGCGAGGAACCTTACCCGGGCTTAAATTGCATTTGAATAATCTGGAAACAGGT


TAGCCGCAAGGCAAATGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAG


GTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTTA


TGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGAC


GTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTA


CAGAAGGCAGCTACCTGGCGACAGGATGCTAATCCCAAAAACCTCTCTCAGTTCGG


ATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAG


CCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATG


AAAGCCGGGGGTACCTGAAGTACGTAACCGCAAGGAGCGTCCTAGGGTAAAACTG


GTAATTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAACA


CCT





SEQ ID NO: 3 Alistipes putredinis Strain 3


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGGCAGGCTTAACACATGCAAGTC


GAGGGGCAGCATAATGGATAGCAATATCTATGGTGGCGACCGGCGCACGGGTGCG


TAACGCGTATGCAACCTACCTTTAACAGGGGGATAACACTGAGAAATTGGTACTAAT


ACCCCATAATATCATAGAAGGCATCTTTTATGGTTGAAAATTCCGATGGTTAGAGAT


GGGCATGCGTTGTATTAGCTAGTTGGTGGGGTAACGGCTCACCAAGGCGACGATAC


ATAGGGGGACTGAGAGGTTAACCCCCCACACTGGTACTGAGACACGGACCAGACT


CCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGCAAGTCTGAACCAGC


CATGCCGCGTGCAGGATGACGGCTCTATGAGTTGTAAACTGCTTTTGTACGAGGGT


AAACGCAGATACGTGTATCTGTCTGAAAGTATCGTACGAATAAGGATCGGCTAACTC


CGTGCCAGCAGCCGCGGTAATACGGAGGATTCAAGCGTTATCCGGATTTATTGGGT


TTAAAGGGTGCGTAGGCGGTTTGATAAGTTAGAGGTGAAATTTCGGGGCTCAACCC


TGAACGTGCCTCTAATACTGTTGAGCTAGAGAGTAGTTGCGGTAGGCGGAATGTAT


GGTGTAGCGGTGAAATGCTTAGAGATCATACAGAACACCGATTGCGAAGGCAGCTT


ACCAAACTATATCTGACGTTGAGGCACGAAAGCGTGGGGAGCAAACAGGATTAGAT


ACCCTGGTAGTCCACGCAGTAAACGATGATAACTCGTTGTCGGCGATACACAGTCG


GTGACTAAGCGAAAGCGATAAGTTATCCACCTGGGGAGTACGTTCGCAAGAATGAA


ACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGA


TGATACGCGAGGAACCTTACCCGGGCTTGAAAGTTAGCGACGATTCTTGAAAGAGG


ATTTCCCTTCGGGGCGCGAAACTAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGT


GAGGTGTCGGGTTAAGTCCCATAACGAGCGCAACCCCTACCGTTAGTTGCCATCAG


GTGAAGCTGGGCACTCTGGGGGGACTGCCGGTGTAAGCCGAGAGGAAGGTGGGG


ATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGT


AGGTACAGAGGGCAGCTACCCAGCGATGGGATGCGAATCTCGAAAGCCTATCTCAG


TTCGGATTGGAGGCTGAAACCCGCCTCCATGAAGTTGGATTCGCTAGTAATCGCGC


ATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAG


CCATGGGAGCCGGGGGTGCCTGAAGTTCGTGACCGCAAGGAGCGACCTAGGGCAA


AACTGGTGACTGGGGCTAAGTCGTAACAAGGTA





SEQ ID NO: 4 Alistipes shahii Strain 4


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGGCAGGCCTAACACATGCAAGTC


GAGGGGCAGCACGGTGTAGCAATACACTGGTGGCGACCGGCGCACGGGTGCGTAA


CGCGTATGCAACCTACCCATAACAGGGGGATAACACTGAGAAATTGGTACTAATAC


CCCATAACATCAGGACCGGCATCGGTTCTGGTTGAAAACTCCGGTGGTTATGGATG


GGCATGCGTTGTATTAGCTGGTTGGTGAGGTAACGGCTCACCAAGGCAACGATACA


TAGGGGGACTGAGAGGTTAACCCCCCACATTGGTACTGAGACACGGACCAAACTCC


TACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGCAAGTCTGAACCAGCCAT


GCCGCGTGCAGGAAGACGGCTCTATGAGTTGTAAACTGCTTTTGTACGAGAGTAAA


CGCTCTTACGTGTAAGAGCCTGAAAGTATCGTACGAATAAGGATCGGCTAACTCCG


TGCCAGCAGCCGCGGTAATACGGAGGATCCAAGCGTTATCCGGATTTATTGGGTTT


AAAGGGTGCGTAGGCGGTTTGATAAGTTAGAGGTGAAATACCGGTGCTTAACACCG


GAACTGCCTCTAATACTGTTGAACTAGAGAGTAGTTGCGGTAGGCGGAATGTATGG


TGTAGCGGTGAAATGCTTAGAGATCATACAGAACACCGATTGCGAAGGCAGCTTAC


CAAACTATATCTGACGTTGAGGCACGAAAGCGTGGGGAGCAAACAGGATTAGATAC


CCTGGTAGTCCACGCAGTAAACGATGATAACTCGCTGTCGGCGATACACAGTCGGC


GGCTAAGCGAAAGCGATAAGTTATCCACCTGGGGAGTACGTTCGCAAGAATGAAAC


TCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATG


ATACGCGAGGAACCTTACCCGGGCTTGAAAGTTACTGACGATTCTGGAAACAGGAT


TTCCCTTCGGGGCAGGAAACTAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGA


GGTGTCGGGTTAAGTCCCATAACGAGCGCAACCCCTACCGTTAGTTGCCATCAGGT


CAAGCTGGGCACTCTGGGGGGACTGCCGGTGTAAGCCGAGAGGAAGGTGGGGATG


ACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGTAGG


TACAGAGGGCAGCTACCCAGTGATGGGATGCGAATCTCGAAAGCCTATCTCAGTTC


GGATCGGAGGCTGAAACCCGCCTCCGTGAAGTTGGATTCGCTAGTAATCGCGCATC


AGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCA


TGGAAGCTGGGGGTGCCTGAAGTTCGTGACCGCAAGGAGCGACCTAGGGCAAAAC


CGGTGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAA


CACCT





SEQ ID NO: 5 Eubacterium_E hallii Strain 5


CTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATTCC


AGTTTGCTTGCAAACTGGAGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCA


ACCTGCCGATAACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGCAT


AATAGAACCGCATGGTTTGATTATTAAAGAATTTCGGTTATCGATGGGGATGCGTTC


CATTAGGCAGTTGGTGGGGTAACGGCCCACCAAACCTTCGATGGATAGGGGTTCTG


AGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGC


AGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAA


GGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGTGGTCCACGT


GTGGATTTTTGTATGTACCATATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCG


CGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTA


GGTGGACAGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTG


ATACTGGCTGTCTTGAGTACAGTAGAGGGGGGGGGAATTCGTGGTGTAGCGGTGAA


ATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGACTGCAACT


GACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCA


CACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAAA


GCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTG


ACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGA


ACCTTACCCGGGCTTAAATTGCATTTGAATATATTGGAAACAGTATAGTCGTAAGAC


AAATGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAA


GTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCATGCTGAGGACTC


TGGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCA


CGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCCGC


TACCTGGTGACAGGATGCTAATCCCAAAAGCCTCTCTCAGTTCGGATCGAAGTCTG


CAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGG


TGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGG


TACCTGAAGTACGTAACCGCAAGGAGCGTCCTAGGGTAAAACTGGTAATTGGGGCT


AAGTCGTAACAAGGTA





SEQ ID NO: 6 Blautia_A obeum Strain 6


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGGGGCGTGCTTAACACATGCAAGTC


GAACGGGAAACCTTTTATTGAAGCTTCGGCAGATTTAGCTGGTTTCTAGTGGCGGA


CGGGTGAGTAACGCGTGGGTAACCTGCCTTATACAGGGGGATAACAACCAGAAATG


GTTGCTAATACCGCATAAGCGCACAGGACCGCATGGTCCGGTGTGAAAAACTCCGG


TGGTATAAGATGGACCCGCGTTGGATTAGCTAGTTGGCAGGGTAACGGCCTACCAA


GGCGACGATCCATAGCCGGCCTGAGAGGGTGAACGGCCACATTGGGACTGAGACA


CGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAAC


CCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGTAAACTTCTATC


AGCAGGGAAGATAGTGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCA


GCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAG


GGAGCGTAGACGGACTGGCAAGTCTGATGTGAAAGGCGGGGGCTCAACCCCTGGA


CTGCATTGGAAACTGTTAGTCTTGAGTGCCGGAGAGGTAAGCGGAATTCCTAGTGT


AGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTG


GACGGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACC


CTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTTGGGGAGCAAAGCTCTTCG


GTGCCGCCGCAAACGCATTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAA


ACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGA


AGCAACGCGAAGAACCTTACCAAGTCTTGACATCCCTCTGACCGTTCCTTAACCGG


AACTTTCCTTCGGGACAGGGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTC


GTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATCCCCAGTAGCCAGC


AGTCCGGCTGGGCACTCTGAGGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGG


ATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGGCG


TAAACAAAGGGAAGCA-


AGCCTGCGAAGGTAAGCAAATCCCAAAAATAACGTCCCAGTTCGGACTGCAGTCTG


CAACTCGACTGCACGAAGCTGGAATCGCTAGTAATCGCGGATCAGAATGCCGCGGT


GAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACG


CCCGAAGTCAGTGACCTAACTGCAAAGAAGGAGCTGCCGAAGGGGGGACCGATGA


CTGGGGTGAAGTCGTAACAAGGTA





SEQ ID NO: 7 Odoribacter splanchnicus Strain 7


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCTTAACACATGCAAGTC


GAGGGGCATCATGAGGTAGCAATACCTTGATGGCGACCGGCGCACGGGTGAGTAA


CGCGTATGCAACCTGCCTGATACCGGGGTATAGCCCATGGAAACGTGGATTAACAC


CCCATAGTACTTTTATCCTGCATGGGATGTGAGTTAAATGTTTAAGGTATCGGATGG


GCATGCGTCCTATTAGTTAGTTGGGGGGGTAACAGCCCACCAAGACGATGATAGGT


AGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCT


ACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAA


GTCGCGTGAGGGAAGACTGCCCTATGGGTTGTAAACCTCTTTTATAAGGGAAGAAT


AAGTTCTACGTGTAGAATGATGCCTGTACCTTATGAATAAGCATCGGCTAACTCCGT


GCCAGCAGCCGCGGTAATACGGAGGATGCGAGCGTTATCCGGATTTATTGGGTTTA


AAGGGTGCGTAGGCGGTTTATTAAGTTAGTGGTTAAATATTTGAGCTAAACTCAATT


GTGCCATTAATACTGGTAAACTGGAGTACAGACGAGGTAGGCGGAATAAGTTAAGT


AGCGGTGAAATGCATAGATATAACTTAGAACTCCGATAGCGAAGGCAGCTTACCAG


ACTGTAACTGACGCTGATGCACGAGAGCGTGGGTAGCGAACAGGATTAGATACCCT


GGTAGTCCACGCCGTAAACGATGCTCACTGGTTCTGTGCGATATATTGTACGGGAT


TAAGCGAAAGTATTAAGTGAGCCACCTGGGGAGTACGTCGGCAACGATGAAACTCA


AAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATA


CGCGAGGAACCTTACCTGGGTTTAAATGGGAAATGTCGTATTTGGAAACAGATATTC


TCTTCGGAGCGTTTTTCAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGT


GTCGGGTTAAGTCCCATAACGAGCGCAACCCTTACCGTTAGTTGCTAGCATGTAAT


GATGAGCACTCTAACGGGACTGCCACCGTAAGGTGAGAGGAAGGCGGGGATGACG


TCAAATCAGCACGGCCCTTACACCCAGGGCTACACACGTGTTACAATGGCCGGTAC


AGAGGGCCGCTACCAGGTGACTGGATGCCAATCTCAAAAGCCGGTCGTAGTTCGG


ATTGGAGTCTGTAACCCGACTCCATGAAGTTGGATTCGCTAGTAATCGCGCATCAG


CCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATG


GAAGCCGGGGGTGCCTGAAGTCCGTAACCGCGAGGATCGGCCTAGGGCAAAACTG


GTAACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAACA


CCT





SEQ ID NO: 8 Bacteroides cellulosilyticus Strain 8


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTC


GAGGGGCAGCATGACCTAGCAATAGGTTGATGGCGACCGGCGCACGGGTGAGTAA


CACGTATCCAACCTACCGGTTATTCCGGGATAGCCTTTCGAAAGAAAGATTAATACC


GGATAGTATAACGAGAAGGCATCTTTTTGTTATTAAAGAATTTCGATAACCGATGGG


GATGCGTTCCATTAGTTTGTTGGCGGGGTAACGGCCCACCAAGACATCGATGGATA


GGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTA


CGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAG


TAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGT


GAGCCACGTGTGGCTTTTTGTATGTACCATACGAATAAGGATCGGCTAACTCCGTG


CCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAA


AGGGAGCGTAGGCGGACTATTAAGTCAGCTGTGAAAGTTTGCGGCTCAACCGTAAA


ATTGCAGTTGATACTGGTCGTCTTGAGTGCAGTAGAGGTAGGCGGAATTCGTGGTG


TAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTTACTG


GACTGTAACTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCC


TGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACGGCAAGCGG


CCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTC


AAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGAT


ACGCGAGGAACCTTACCCGGGCTTAAATTGCAAATGAATATAGTGGAAACATTATAG


CCGCAAGGCATTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTG


TCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCATGC


TGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTC


AAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAG


AAGGCAGCTACACAGCGATGTGATGCTAATCCCAAAAGCCTCTCTCAGTTCGGATT


GGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCA


CGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAA


GCCGGGGGTACCTGAAGTCCGTAACCGTAAGGAGCGGCCTAGGGTAAAACTGGTA


ATTGGGGCTAAGTCGTA





SEQ ID NO: 9 Bacteroides uniformis Strain 9


CTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCA


TGAACTTAGCTTGCTAAGTTTGATGGCGACCGGCGCACGGGTGAGTAACACGTATC


CAACCTGCCGATGACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGC


ATAGTTCTTCCGCATGGTAGAACTATTAAAGAATTTCGGTCATCGATGGGGATGCGT


TCCATTAGGTTGTTGGCGGGGTAACGGCCCACCAAGCCTTCGATGGATAGGGGTTC


TGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAG


GCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTG


AAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATACGGGAATAAAGTGAGGCAC


GTGTGCCTTTTTGTATGTACCGTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGC


CGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCG


TAGGCGGACGCTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGT


TGATACTGGGTGTCTTGAGTACAGTAGAGGCAGGCGGAATTCGTGGTGTAGCGGTG


AAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTTGCTGGACTGTAA


CTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTC


CACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGA


AAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAAT


TGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAG


GAACCTTACCCGGGCTTGAATTGCAACTGAATGATGTGGAGACATGTCAGCCGCAA


GGCAGTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGC


TTAAGTGCCATAACGAGCGCAACCCTTATCGATAGTTACCATCAGGTTATGCTGGG


GACTCTGTCGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATC


AGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGG


CAGCTACACGGCGACGTGATGCTAATCCCTAAAGCCTCTCTCAGTTCGGATTGGAG


TCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGC


GCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCG


GGGGTACCTGAAGTGCGTAACCGCGAGGAGCGCCCTAGGGTAAAACTGGTGATTG


GGGCTAAGTCGTAACAAGGTA





SEQ ID NO: 10 Bacteroides_B vulgatus Strain 10


ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCA


AGTCGAGGGGCAGCATGGTCTTAGCTTGCTAAGGCCGATGGCGACCGGCGCACGG


GTGAGTAACACGTATCCAACCTGCCGTCTACTCTTGGACAGCCTTCTGAAAGGAAG


ATTAATACAAGATGGCATCATGAGTCCGCATGTTCACATGATTAAAGGTATTCCGGT


AGACGATGGGGATGCGTTCCATTAGATAGTAGGCGGGGTAACGGCCCACCTAGTCT


TCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTC


CAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGAGAGCCTGA


ACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATAAA


GGAATAAAGTCGGGTATGGATACCCGTTTGCATGTACTTTATGAATAAGGATCGGCT


AACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTAT


TGGGTTTAAAGGGAGCGTAGATGGATGTTTAAGTCAGTTGTGAAAGTTTGCGGCTC


AACCGTAAAATTGCAGTTGATACTGGATATCTTGAGTGCAGTTGAGGCAGGCGGAA


TTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGC


AGCCTGCTAAGCTGCAACTGACATTGAGGCTCGAAAGTGTGGGTATCAAACAGGAT


TAGATACCCTGGTAGTCCACACGGTAAACGATGAATACTCGCTGTTTGCGATATACA


GCAAGCGGCCAAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACG


GTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAA


TTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAGATGAATTACGGTGA


AAGCCGTAAGCCGCAAGGCATCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTG


CCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTGTTGTCAGTTACTA


ACAGGTTCCGCTGAGGACTCTGACAAGACTGCCATCGTAAGATGTGAGGAAGGTGG


GGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATG


GGGGGTACAGAGGGCCGCTACCACGCGAGTGGATGCCAATCCCAAAAACCTCTCT


CAGTTCGGACTGGAGTCTGCAACCCGACTCCACGAAGCTGGATTCGCTAGTAATCG


CGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTC


AAGCCATGGGAGCCGGGGGTACCTGAAGTGCGTAACCGCGAGGAGCGCCCTAGG


GTAAAACTGGTGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAG





SEQ ID NO: 11 Bacteroides fragilis Strain 11


ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCA


AGTCGAGGGGCATCAGGAAGAAAGCTTGCTTTCTTTGCTGGCGACCGGCGCACGG


GTGAGTAACACGTATCCAACCTGCCCTTTACTCGGGGATAGCCTTTCGAAAGAAAG


ATTAATACCCGATGGCATAATGATTCCGCATGGTTTCATTATTAAAGGATTCCGGTA


AAGGATGGGGATGCGTTCCATTAGGTTGTTGGTGAGGTAACGGCTCACCAAGCCTT


CGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTC


CAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGCTAGCCTGAA


CCAGCCAAGTAGCGTGAAGGATGAAGGCTCTATGGGTCGTAAACTTCTTTTATATAA


GAATAAAGTGCAGTATGTATACTGTTTTGTATGTATTATATGAATAAGGATCGGCTAA


CTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTG


GGTTTAAAGGGAGCGTAGGTGGACTGGTAAGTCAGTTGTGAAAGTTTGCGGCTCAA


CCGTAAAATTGCAGTTGATACTGTCAGTCTTGAGTACAGTAGAGGTGGGCGGAATT


CGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAG


CTCACTGGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTA


GATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGT


AAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGT


GAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATT


CGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAGTGGAATGATGTGGAAA


CATGTCAGTGAGCAATCACCGCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTG


CCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAA


CAGGTTATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGG


GGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATG


GGGGGTACAGAAGGCAGCTAGCGGGTGACCGTATGCTAATCCCAAAAGCCTCTCTC


AGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGC


GCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCA


AGCCATGGGAGCCGGGGGTACCTGAAGTACGTAACCGCAAGGATCGTCCTAGGGT


AAAACTGGTGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGC


TGGAACACCTCCTT





SEQ ID NO: 12 Bacteroides caccae Strain 12


TGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCATCAG


TTTGGTTTGCTTGCAAACCAAAGCTGGCGACCGGCGCACGGGTGAGTAACACGTAT


CCAACCTGCCTCATACTCGGGGATAGCCTTTCGAAAGAAAGATTAATATCCGATAGC


ATATATTTCCCGCATGGGTTTTATATTAAAGAAATTCGGTATGAGATGGGGATGCGT


TCCATTAGTTTGTTGGGGGGGTAACGGCCCACCAAGACTACGATGGATAGGGGTTC


TGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAG


GCAGCAGTGAGGAATATTGGTCAATGGACGCGAGTCTGAACCAGCCAAGTAGCGTG


AAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGTTGTCCAC


GTGTGGATTTTTGTATGTACCATATGAATAAGGATCGGCTAACTCCGTGCCAGCAGC


CGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCG


TAGGCGGATTGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTT


GATACTGGCAGTCTTGAGTGCAGTAGAGGTGGGCGGAATTCGTGGTGTAGCGGTG


AAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGAGTGTAA


CTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTC


CACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGA


AAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAAT


TGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAG


GAACCTTACCCGGGCTTAAATTGCAAATGAATTATGGGGAAACCCATAGGCCGCAA


GGCATTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCT


TAAGTGCCATAACGAGCGCAACCCTTATCTTCAGTTACTAACAGGTCATGCTGAGGA


CTCTGGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCA


GCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGC


CGCTACCTGGTGACAGGATGCCAATCCCAAAAACCTCTCTCAGTTCGGATCGAAGT


CTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCG


CGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGG


GGGTACCTGAAGTACGTAACCGCAAGGAGCGTCCTAGGGTAAAACTGGTAATTGGG


GCTAAGTCGTAACAAGGTA





SEQ ID NO: 13 Paeniclostridium sordellii Strain 13


GTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAG


CGAACCCTTCGGGGTGAGCGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCCT


GTACACACGGATAACATACCGAAAGGTATGCTAATACGGGATAATATATGAGAGTCG


CATGGCTTTTGTATCAAAGCTCTGGCGGTACAGGATGGACCCGCGTCTGATTAGCT


AGTTGGTAAGGTAACGGCTTACCAAGGCAACGATCAGTAGCCGACCTGAGAGGGTG


ATCGGCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGG


GGAATATTGCACAATGGGCGAAAGCCTGATGCAGCAACGCCGCGTGAGCGATGAA


GGCCTTCGGGTCGTAAAGCTCTGTCCTCAAGGAAGATAATGACGGTACTTGAGGAG


GAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCTAGCGT


TATCCGGAATTACTGGGCGTAAAGGGTGCGTAGGCGGTCTTTCAAGCCAGAAGTGA


AAGGCTACGGCTCAACCGTAGTAAGCTTTTGGAACTGTAGGACTTGAGTGCAGGAG


AGGAGAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACC


AGTAGCGAAGGCGGCTCTCTGGACTGTAACTGACGCTGAGGCACGAAAGCGTGGG


GAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAGTACTAGGT


GTCGGGGGTTACCCCCCTCGGTGCCGCAGCTAACGCATTAAGTACTCCGCCTGGG


AAGTACGCTCGCAAGAGTGAAACTCAAAGGAATTGACGGGGACCCGCACAAGTAGC


GGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCTAAGCTTGACATCC


CACTGACCTCTCCCTAATCGGAGATTTCCCTTCGGGGACAGTGGTGACAGGTGGTG


CATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGC


AACCCTTGCCTTTAGTTGCCAGCATTAAGTTGGGCACTCTAGAGGGACTGCCGAGG


ATAACTCGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGCTTAGGG


CTACACACGTGCTACAATGGGTGGTACAGAGGGTTGCCAAGCCGTGAGGTGGAGC


TAATCCCTTAAAGCCATTCTCAGTTCGGATTGTAGGCTGAAACTCGCCTACATGAAG


CTGGAGTTACTAGTAATCGCAGATCAGAATGCTGCGGTGAATGCGTTCCCGGGTCT


TGTACACACCGCCCGTCACACCATGGGAGTTGGGGGCGCCCGAAGCCGGTTAGCT


AACCTTTTAGGAAGCGGCCGTCGAAGGTGAAACCAATGACTGGGGTGAAGTCGTAA


CAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT





SEQ ID NO: 14 Blautia producta Strain 14


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTC


GAGCGAAGCACTAAGACAGATTTCTTCGGATTGAAGTCTTTGTGACTGAGCGGCGG


ACGGGTGAGTAACGCGTGGGTAACCTGCCTCATACAGGGGGATAACAGTTAGAAAT


GACTGCTAATACCGCATAAGCGCACAGGACCGCATGGTCTGGTGTGAAAAACTCCG


GTGGTATGAGATGGACCCGCGTCTGATTAGCTAGTTGGAGGGGTAACGGCCCACC


AAGGCGACGATCAGTAGCCGGCCTGAGAGGGTGAACGGCCACATTGGGACTGAGA


CACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAA


ACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGTAAACTTCTA


TCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCC


AGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAG


GGAGCGTAGACGGAAGAGCAAGTCTGATGTGAAAGGCTGGGGCTTAACCCCAGGA


CTGCATTGGAAACTGTTGTTCTAGAGTGCCGGAGAGGTAAGCGGAATTCCTAGTGT


AGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTG


GACGGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACC


CTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGGTGGCAAAGCCATTCG


GTGCCGCAGCAAACGCAATAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAA


ACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGA


AGCAACGCGAAGAACCTTACCAAGTCTTGACATCCCTCTGACCGTCCCGTAACGGG


GGCTTCCCTTCGGGGCAGAGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGT


CGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTAGTAGCCAG


CACATGATGGTGGGCACTCTAGGGAGACTGCCGGGGATAACCCGGAGGAAGGCGG


GGACGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATG


GCGTAAACAAAGGGAAGCGAGACAGCGATGTTGAGCGAATCCCAAAAATAACGTCC


CAGTTCGGACTGCAGTCTGCAACTCGACTGCACGAAGCTGGAATCGCTAGTAATCG


CGGATCAGAATGCCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCAC


ACCATGGGAGTCAGTAACGCCCGAAGTCAGTGACCTAACCGAAAGGAAGGAGCTG


CCGAAGGGGGGACCGATAACTGGGGTGAAGTCGTAACAAGGTA





SEQ ID NO: 15 Absiella innocuum Strain 15


ATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCATGCCTAATACATGCA


AGTCGAACGAAGT-


TTCGAGGAAGCTTGCTTCCAAAGAGACTTAGTGGCGAACGGGTGAGTAACACGTAG


GTAACCTGCCCATGTGTCCGGGATAACTGCTGGAAACGGTAGCTAAAACCGGATAG


GTATACAGAGCGCATGCTCAGTATATTAAAGCGCCCATCAAGGCGTGAACATGGAT


GGACCTGCGGCGCATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGATGATG


CGTAGCCGGCCTGAGAGGGTAAACGGCCACATTGGGACTGAGACACGGCCCAAAC


TCCTACGGGAGGCAGCAGTAGGGAATTTTCGTCAATGGGGGAAACCCTGAACGAG


CAATGCCGCGTGAGTGAAGAAGGTCTTCGGATCGTAAAGCTCTGTTGTAAGTGAAG


AACGGCTCATAGAGGAAATGCTATGGGAGTGACGGTAGCTTACCAGAAAGCCACGG


CTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGAATC


ATTGGGCGTAAAGGGTGCGTAGGTGGCGTACTAAGTCTGTAGTAAAAGGCAATGGC


TCAACCATTGTAAGCTATGGAAACTGGTATGCTGGAGTGCAGAAGAGGGCGATGGA


ATTCCATGTGTAGCGGTAAAATGCGTAGATATATGGAGGAACACCAGTGGCGAAGG


CGGTCGCCTGGTCTGTAACTGACACTGAGGCACGAAAGCGTGGGGAGCAAATAGG


ATTAGATACCCTAGTAGTCCACGCCGTAAACGATGAGAACTAAGTGTTGGAGGAATT


CAGTGCTGCAGTTAACGCAATAAGTTCTCCGCCTGGGGAGTATGCACGCAAGTGTG


AAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTC


GAAGCAACGCGAAGAACCTTACCAGGCCTTGACATGGAAACAAATACCCTAGAGAT


AGGGGGATAATTATGGATCACACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGT


GAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTCGCATGTTACCAGCAT


CAAGTTGGGGACTCATGCGAGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATG


ACGTCAAATCATCATGCCCCTTATGGCCTGGGCTACACACGTACTACAATGGCGAC


CACAAAGAGCAGCGACACAGTGATGTGAAGCGAATCTCATAAAGGTCGTCTCAGTT


CGGATTGAAGTCTGCAACTCGACTTCATGAAGTCGGAATCGCTAGTAATCGCAGAT


CAGCATGCTGCGGTGAATACGTTCTCGGGCCTTGTACACACCGCCCGTCAAACCAT


GGGAGTCAGTAATACCCGAAGCCGGTGGCATAACCGTAAGGAGTGAGCCGTCGAA


GGTAGGACCGA





SEQ ID NO: 16 Clostridium_M clostridioforme Strain 16


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTC


GAACGAAGCAATTAAGATGAAGTTTTCGGATGGAATCTTGATTGACTGAGTGGCGG


ACGGGTGAGTAACGCGTGGATAACCTGCCTCACACTGGGGGATAACAGTTAGAAAT


GACTGCTAATACCGCATAAGCGCACAGTGCCGCATGGCAGTGTGTGAAAAACTCCG


GTGGTGTGAGATGGATCCGCGTCTGATTAGCCAGTTGGCGGGGTAACGGCCCACC


AAAGCGACGATCAGTAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGA


CACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGAA


AGCCTGATGCAGCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAAAGCTCTA


TCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCC


AGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAG


GGAGCGTAGACGGCGAAGCAAGTCTGAAGTGAAAACCCGGGGCTCAACCCTGGGA


CTGCTTTGGAAACTGTTTTGCTAGAGTGTCGGAGAGGTAAGTGGAATTCCTAGTGTA


GCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGG


ACGATAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCT


GGTAGTCCACGCCGTAAACGATGAATGCTAGGTGTTGGGGGGCAAAGCCCTTCGG


TGCCGCCGCAAACGCAGTAAGCATTCCACCTGGGGAGTACGTTCGCAAGAATGAAA


CTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAA


GCAACGCGAAGAACCTTACCAAGTCTTGACATCCCCCTGACGGGCCGGTAACGCG


GCCTTTCCTTCGGGACAGGGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGT


CGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTAGTAGCCAG


CAGGTAGAGCCGGGCACTCTAGGGAGACTGCCAGGGATAACCTGGAGGAAGGTGG


GGATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGG


CGTAAACAAAGGGAAGCGAGACAGTGATGTGGAGCAAATCCCAAAAATAACGTCCC


AGTTCGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGC


GAATCAGAATGTCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACA


CCATGGGAGTCAGCAACGCCCGAAGTCAGTGACCCAAC-CGAAAG-


GAGGGAGCTGCCGAAGGGGGGGCAGGTAACTGGGGTGAAGTCGTAACAAGGTAGC


CGTA





SEQ ID NO: 17 Paraclostridium massiliensis Strain 17


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTC


GAGCGATCTCTTCGGAGAGAGCGGCGGACGGGTGAGTAACGCGTGGGTAACCTGC


CCTGTACACACGGATAACATACCGAAAGGTATACTAATACGGGATAACATACGAAAG


TCGCATGGCTTTTGTATCAAAGCTCCGGCGGTACAGGATGGACCCGCGTCTGATTA


GCTAGTTGGTAAGGTAATGGCTTACCAAGGCAACGATCAGTAGCCGACCTGAGAGG


GTGATCGGCCACACTGGAACTGAGACACGGTCCAGACTCCTACGGGAGGCAGCAG


TGGGGAATATTGCACAATGGGCGAAAGCCTGATGCAGCAACGCCGCGTGAGCGAT


GAAGGCCTTCGGGTCGTAAAGCTCTGTCCTCAAGGAAGATAATGACGGTACTTGAG


GAGGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCTAG


CGTTATCCGGAATTACTGGGCGTAAAGGGTGCGTAGGTGGTTTTTTAAGTCAGAAG


TGAAAGGCTACGGCTCAACCGTAGTAAGCTTTTGAAACTAGAGAACTTGAGTGCAG


GAGAGGAGAGTAGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAAT


ACCAGTAGCGAAGGCGGCTCTCTGGACTGTAACTGACACTGAGGCACGAAAGCGT


GGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAGTACTA


GGTGTCGGGGGTTACCCCCCTCGGTGCCGCAGCTAACGCATTAAGTACTCCGCCT


GGGAAGTACGCTCGCAAGAGTGAAACTCAAAGGAATTGACGGGGACCCGCACAAG


TAGCGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCTAAGCTTGAC


ATCCCACTGACCTCTCCCTAATCGGAGATTTCCCTTCGGGGACAGTGGTGACAGGT


GGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGA


GCGCAACCCTTGCCTTTAGTTGCCAGCATTAAGTTGGGCACTCTAGAGGGACTGCC


GAGGATAACTCGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGCTT


AGGGCTACACACGTGCTACAATGGGTGGTACAGAGGGTTGCCAAGCCGCGAGGTG


GAGCTAATCCCTTAAAGCCATTCTCAGTTCGGATTGTAGGCTGAAACTCGCCTACAT


GAAGCTGGAGTTACTAGTAATCGCAGATCAGAATGCTGCGGTGAATGCGTTCCCGG


GTCTTGTACACACCGCCCGTCACACCATGGAAGTTGGGGGCGCCCGAAGCCGGTT


AGCTAACCTTTTAGGAAGCGGCCGTCGAAGGTGAAACCAATGACTGGGGTGAAGTC


GTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCT





SEQ ID NO: 18 Dorea longicatena B Strain 18


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTC


GAGCGAAGCACTTAAGTCTGA-TTCTTCGGA-


TGAAGACTTTTGTGACTGAGCGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCC


TCATACAGGGGGATAACAGTTAGAAATGACTGCTAATACCGCATAAGACCACGGTA


CCGCATGGTACAGTGGTAAAAACTCCGGTGGTATGAGATGGACCCGCGTCTGATTA


GGTAGTTGGTGGGGTAACGGCCTACCAAGCCGACGATCAGTAGCCGACCTGAGAG


GGTGACCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCA


GTGGGGAATATTGCACAATGGAGGAAACTCTGATGCAGCGACGCCGCGTGAAGGA


TGAAGTATTTCGGTATGTAAACTTCTATCAGCAGGGAAGAAAATGACGGTACCTGAC


TAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAG


CGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGCACGGCAAGCCAGAT


GTGAAAGCCCGGGGCTCAACCCCGGGACTGCATTTGGAACTGCTG-


AGCTAGAGTGTCGGAGAGGCAAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGA


TATTAGGAGGAACACCAGTGGCGAAGGCGGCTTGCTGGACGATGACTGACGTTGA


GGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTA


AACGATGACTGCTAGGTGTCGGGTGGCAAAGCCATTCGGTGCCGCAGCTAACGCA


ATAAGCAGTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACG


GGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACC


TTACCTGATCTTGACATCCCGATGACCG-


CTTCGTAATGGAAGCTTTTCTTCGGAACATCGGTGACAGGTGGTGCATGGTTGTCG


TCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATCT


TCAGTAGCCAGCAGGTTAAGCTGGGCACTCTGGAGAGACTGCCAGGGATAACCTG


GAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCAGGGCTACACAC


GTGCTACAATGGCGTAAACAAAGAGAAGCGA-


ACTCGCGAGGGTAAGCAAATCTCAAAAATAACGTCTCAGTTCGGATTGTAGTCTGCA


ACTCGACTACATGAAGCTGGAATCGCTAGTAATCGCAGATCAGAATGCTGCGGTGA


ATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACGCC


CGAAGTCAGTGACCCAACCGTAAGGAGGGAGCTGCCGAAGGTGGGACCGATAACT


GGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCT


T





SEQ ID NO: 19 Bacteroides thetaiotaomicron Strain 19


ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCA


AGTCGAGGGGCAGCATTTCAGTTTGCTTGCAAACTGGAGATGGCGACCGGCGCAC


GGGTGAGTAACACGTATCCAACCTGCCGATAACTCGGGGATAGCCTTTCGAAAGAA


AGATTAATACCCGATGGCATAAT-


AGAACCGCATGGTTTTTTTATTAAAGAATTTCGGTTATCGATGGGGATGCGTTCCAT


TAGGCAGTTGGTGAGGTAACGGCTCACCAAACCTTCGATGGATAGGGGTTCTGAGA


GGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGC


AGTGAGGAATATTGGTCAATGGACG-


AGAGTCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTT


CTTTTATATGGGAATAAAGTTTTCCACGTGTGGAATTTTGTATGTACCATATGAATAA


GGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTAT


CCGGATTTATTGGGTTTAAAGGGAGCGTAGGTGGACAGTTAAGTCAGTTGTGAAAG


TTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGCTGTCTTGAGTACAGTAGAGG


TGGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGAT


TGCGAAGGCAGCTCACTGGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATC


AAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTG


CGATATACAGTAAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGC


CGGCAAC-


GGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTT


AATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCATTTGAATATATTGG


AAACAGTATAGTCGTAAGACAAATGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGT


GCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTA


ACAGGTCATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTG


GGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAAT


GGGGGGTACAGAAGGCAGCTACCTGGTGACAGGATGCTAATCCCAAAAGCCTCTCT


CAGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCG


CGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTC


AAGCCATGAAAGCCGGGGGTACCTGAAGTACGTAACCGCAAGGAGCGTCCTAGGG


TAAAACTGGTAATTGGGGC





SEQ ID NO: 20 Parabacteroides distasonis Strain 20


CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCTTAACACATGCAA


GTCGAGGGGCAGCACAG-GTAGCAATAC-


CGGGTGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACTTGCCTATCAGAGG


GGGATAACCCGGCGAAAGTCGGACTAATACCGCATGAAGCAGGGATCCCGCATGG


GAATATTTGCTAAAGATTCATCGCTGATAGATAGGCATGCGTTCCATTAGGCAGTTG


GCGGGGTAACAGCCCACCAAACCGACGATGGATAGGGGTTCTGAGAGGAAGGTCC


CCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAAT


ATTGGTCAATGGCCGAGAGGCTGAACCAGCCAAGTCGCGTGAGGGATGAAGGTTC


TATGGATCGTAAACCTCTTTTATAAGGGAATAAAGTGCGGGACGTGTCCCGTTTTGT


ATGTACCTTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGG


AGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCCTTTT


AAGTCAGCGGTGAAAGTCTGTGGCTCAACCATAGAATTGCCGTTGAAACTGGGGGG


CTTGAGTATGTTTGAGGCAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATA


TCACGCAGAACCCCGATTGCGAAGGCAGCCTGCCAAGCCATGACTGACGCTGATG


CACGAAAGCGTGGGGATCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAAC


GATGATCACTAGCTGTTTGCGATACACTGTAAGCGGCACAGCGAAAGCGTTAAGTG


ATCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCC


CGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCG


GGTTTGAACGCATTCGGACCGAGGTGGAAACACCTTTTCTAGCAATAGCCGTTTGC


GAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCAT


AACGAGCGCAACCCTTGCCACTAGTTACTAACAGGTAAAGCTGAGGACTCTGGTGG


GACTGCCAGCGTAAGCTGCGAGGAAGGCGGGGATGACGTCAAATCAGCACGGCCC


TTACATCCGGGGCGACACACGTGTTACAATGGCGTGGACAAAGGGAAGCCACCTG


GCGACAGGGAGCGAATCCCCAAACCACGTCTCAGTTCGGATCGGAGTCTGCAACC


CGACTCCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAAT


ACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCGGGGGTACCT


GAAGTCCGTAACCGCGAGGATCGGCCTAGGGTAAAACTGGTGACTGGGGCTAAGT


CGTAACAAG





SEQ ID NO: 21 Escherichia coli Strain 21


TTGAAGAGTTTGATCATGGCTCAGATTGAACGCTGGCGGCAGGCCTAACACATGCA


AGTCGAACGGTAACAGGAAGCAGCTTGCTGCTTTGCTGACGAGTGGCGGACGGGT


GAGTAATGTCTGGGAAACTGCCTGATGGAGGGGGATAACTACTGGAAACGGTAGCT


AATACCGCATAACGTCGCAAGACCAAAGAGGGGGACCTTCGGGCCTCTTGCCATCG


GATGTGCCCAGATGGGATTAGCTAGTAGGTGGGGTAACGGCTCACCTAGGCGACG


ATCCCTAGCTGGTCTGAGAGGATGACCAGCCACACTGGAACTGAGACACGGTCCAG


ACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGC


AGCCATGCCGCGTGTATGAAGAAGGCCTTCGGGTTGTAAAGTACTTTCAGCGGGGA


GGAAGGGAGTAAAGTTAATACCTTTGCTCATTGACGTTACCCGCAGAAGAAGCACC


GGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGGTGCAAGCGTTAATCGGA


ATTACTGGGCGTAAAGCGCACGCAGGCGGTTTGTTAAGTCAGATGTGAAATCCCCG


GGCTCAACCTGGGAACTGCATCTGATACTGGCAAGCTTGAGTCTCGTAGAGGGGG


GTAGAATTCCAGGTGTAGCGGTGAAATGCGTAGAGATCTGGAGGAATACCGGTGGC


GAAGGCGGCCCCCTGGACGAAGACTGACGCTCAGGTGCGAAAGCGTGGGGAGCAA


ACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGTCGACTTGGAGGTTGT


GCCCTTGAGGCGTGGCTTCCGGAGCTAACGCGTTAAGTCGACCGCCTGGGGAGTA


CGGCCGCAAGGTTAAAACTCAAATGAATTGACGGGGGCCCGCACAAGCGGTGGAG


CATGTGGTTTAATTCGATGCAACGCGAAGAACCTTACCTGGTCTTGACATCCACGGA


AGTTTTCAGAGATGAGAATGTGCCTTCGGGAACCGTGAGACAGGTGCTGCATGGCT


GTCGTCAGCTCGTGTTGTGAAATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTT


ATCCTTTGTTGCCAGCGGTCCGGCCGGGAACTCAAAGGAGACTGCCAGTGATAAAC


TGGAGGAAGGTGGGGATGACGTCAAGTCATCATGGCCCTTACGACCAGGGCTACA


CACGTGCTACAATGGCGCATACAAAGAGAAGCGACCTCGCGAGAGCAAGCGGACC


TCATAAAGTGCGTCGTAGTCCGGATTGGAGTCTGCAACTCGACTCCATGAAGTCGG


AATCGCTAGTAATCGTGGATCAGAATGCCACGGTGAATACGTTCCCGGGCCTTGTA


CACACCGCCCGTCACACCATGGGAGTGGGTTGCAAAAGAAGTAGGTAGCTTAACCT


TCGGGAGGGCGCTTACCACTTTGTGATTCATGACTGGGGTGAAGTCGTAACAAGGT


AACCGTAGGGGAACCTGCGGTTGGATCACCTCCTT





SEQ ID NO: 22 Bifidobacterium longum Strain 22


TGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCGAACGGGATCC


ATCAGGCTTTGCTTGGTGGTGAGAGTGGCGAACGGGTGAGTAATGCGTGACCGAC


CTGCCCCATACACCGGAATAGCTCCTGGAAACGGGTGGTAATGCCGGATGCTCCAG


TTGATCGCATGGTCTTCTGGGAAAGCTTTCGCGGTATGGGATGGGGTCGCGTCCTA


TCAGCTTGACGGCGGGGTAACGGCCCACCGTGGCTTCGACGGGTAGCCGGCCTGA


GAGGGCGACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGGAGGCA


GCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAGCGACGCCGCGTGAG


GGATGGAGGCCTTCGGGTTGTAAACCTCTTTTATCGGGGAGCAAGCGAGAGTGAGT


TTACCCGTTGAATAAGCACCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAG


GGTGCAAGCGTTATCCGGAATTATTGGGCGTAAAGGGCTCGTAGGCGGTTCGTCGC


GTCCGGTGTGAAAGTCCATCGCTTAACGGTGGATCCGCGCCGGGTACGGGGGGGC


TTGAGTGCGGTAGGGGAGACTGGAATTCCCGGTGTAACGGTGGAATGTGTAGATAT


CGGGAAGAACACCAATGGCGAAGGCAGGTCTCTGGGCCGTTACTGACGCTGAGGA


GCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAAC


GGTGGATGCTGGATGTGGGGCCCGTTCCACGGGTTCCGTGTCGGAGCTAACGCGT


TAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGAAATTGACGG


GGGCCCGCACAAGCGGCGGAGCATGCGGATTAATTCGATGCAACGCGAAGAACCT


TACCTGGGCTTGACATGTTCCCGACGGTCGTAGAGATACGGCTTCCCTTCGGGGCG


GGTTCACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAG


TCCCGCAACGAGCGCAACCCTCGCCCCGTGTTGCCAGCGGATTATGCCGGGAACT


CACGGGGGACCGCCGGGGTTAACTCGGAGGAAGGTGGGGATGACGTCAGATCATC


ATGCCCCTTACGTCCAGGGCTTCACGCATGCTACAATGGCCGGTACAACGGGATGC


GACGCGGCGACGCGGAGCGGATCCCTGAAAACCGGTCTCAGTTCGGATCGCAGTC


TGCAACTCGACTGCGTGAAGGCGGAGTCGCTAGTAATCGCGAATCAGCAACGTCGC


GGTGAATGCGTTCCCGGGCCTTGTACACACCGCCCGTCAAGTCATGAAAGTGGGCA


GCACCCGAAGCCGGTGGCCTAACCCCTTGTGGGATGGAGCCGTCTAAGGTGAGGC


TCGTGATTGGGACTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGATC


ACCTCCTT





SEQ ID NO: 23 Absiella innocuum Strain 23


ATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCATGCCTAATACATGCA


AGTCGAACGAAGT-


TTCGAGGAAGCTTGCTTCCAAAGAGACTTAGTGGCGAACGGGTGAGTAACACGTAG


GTAACCTGCCCATGTGTCCGGGATAACTGCTGGAAACGGTAGCTAAAACCGGATAG


GTATACAGAGCGCATGCTCAGTATATTAAAGCGCCCATCAAGGCGTGAACATGGAT


GGACCTGCGGCGCATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGATGATG


CGTAGCCGGCCTGAGAGGGTAAACGGCCACATTGGGACTGAGACACGGCCCAAAC


TCCTACGGGAGGCAGCAGTAGGGAATTTTCGTCAATGGGGGAAACCCTGAACGAG


CAATGCCGCGTGAGTGAAGAAGGTCTTCGGATCGTAAAGCTCTGTTGTAAGTGAAG


AACGGCTCATAGAGGAAATGCTATGGGAGTGACGGTAGCTTACCAGAAAGCCACGG


CTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGAATC


ATTGGGCGTAAAGGGTGCGTAGGTGGCGTACTAAGTCTGTAGTAAAAGGCAATGGC


TCAACCATTGTAAGCTATGGAAACTGGTATGCTGGAGTGCAGAAGAGGGCGATGGA


ATTCCATGTGTAGCGGTAAAATGCGTAGATATATGGAGGAACACCAGTGGCGAAGG


CGGTCGCCTGGTCTGTAACTGACACTGAGGCACGAAAGCGTGGGGAGCAAATAGG


ATTAGATACCCTAGTAGTCCACGCCGTAAACGATGAGAACTAAGTGTTGGAGGAATT


CAGTGCTGCAGTTAACGCAATAAGTTCTCCGCCTGGGGAGTATGCACGCAAGTGTG


AAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTC


GAAGCAACGCGAAGAACCTTACCAGGCCTTGACATGGAAACAAATACCCTAGAGAT


AGGGGGATAATTATGGATCACACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGT


GAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTCGCATGTTACCAGCAT


CAAGTTGGGGACTCATGCGAGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATG


ACGTCAAATCATCATGCCCCTTATGGCCTGGGCTACACACGTACTACAATGGCGGC


CACAAAGAGCAGCGACACAGTGATGTGAAGCGAATCTCATAAAGGTCGTCTCAGTT


CGGATTGAAGTCTGCAACTCGACTTCATGAAGTCGGAATCGCTAGTAATCGCAGAT


CAGCATGCTGCGGTGAATACGTTCTCGGGCCTTGTACACACCGCCCGTCAAACCAT


GGGAGTCAGTAATACCCGAAGCCGGTGGCATAACCGTAAGGAGTGAGCCGTCGAA


GGTAGGACCGA





SEQ ID NO: 24 Fusobacterium_A sp Strain 24


AGAGTTTGATCCTGGCTCAGGATGAACGCTGACAGAATGCTTAACACATGCAAGTC


TA-


CTTGATCCTTCGGGTGATGGTGGGGGACGGGTGAGTAACGCGTAAAGAACTTGCCC


TGCAGTCTGGGACAACATTTGGAAACGAATGCTAATACCGGATATTATGT-


ATTTCTCGCATGAGTTTTACATGAAAGCTATATGCGCTGCAGGAGAGCTTTGCGTCC


TATTAGCTAGTTGGTGAGGTAACGGCTCACCAAGGCCATGATAGGTAGCCGGCCTG


AGAGGGTGAACGGCCACAAGGGGACTGAGACACGGCCCTTACTCCTACGGGAGGC


AGCAGTGGGGAATATTGGACAATGGACCAAAAGTCTGATCCAGCAATTCTGTGTGC


ACGATGAAGTTTTTCGGAATGTAAAGTGCTTTCAGTTGGGACGAAGTAAGTGACGGT


ACCAACAGAAGAAGCGACGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGT


CGCAAGCGTTATCCGGATTTATTGGGCGTAAAGCGCGTC-


TAGGCGGTTTGGTAAGTCTGATGTGAAAATGCGGGGCTCAACTCCGTATTGCGTTG


GAAACTG-


CTAAACTAGAGTACTGGAGAGGTGGGGGGAACTACAAGTGTAGAGGTGAAATTCGT


AGATATTTGTAGGAATGCCGATGGGGAAGCCAGCCCACTGGACAGATACTGACGCT


AAAGCGCGAAAGCGTGGGTAGCAAACAGGATTAGATAC-----


CCTGGTAGTCCACGCCGTAAACGATGATTACTAGGTGTTGGGGGTCGAACCTCAGC


GCCCAAGCTAACGCGATAAGTAATCCGCCTGGGGAGTACGTACGCAAGTATGAAAC


TCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGACG


CAACGCGAGGAACCTTACCAGCGTTTGACATCCTAAGAAATTAGCAGAGATGCTTTT


GTGCCCCTTCGGGGGAACTTAGTGACAGGTGGTGCATGGCTGTCGTCAGCTCGTG


TCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTTTCGTATGTTGCCA


TCATTAAGTTGGGCACTCATGCGATACTGCCTGCGATGAGCAGGAGGAAGGTGGG


GATGACGTCAAGTCATCATGCCCCTTATACGCTGGGCTACACACGTGCTACAATGG


GTAGTACAGAGAGTCGCAAACCTGCGAGGGGGAGCTAATCTCAGAAAACTATTCTC


AGTTCGGATTGTACTCTGCAACTCGAGTACATGAAGTTGGAATCGCTAGTAATCGCA


AATCAGCTATGTTGCGGTGAATACGTTCTCGGGTCTTGTACACACCGCCCGTCACA


CCACGAGAGTTGGTTGCACCTGAAGTAGCAGGCCTAACCGCAAGGAGGGATGCTC


CGAGGGTGTGATTAGCGATTGGGGTGAAGTCGTAACAAGGTATCCGTACGGGAAC


GTGCGGATGGATCACCTCCTT





SEQ ID NO: 25 Parabacteroides merdae Strain 25


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCTTAACACATGCAAGTC


GAGGGGCAGCATGATTTGTAGCAATACAGATTGATGGCGACCGGCGCACGGGTGA


GTAACGCGTATGCAACTTACCTATCAGAGGGGGATAGCCCGGCGAAAGTCGGATTA


ATACCCCATAAAACAGGGGTCCCGCATGGGAATATTTGTTAAAGATTCATCGCTGAT


AGATAGGCATGCGTTCCATTAGGCAGTTGGGGGGTAACGGCCCACCAAACCGAC


GATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGTACTGAGACACGGACC


AAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGCCGAGAGGCTGAA


CCAGCCAAGTCGCGTGAAGGAAGAAGGATCTATGGTTTGTAAACTTCTTTTATAGGG


GAATAAAGTGGAGGACGTGTCCTTTTTTGTATGTACCCTATGAATAAGCATCGGCTA


ACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATGCGAGCGTTATCCGGATTTATT


GGGTTTAAAGGGTGCGTAGGTGGTGATTTAAGTCAGCGGTGAAAGTTTGTGGCTCA


ACCATAAAATTGCCGTTGAAACTGGGTTACTTGAGTGTGTTTGAGGTAGGCGGAAT


GCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACTCCGATTGCGAAGGCA


GCTTACTAAACCATAACTGACACTGAAGCACGAAAGCGTGGGGATCAAACAGGATT


AGATACCCTGGTAGTCCACGCAGTAAACGATGATTACTAGGAGTTTGCGATACAATG


TAAGCTCTACAGCGAAAGCGTTAAGTAATCCACCTGGGGAGTACGCCGGCAACGGT


GAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATT


CGATGATACGCGAGGAACCTTACCCGGGTTTGAACGTAGTCTGACCGGAGTGGAAA


CACTCTTTCTAGCAATAGCAGATTACGAGGTGCTGCATGGTTGTCGTCAGCTCGTG


CCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCACTAGTTACTA


ACAGGTGAAGCTGAGGACTCTGGTGAGACTGCCAGCGTAAGCTGTGAGGAAGGTG


GGGATGACGTCAAATCAGCACGGCCCTTACATCCGGGGCGACACACGTGTTACAAT


GGCATGGACAAAGGGCAGCTACCTGGTGACAGGATGCTAATCTCCAAACCATGTCT


CAGTTCGGATCGGAGTCTGCAACTCGACTCCGTGAAGCTGGATTCGCTAGTAATCG


CGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTC


AAGCCATGGGAGCCGGGGGTACCTGAAGTCCGTAACCGCAAGGATCGGCCTAGGG


TAAAACTGGTGACTGGGGCTAAGTCGTAACAAGGTA





SEQ ID NO: 26 Coprococcus_B comes Strain 26


GAGAGTTTGATCCTGGCTCAGGATGAACGCTGGC-GG-


CGTGCTTAACACATGCAAGTCGAACGAAGCACTTACCTTTGA-TTCTTCGGA-


TGAAGGTTTTTG-


TGACTGAGTGGGGGACGGGTGAGTAACGCGTGGGTAACCTGCCTCATACAGGGGG


ATAACAGTTAGAAATGACTGCTAATACCGCATAAGACCACAGAGCTGCATGGCTCA


GTGGGAAAAACTCCGGTGGTATGAGATGGACCCGCGTCTGATTAGGTAGTTGGTGG


GGTAACGGCCTACCAAGCCAACGATCAGTAGCCGACCTGAGAGGGTGACCGGCCA


CATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATT


GCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAGCGAAGAAGTATTTCG


GTATGTAAAGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCACC


GGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGGTGCAAGCGTTATCCGGAT


TTACTGGGTGTAAAGGGAGCGTAGACGGCTGTGTAAGTCTGAAGTGAAAGCCCGG


GGCTCAACCCCGGGACTGCTTTGGAAACTATGCAGCTAGAGTGTCGGAGAGGTAAG


TGGAATTCCCAGTGTAGCGGTGAAATGCGTAGATATTGGGAGGAACACCAGTGGCG


AAGGCGGCTTACTGGACGATGACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAA


CAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGACTACTAGGTGTCGGGG


AGCAGAGCTCTTCGGTGCCGCAGCAAACGCAATAAGTAGTCCACCTGGGGAGTAC


GTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGC


ATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCTGCTCTTGACATCCCGGTGA


CCGG-


CATGTAATGATGCCTTTTCTTCGGAACACCGGTGACAGGTGGTGCATGGTTGTCGT


CAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCTT


CAGTAGCCAGCAATTCGGATGGGCACTCTGGAGAGACTGCCAGGGATAACCTGGA


GGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGAGCAGGGCTACACACGT


GCTACAATGACGTAAACAAAGGGAAGCGAGCCTGCGAGGGTAAGCAAATCTCAAAA


ATAACGTCTCAGTTCGGATTGTAGTCTGCAACTCGACTACATGAAGCTGGAATCGCT


AGTAATCGCGAATCAGCATGTCGCGGTGAATACGTTCCCGGGTCTTGTACACACCG


CCCGTCACACCATGGGAGTTGGTAACGCCCGAAGTCAGTGACCCAACCGTAAGGA


GGGAGCTGCCGAAGGTGGGACCGATAACTGGGGTGAAGTCGTAACAAGGTAGCCG


TATCGGAAGGTGCGGCTGGATCACCTCC





SEQ ID NO: 27 Agathobacter rectale Strain 27


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTC


GAACGAAGCACTTTATTTGATTTCCTTCGGGACTGATTATTTTGTGACTGAGTGGCG


GACGGGTGAGTAACGCGTGGGTAACCTGCCTTGTACAGGGGGATAACAGTTGGAA


ACGGCTGCTAATACCGCATAAGCGCACGGCATCGCATGATGCAGTGTGAAAAACTC


CGGTGGTATAAGATGGACCCGCGTTGGATTAGCTAGTTGGTGAGGTAACGGCCCAC


CAAGGCGACGATCCATAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAG


ACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGA


AAGCCTGATGCAGCGACGCCGCGTGAGCGAAGAAGTATTTCGGTATGTAAAGCTCT


ATCAGCAGGGAAGATAATGACGGTACCTGACTAAGAAGCACCGGCTAAATACGTGC


CAGCAGCCGCGGTAATACGTATGGTGCAAGCGTTATCCGGATTTACTGGGTGTAAA


GGGAGCGCAGGCGGTGCGGCAAGTCTGATGTGAAAGCCCGGGGCTCAACCCCGG


TACTGCATTGGAAACTGTCGTACTAGAGTGTCGGAGGGGTAAGCGGAATTCCTAGT


GTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACT


GGACGATAACTGACGCTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATAC


CCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTTGGGAAGCATTGCTTCTC


GGTGCCGTCGCAAACGCAGTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGA


AACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCG


AAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCTTCTGACCGGTACTTAACCGT


ACCTTCTCTTCGGAGCAGGAGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTC


GTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCTTTAGTAGCCAGC


GGTTCGGCCGGGCACTCTAGAGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGG


ATGACGTCAAATCATCATGCCCCTTATGACTTGGGCTACACACGTGCTACAATGGC


GTAAACAAAGGGAAGCAAAGCTGTGAAGCCGAGCAAATCTCAAAAATAACGTCTCA


GTTCGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGCA


GATCAGAATGCTGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACAC


CATGGGAGTTGGGAATGCCCGAAGCCAGTGACCTAACCGAAAGGAAGGAGCTGTC


GAAGGCAGGCTCGATAACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGG


TGCGGCTGGATCACCT





SEQ ID NO: 28 Erysipelatoclostridium ramosum Strain 28


GAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAATACATGCAAGT


CGAACGCGAGCACTTGTGCTCGAGTGGCGAACGGGTGAGTAATACATAAGTAACCT


GCCCTAGACAGGGGGATAACTATTGGAAAC-


GATAGCTAAGACCGCATAGGTACGGACACTGCATGGTGACCGTATTAAAAGTGCCT


CAAAGCACTGGTAGAGGATGGACTTATGGCGCATTAGCTGGTTGGCGGGGTAACG


GCCCACCAAGGCGACGATGCGTAGCCGACCTGAGAGGGTGACCGGCCACACTGGG


ACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTAGGGAATTTTCGGCAAT


GGGGGAAACCCTGACCGAGCAACGCCGCGTGAAGGAAGAAGGTTTTCGGATTGTA


AACTTCTGTTATAAAGGAAGAACGGGGGCTACAGGAAATGGTAGCCGAGTGACGGT


ACTTTA--


TTAGAAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAG


CGTTATCCGGAATTATTGGGCGTAAAGAGGGAGCAGGGGGCAGCAAGGGTCTGTG


GTGAAAGCCTGAAGCTTAACTTCAGTAAGCCATAGAAACCAGGCAGCTAGAGTGCA


GGAGAGGATCGTGGAATTCCATGTGTAGCGGTGAAATGCGTAGATATATGGAGGAA


CACCAGTGGCGAAGGCGACGATCTGGCCTGCAACTGACGCTCAGTCCCGAAAGCG


TGGGGAGCAAATAGGATTAGATACCCTAGTAGTCCACGCCGTAAACGATGAGTACT


AAGTGTTGGATGTCAAAGTTCAGTGCTGCAGTTAACGCAATAAGTACTCCGCCTGA


GTAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCG


GTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACAT


ACTCATAAAGGCTCCAGAGATGGAGAGATAGCTATATGAGATACAGGTGGTGCATG


GTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACC


CTTATCGTTAGTTACCATCATTAAGTTGGGGACTCTAGCGAGACTGCCAGTGACAAG


CTGGAGGAAGGCGGGGATGACGTCAAATCATCATG-CCCTTATGACCTGGGCT--


ACACGTGCTACAATGGATGGTGCAGAGAGAGGCGAGCCGCG-


GGCGAAACAAAAGCCCATAAAA-CCATT-


TCAGTTCCGGATTGTAGTCTGCAACTCGACTTTATTACATGAGAGTTGGAATCGCTA


GTAATCGCGAATCAGCATGTCGCGGTTTGAATACGTTCTCGGGCCTT-


ACCGCCCGTCACACCAA-AGGATTGATAACAC--G--GC-GGTGG-


CTAACCGCAAGGAAAG-


GCTGTCTAAGGTGGGATTGATGATTGGGGTAAAGTCGTAACGAAGGTATCCCTACG


GGAACGTGGGGATGGATCACCTCC





SEQ ID NO: 29 Clostridium_M citroniae Strain 29


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTC


GAACGAAGCAATTAGAAAGAAGTTTTCGGATGGATTTCTGATTGACTGAGTGGCGG


ACGGGTGAGTAACGCGTGGATAACCTGCCTCACACTGGGGGATAACAGTTAGAAAT


GGCTGCTAATACCGCATAAGCGCACAGTACCGCATGGTACGGTGTGAAAAACTCCG


GTGGTGTGAGATGGATCCGCGTCTGATTAGTTAGTTGGCGGGGTAACGGCCCACCA


AGACAGCGATCAGTAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGAC


ACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGAAA


GCCTGATGCAGCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAAAGCTCTAT


CAGCAGGGAAGAAACTGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCA


GCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAG


GGAGCGTAGACGGCGAAGCAAGTCTGGAGTGAAAACCCAGGGCTCAACCCTGGGA


CTGCTTTGGAAACTGTTTTGCTAGAGTGTCGGAGAGGTAAGTGGAATTCCTAGTGTA


GCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGG


ACGATAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCT


GGTAGTCCACGCCGTAAACGATGAATGCTAGGTGTTGGGGGGCAAAGCCCTTCGG


TGCCGTCGCAAACGCAATAAGCATTCCACCTGGGGAGTACGTTCGCAAGAATGAAA


CTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAA


GCAACGCGAAGAACCTTACCAAGTCTTGACATCCCCCTGACCGGTCAGTAAAGTGA


CCTTTCCTTCGGGACAGGGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTC


GTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTAGTAGCCAGC


AGGTAAAGCTGGGCACTCTAGGGAGACTGCCAGGGATAACCTGGAGGAAGGTGGG


GATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGGC


GTAAACAAAGGGAAGCGACCCTGCGAAGGCAAGCAAATCCCAAAAATAACGTCCCA


GTTCGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGCG


AATCAGAATGTCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACAC


CATGGGAGTCAGCAACGCCCGAAGTCAGTGACCCAAC-CGAAAG-


GAGGGAGCTGCCGAAGGCGGGGCAGGTAACTGGGGTGAAGTCGTAACAAGGTAGC


CGTA





SEQ ID NO: 30 Bacteroides faecis Strain 30


ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCA


AGTCGAGGGGCATCAGGAAGAAAGCTTGCTTTCTTTGCTGGCGACCGGCGCACGG


GTGAGTAACACGTATCCAACCTGCCCTTTACTCGGGGATAGCCTTTCGAAAGAAAG


ATTAATACCCGATGGCATAATGATTCCGCATGGTTTCATTATTAAAGGATTCCGGTA


AAGGATGGGGATGCGTTCCATTAGGTTGTTGGTGAGGTAACGGCTCACCAAGCCTT


CGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTC


CAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGATAGCCTGAA


CCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATAAAG


GAATAAAGTCGGGTATGCATACCCGTTTGCATGTACTTTATGAATAAGGATCGGCTA


ACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATT


GGGTTTAAAGGGAGCGTAGGTGGA-


TGTTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGG


CTGTCTTGAGTGCAGTTGAGGCAGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTA


GATATCACGAAGAACTCCGATTGCGAAGGCAGCCTGCTAAGCTGCAACTGACATTG


AGGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACGGTA


AACGATGAATACTCGCTGTTTGCGATATACGGCAAGCGGCCAAGCGAAAGCGTTAA


GTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGG


GCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTAC


CCGGGCTTAAATTGCAGTGGAATGATGTGGAAACATGTCAGTGAGCAATCACCGCT


GTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGC


CATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTGATGCTGAGGACTCTGGA


GAGACTGCCATCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGC


CCTTACGTCCGGGGCTACACACGTGTTACAATGGGAGGTACAGAAGGCAGCTACCC


GGCGACGGGATGCCAATCCCCAAAACCTCTCTCAGT





SEQ ID NO: 31 Bacteroides ovatus Strain 31


ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCA


AGTCGAGGGGCAGCATGGTCTTAGCTTGCTAAGGCTGATGGCGACCGGCGCACGG


GTGAGTAACACGTATCCAACCTGCCGTCTACTCTTGGCCAGCCTTCTGAAAGGAAG


ATTAATCCAGGATGGGATCATGAGTTCACATGTCCGCATGATTAAAGGTATTTTCCG


GTAGACGATGGGGATGCGTTCCATTAGATAGTTGGCGGGGTAACGGCCCACCAAAC


CGACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGTACTGAGACACG


GACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGAGAGCC


TGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTAT


AAGGGAATAAAGTCGGGTATGCATACCCGTTTGCATGTACTTTATGAATAAGGATCG


GCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATT


TATTGGGTTTAAAGGGAGCGTAGGTGGACGTTTAAGTCAGTTGTGAAAGTTTGCGG


CTCAACCGTAAAATTGCAGTTGATACTGGATGTCTTGAGTGCAGTTGAGGCAGGCG


GAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAA


GGCAGCCTGCTAAGCTGCAACTGACATTGAGGCTCGAAAGTGTGGGTATCAAACAG


GATTAGATACCCTGGTAGTCCACACGGTAAACGATGAATACTCGCTGTTTGCGATAT


ACGGCAAGCGGCCAAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCA


ACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGT


TTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAGACGAATTACGA


GGAAACTTGTAAGCCGCAAGGCGTCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTC


GTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTA


CTAACAGGTTATGCTGAGGACTCTAGAG-


AGACTGCCATCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCC


CTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAGGGCCGCTACCA


CGCGAGTGGATGCCAATCCCTAAAACCCCTCTCAGTTCGGACTGGAGTCTGCAACC


CGACTCCACGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAAT


ACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCGGGGGTACCT


GAAGTGCGTAACCGCGAGGATCGCCCTAGGGTAAAACTGGTGACTGGGGCTAAGT


CGTAACAAGGTAGCCGTACCGGAAG





SEQ ID NO: 32 Bifidobacterium pseudocatenulatum Strain 32


TTCGATTCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCGAAC


GGGATCCATCAGGCTTTGCTTGGTGGTGAGAGTGGCGAACGGGTGAGTAATGCGT


GACCGACCTGCCCCATACACCGGAATAGCTCCTGGAAACGGGTGGTAATGCCGGA


TGCTCCGACTCCTCGCATGGGGTGTCGGGAAAGATTTCATCGGTATGGGATGGGGT


CGCGTCCTATCAGGTAGTCGGGGGGGTAACGGCCCACCGAGCCTACGACGGGTAG


CCGGCCTGAGAGGGCGACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTA


CGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAGCGACG


CCGCGTGCGGGATGACGGCCTTCGGGTTGTAAACCGCTTTTGATCGGGAGCAAGC


CTTCGGGTGAGTGTACCTTTCGAATAAGCACCGGCTAACTACGTGCCAGCAGCCGC


GGTAATACGTAGGGTGCAAGCGTTATCCGGAATTATTGGGCGTAAAGGGCTCGTAG


GCGGTTCGTCGCGTCCGGTGTGAAAGTCCATCGCTTAACGGTGGATCTGCGCCGG


GTACGGGGGGGCTGGAGTGCGGTAGGGGAGACTGGAATTCCCGGTGTAACGGTGG


AATGTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCTGGGCCGTTAC


TGACGCTGAGGAGCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGTAGTC


CACGCCGTAAACGGTGGATGCTGGATGTGGGGCCCGTTCCACGGGTTCCGTGTCG


GAGCTAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCA


AAGAAATTGACGGGGGCCCGCACAAGCGGCGGAGCATGCGGATTAATTCGATGCA


ACGCGAAGAACCTTACCTGGGCTTGACATGTTCCCGACAGCCGTAGAGATATGGCC


TCCCTTCGGGGGGGGTTCACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGA


GATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTCGCCCTGTGTTGCCAGCACGT


CATGGTGGGAACTCACGGGGGACCGCCGGGGTCAACTCGGAGGAAGGTGGGGAT


GACGTCAGATCATCATGCCCCTTACGTCCAGGGCTTCACGCATGCTACAATGGCCG


GTACAACGGGATGCGACACGGCGACGTGGAGCGGATCCCTGAAAACCGGTCTCAG


TTCGGATTGGAGTCTGCAACCCGACTCCATGAAGGGGGAGTCGCTAGTAATCGCGG


ATCAGCAACGCCGCGGTGAATGCGTTCCCGGGCCTTGTACACACCGCCCGTCAAG


TCATGAAAGTGGGTAGCACCCGAAGCCGGTGGCCTAACCCTTTGTGGATGGAGCC


GTCTAAGGTGAGACTCGTGATTGGGACTAAGTCGTAACAAGGTAGCCGTACCGGAA


GGTGCGGCTGGATCACC





SEQ ID NO: 33 Anaerostipes caccae Strain 33


GCTTAACACATG-


CAAGTCGAACGAAGCATTTAGGATTGAAGTTTTCGGATGGATTTCCTATATGACTGA


GTGGCGGACGGGTGAGTAACGCGTGGGGAACCTGCCCTATACAGGGGGATAACAG


CTGGAAACGGCTGCTAATACCGCATAAGCGCACAGAATCGCATGATTCAGTGTGAA


AAGCCCTGGCAGTATAGGATGGTCCCGCGTCTGATTAGCTGGTTGGTGAGGTAACG


GCTCACCAAGGCGACGATCAGTAGCCGGCTTGAGAGAGTGAACGGCCACATTGGG


ACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAAT


GGGGG-


AAACCCTGATGCAGCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAAAGCTC


TATCAGCAGGGAAGAAAACAGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGT


GCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGAATTACTGGGTGT


AAAGGGTGCGTAGGTGGCATGGTAAGTCAGAAGTGAAAGCCCGGGGCTTAACCCC


GGGACTGCTTTTGAAACTGTCATGCTGGAGTGCAGGAGAGGTAAGCGGAATTCCTA


GTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTA


CTGGACTGTCACTGACACTGATGCACGAAAGCGTGGGGAGCAAACAGGATTAGATA


CCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGGGCCGTAGAGGCTT


CGGTGCCGCAGCAAACGCAGTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATG


AAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTC


GAAGCAACGCGAAGAACCTTACCTGGTCTTGACATCCCAATGACCGAACCTTAACC


GGTTTTTTCTTTCGAGACATTGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGT


CGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATCTTTAGTAGCCAG


CATTTAAGGTGGGCACTCTAGAGAGACTGCCAGGGATAACCTGGAGGAAGGTGGG


GACGACGTCAAATCATCATGCCCCTTATGGCCAGGGCTACACACGTGCTACAATGG


CGTAAACAAAGGGAAGCGAAGTCGTGAGGCGAAGCAAATCCCAGAAATAACGTCTC


AGTTCGGATTGTAGTCTGCAACTCGACTACATGAAGCTGGAATCGCTAGTAATCGTG


AATCAGAATGTCACGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACAC


CATGGGAGTCAGTAACGCCCGAAGTCAGTGACCCAACCGCAAGGAGGGAGCTGCC


GAAGGTGGGACCGATAACTGGGGTGAAGTCGTAACAAGG





SEQ ID NO: 34 Bifidobacterium adolescentis Strain 34


TGTGGAGGGTTCGATTCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGC


AAGTCGAACGGGATC-CCAGGAGCTTGCTCCTGG-


GTGAGAGTGGCGAACGGGTGAGTAATGCGTGACCGACCTGCCCCATACACCGGAA


TAGCTCCTGGAAACGGGTGGTAATGCCGGATGCTCCAGTTGGATGCATGTCCTTCT


GGGAAAGATTC-


ATCGGTATGGGATGGGGTCGCGTCCTATCAGCTTGATGGGGGGGTAACGGCCCAC


CATGGCTTCGACGGGTAGCCGGCCTGAGAGGGCGACCGGCCACATTGGGACTGAG


ATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGC


AAGCCTGATGCAGCGACGCCGCGTGCGGGATGACGGCCTTCGGGTTGTAAACCGC


TTTTGACTGGGAGCAAGCCCTTCGGGGTGAGTGTACCTTTCGAATAAGCACCGGCT


AACTACGTGCCAGCAGCCGCGGTAATACGTAGGGTGCAAGCGTTATCCGGAATTAT


TGGGCGTAAAGGGCTCGTAGGCGGTTCGTCGCGTCCGGTGTGAAAGTCCATCGCT


TAACGGTGGATCCGCGCCGGGTACGGGGGGCTTGAGTGCGGTAGGGGAGACTG


GAATTCCCGGTGTAACGGTGGAATGTGTAGATATCGGGAAGAACACCAATGGCGAA


GGCAGGTCTCTGGGCCGTCACTGACGCTGAGGAGCGAAAGCGTGGGGAGCGAACA


GGATTAGATACCCTGGTAGTCCACGCCGTAAACGGTGGATGCTGGATGTGGGGAC


CATTCCACGGTCTCCGTGTCGGAGCCAACGCGTTAAGCATCCCGCCTGGGGAGTA


CGGCCGCAAGGCTAAAACTCAAAGAAATTGACGGGGGCCCGCACAAGCGGCGGAG


CATGCGGATTAATTCGATGCAACGCGAAGAACCTTACCTGGGCTTGACATGTTCCC


GACAGCCCCAGAGATGGGGCCTCCCTTCGGGGGGGGTTCACAGGTGGTGCATGGT


CGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCT


CGCCCTGTGTTGCCAGCACGTCGTGGTGGGAACTCACGGGGGACCGCCGGGGTCA


ACTCGGAGGAAGGTGGGGATGACGTCAGATCATCATGCCCCTTACGTCCAGGGCTT


CACGCATGCTACAATGGCCGGTACAACGGGATGCGACACT-


GTGAGGTGGAGCGGATCCCTTAAAACCGGTCTCAGTTCGGATTGGAGTCTGCAACC


CGACTCCATGAAGGGGAGTCGCTAGTAATCGCGGATCAGCAACGCCGCGGTGAA


TGCGTTCCCGGGCCTTGTACACACCGCCCGTCAAGTCATGAAAGTGGGTAGCACCC


GAAGCCGGTGGCCCAACCTTTTTGGGGGGAGCCGTCTAAGGTGAGACTCGTGATT


GGGACTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGATCACCTCCTT


T





SEQ ID NO: 35 Agathobaculum sp MUR_P3C8a Strain 35


AGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGA


ACGGGGTTATTTTGGAAAATCCTTCGGGATTGGAATTCTT--


AACCTAGTGGCGGACGGGTGAGTAACGCGTGAGCAATCTGCCTTTAAGAGGGGGA


TAACAGTCGGAAACGGCTGCTAATACCGCATAAAGCATTGAATTCGCATGTTTTCGA


TGCCAAAGGAGCAATCCGCTTTTAGATGAGCTCGCGTCTGATTAGCTAGTTGGCGG


GGTAACGGCCCACCAAGGCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCA


CATTGGGACTGA-GACACGGCCCAGACTCCTA-


CGGGAGGCAGCAGTGGGGAATATTGCGCAATGGGGGGAACCCTGACGCAGCAACG


CCGCGTGATTGAAGAAGGCCTTCGGGTTGTAAAGATCTTTAATCAGGGACGAAAC--


ATGACGGTACCTGAAGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTAAT


ACGTAGGGAGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGCGCAGGGGGG


CCGGCAAGTTGGAAGTGAAATCCGGGGGCTTAACCCCCGAACTGCTTTCAAAACTG


CTGGTCTTGAGTGATGGAGAGGCAGGCGGAATTCCGTGTGTAGCGGTGAAATGCG


TAGATATACGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGACATTAACTGACG


CTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGC


CGTAAACGATGGATACTAGGTGTGGGAGGTATTGACCCCTTCCGTGCCGCAGTTAA


CACAATAAGTATCCCACCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATT


GACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCG-


AAGAACCTTACCAGGCCTTGACATCCCGATGACCGGTCTAGAGATAGACCTTCTCTT


CGGAGCATCGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTT


GGGTTAAGTCCCGCAACGAGCGCAACCCTTAC-


GGTTAGTTGATACGCAAGATCACTCTAGCCGGACTGCCGTTGACAAAACGGAGGAA


GGTGGGGACGACGTCAAATCATCATGCCCCTTATGGCCTGGGCTACACACGTACTA


CAATGGCAGTCATACAGAGGGAAGCAAAATCGCGAGGTGGAGCAAATCCCTAAAAG


CTGTCCCAGTTCAGATTGCAGGCTGCAACCCGCCTGCATGAAGTCGGAATTGCTAG


TAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCC


CGTCACACCATGAGAGCCGTCAATACCCGAAGTCCGTAGCCTAACCGTAAGGAGGG


CGCGGCCGAAGGTAGGGGTGGTAATTAGGGTGAAGTCGT





SEQ ID NO: 36 Phascolarctobacterium faecium MUR_P6E9 Strain 36


ATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAACGGA


GAATTTTATTTCGGTAGAATTCTTAGTGGCGAAGGGGTGAGTAACGCGTAGGCAAC


CTGCCCTTTAGACGGGGACAACATTCCGAAAGGAGTGCTAATACCGGATGTGATCA


TCGTGCCGCATGGCAGGATGAAGAAAGATGGCCTCTACAAGTAAGCTATCGCTAAA


GGATGGGCCTGCGTCTGATTAGCTAGTTGGTAGTGTAACGGACTACCAAGGCGATG


ATCAGTAGCCGGTCTGAGAGGATGAACGGCCACATTGGGACTGAGACACGGCCCA


AACTCCTACGGGAGGCAGCAGTGGGGAATCTTCCGCAATGGACGAAAGTCTGACG


GAGCAACGCCGCGTGAGTGATGAAGGATTTCGGTCTGTAAAGCTCTGTTGTTTATG


ACGAACGTGCAGTGTGTGAACAATGCATTGCAATGACGGTAGTAAACGAGGAAGCC


ACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCGAGCGTTGTCCG


GAATTATTGGGCGTAAAGAGCATGTAGGCGGCTTAATAAGTCGAGCGTGAAAATGC


GGGGCTCAACCCCGTATGGCGCTGGAAACTGTTAGGCTTGAGTGCAGGAGAGGAA


AGGGGAATTCCCAGTGTAGCGGTGAAATGCGTAGATATTGGGAGGAACACCAGTGG


CGAAGGCGCCTTTCTGGACTGTGTCTGACGCTGAGATGCGAAAGCCAGGGTAGCG


AACGGGATTAGATACCCCGGTAGTCCTGGCCGTAAACGATGGGTACTAGGTGTAGG


AGGTATCGACCCCTTCTGTGCCGGAGTTAACGCAATAAGTACCCCGCCTGGGGAGT


ACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGA


GTATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGGCTTGACATTGATTG


AACGCTCTAGAGATAGAGCTTTCCCTTCGGGGACAAGAAAACAGGTGGTGCATGGC


TGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCC


TATCCTATGTTACCAGCAAGTAAAGTTGGGGACTCATGGGAGACTGCCAGGGACAA


CCTGGAGGAAGGCGGGGATGACGTCAAGTCATCATGCCCCTTATGTCTTGGGCTAC


ACACGTACTACAATGGTCGGAAACAGAGGGAAGCGAAGCCGCGAGGCAGAGCAAA


CCCCAGAAACCCGATCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAGT


CGGAATCGCTAGTAATCGCAGGTCAGCATACTGCGGTGAATACGTTCCCGGGCCTT


GTACACACCGCCCGTCACACCACGAAAGTTGGTAACACCCGAAGCCGGTGAGGTAA


CCTATAAGGAGCCAGCCGTCTAAGGTGGGGCCGATGATTGGGGTGAAGTCGTAAC


AAGGTAGC





SEQ ID NO: 37 Akkermansia muciniphila Strain 37


AGAGTTTGATTCTGGCTCAGAACGAACGCTGGGGGCGTGGATAAGACATGCAAGTC


GAACGAGAGAATTGCTAGCTTGCTAATAATTCTCTAGTGGCGCACGGGTGAGTAAC


ACGTGAGTAACCTGCCCCCAAGAGTGGGATAGCCCCGGGAAACTGGGATTAATACC


GCATAAAATCGCAAGATTAAAGCAGCAATGCGCTTGGGGATGGGCTCGCGTCCTAT


TAGTTAGTTGGTGAGGTAACGGCTCACCAAGGCGATGACGGGTAGCCGGTCTGAG


AGGATGTCCGGCCACACTGGAACTGAGACACGGTCCAGACACCTACGGGTGGCAG


CAGTCGAGAATCATTCACAATGGGGGAAACCCTGATGGTGCGACGCCGCGTGGGG


GAATGAAGGTCTTCGGATTGTAAACCCCTGTCATGTGGGAGCAAATTAAAAAGATAG


TACCACAAGAGGAAGAGACGGCTAACTCTGTGCCAGCAGCCGCGGTAATACAGAG


GTCTCAAGCGTTGTTCGGAATCACTGGGCGTAAAGCGTGCGTAGGCGGTTTCGTAA


GTCGTGTGTGAAAGGCGGGGGCTCAACCCCCGGACTGCACATGATACTGCGAGAC


TAGAGTAATGGAGGGGGAACCGGAATTCTCGGTGTAGCAGTGAAATGCGTAGATAT


CGAGAGGAACACTCGTGGCGAAGGGGGGTTCCTGGACATTAACTGACGCTGAGGC


ACGAAGGCCAGGGGAGCGAAAGGGATTAGATACCCCTGTAGTCCTGGCAGTAAAC


GGTGCACGCTTGGTGTGCGGGGAATCGACCCCCTGCGTGCCGGAGCTAACGCGTT


AAGCGTGCCGCCTGGGGAGTACGGTCGCAAGATTAAAACTCAAAGAAATTGACGGG


GACCCGCACAAGCGGTGGAGTATGTGGCTTAATTCGATGCAACGCGAAGAACCTTA


CCTGGGCTTGACATGTAATGAACAACATGTGAAAGCATGCGACTCTTCGGAGGCGT


TACACAGGTGCTGCATGGCCGTCGTCAGCTCGTGTCGTGAGATGTTTGGTTAAGTC


CAGCAACGAGCGCAACCCCTGTTGCCAGTTACCAGCACGTAAAGGTGGGGACTCT


GGCGAGACTGCCCAGATCAACTGGGAGGAAGGTGGGGACGACGTCAGGTCAGTAT


GGCCCTTATGCCCAGGGCTGCACACGTACTACAATGCCCAGTACAGAGGGGGCCG


AAGCCGCGAGGCGGAGGAAATCCTAAAAACTGGGCCCAGTTCGGACTGTAGGCTG


CAACCCGCCTACACGAAGCCGGAATCGCTAGTAATGGCGCATCAGCTACGGCGCC


GTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACATCATGGAAGCCGGTCG


CACCCGAAGTATCTGAAGCCAACCGCAAGGAGGCAGGGTCCTAAGGTGAGACTGG


TAACTGGGATGAAGTCGTAACAAGGTAGCCGTAGGGGAACCTGCGGCTGGATCAC


CTCCTTT





SEQ ID NO: 38 Barnesiella intestinihomins Strain 38


GATGAACGCTAGCGACAGGCCTAACACATGCAAGTCGAGGGGCAGCGAAGAGGTA


GCAATACCTCTGTCGGCGACCGGCGCACGGGTGAGTAACACGTATGCAATCCACCT


GTAACAGGGGGATAACCCGGAGAAATCCGGACTAATACCCCATAATATGGGCGCTC


CGCATGGAGAGTTCATTAAAGAGAGCAATTTTGGTTACAGACGAGCATGCGCTCCA


TTAGCCAGTTGGGGGGGTAACGGCCCACCAAAGCGACGATGGATAGGGGTTCTGA


GAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCA


GCAGTGAGGAATATTGGTCAATGGTCGGCAGACTGAACCAGCCAAGTCGCGTGAG


GGAAGACGGCCCTACGGGTTGTAAACCTCTTTTGTCGGAGAGTAAAGTACGCTACG


TGTAGCGTATTGCAAGTATCCGAAGAAAAAGCATCGGCTAACTCCGTGCCAGCAGC


CGCGGTAATACGGAGGATGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCG


TAGGCGGCACGCCAAGTCAGCGGTGAAATTTCCGGGCTCAACCCGGAGTGTGCCG


TTGAAACTGGCGAGCTAGAGTGCACAAGAGGCAGGCGGAATGCGTGGTGTAGCGG


TGAAATGCATAGATATCACGCAGAACCCCGATTGCGAAGGCAGCCTGCTAGGGTGA


AACAGACGCTGAGGCACGAAAGCGTGGGTATCGAACAGGATTAGATACCCTGGTAG


TCCACGCAGTAAACGATGAATACTAACTGTTTGCGATACAATGTAAGCGGTACAGCG


AAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAA


TTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGA


GGAACCTTACCCGGGCTCAAACGCAGGGGGAATGTCGGTGAAAGCCGGCAGCTAG


TAATAGTCACCTGCGAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTC


GGCTTAAGTGCCATAACGAGCGCAACCCCTATCGACAGTTACTAACGGGTGAAGCC


GAGGACTCTGTCGAGACTGCCGGCGCAAGCCGCGAGGAAGGTGGGGATGACGTCA


AATCAGCACGGCCCTTACGTCCGGGGCGACACACGTGTTACAATGGCAGGTACAGA


AGGCAGCCAGTCAGCAATGACGCGCGAATCCCGAAAACCTGTCTCAGTTCGGATTG


GAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCAT


GGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGAAG


CCGGGAGTACCTGAAGCATGCAACCGCAAGGAGCGTACGAAGGTAATACCGGTAA


CTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGG





SEQ ID NO: 39 Bilophila wadsworthia Strain 39


AGAGTTTGATTCTGGCTCAGATTGAACGCTGGGGGCGTGCTTAACACATGCAAGTC


GAACGTGAAAG-TCCTTCGGGGC-


GAGTAAAGTGGCGCACGGGTGAGTAACGCGTGGATAATCTACCCTTAAGATGGGGA


TAACGGCTGGAAACGGTCGCTAATACCGAATACGCTCCCGATTTTATCGTTGGGGG


GAAAGATGGCCTCTGCTTGCAAGCTATCGCTTAAGGATGAGTCCGCGTCCCATTAG


CTAGTTGGCGGGGTAACGGCCCACCAAGGCAACGATGGGTAGCCGGTCTGAGAGG


ATGACCGGCCACACTGGAACTGGAACACGGTCCAGACTCCTACGGGAGGCAGCAG


TGGGGAATATTGCGCAATGGGCGAAAGCCTGACGCAGCGACGCCGCGTGAGGGAT


GAAGGTTCTCGGATCGTAAACCTCTGTCAGGGGGGAAGAAACCCCCTCGTGTGAAT


AATGCGAG-


GGCTTGACGGTACCCCCAAAGGAAGCACCGGCTAACTCCGTGCCAGCAGCCGCGG


TAATACGGAGGGTGCAAGCGTTAATCGGAATCACTGGGCGTAAAGCGCACGTAGGC


GGCTTG-


GTAAGTCAGGGGTGAAATCCCACAGCCCAACTGTGGAACTGCCTTTGATACTGC-


CAGGCTTGAGTACCGGAGAGGGTGGCGGAATTCCAGGTGTAGGAGTGAAATCCGT


AGATATCTGGAGGAACACCGGTGGCGAAGGCGGCCACCTGGAC-


GGTAACTGACGCTGAGGTGCGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTG


GTAGTCCACGCTGTAAACGATGGGTGCTGGGTG-CTGGGATGTATGTC-


TCGGTGCCGTAGCTAACGCGATAAGCACCCCGCCTGGGGAGTACGGTCGCAAGGC


TGAAACTCAAAGAAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAAT


TCGATGCAACGCGAAGAACCTTACCCAGGCTTGACATCTAGGGAACCCTTCGGAAA


TGAAGGGGTGCCCTTCGGGGAGCCCTAAGACAGGTGCTGCATGGCTGTCGTCAGC


TCGTGCCGTGAGGTGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATCTTCAGT


TGCCAGCAGGTAAGGCTGGGCACTCTGGAGAGACCGCCCCGGTCAACGGGGAGGA


AGGTGGGGACGACGTCAAGTCATCATGGCCCTTACGCCTGGGGCTACACACGTACT


ACAATGGCGCGCACAAAGGGTAGCGAGACCGCGAGGTGGAGCCAATCCCAAAAAA


CGCGTCCCAGTCCGGATTGGAGTCTGCAACTCGACTCCATGAAGTCGGAATCGCTA


GTAATTCGAGATCAGCATGCTCGGGTGAATGCGTTCCCGGGCCTTGTACACACCGC


CCGTCACACCACGAAAGTCGGTTTTACCCGAAGCCGGTGAGCTAACTCGCAAGAGA


AGCAGCCGTCTACGGTAGGGCCGATGATTGGGGTGAAGTCGTAACAAGGTAGCCG


TAGGGGAACCTGCGGCTGGATCACCTCCTT





SEQ ID NO: 40 Blautia faecis Strain 40


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTC


GAACGGGAAATACTTTATTGAAACTTCGGTCGATTTAATTTATTTCTAGTGGCGGAC


GGGTGAGTAACGCGTGGGTAACCTGCCTTATACCGGGGGATAACAGCCAGAAATG


GCTGCTAATACCGCATAAGCGCACAGAACCGCATGGTTCGGTGTGAAAAACTCCGG


TGGTATAAGATGGACCCGCGTTGGATTAGCTAGTTGGCAGGGCAGCGGCCTACCAA


GGCGACGATCCATAGCCGGCCTGAGAGGGTGAACGGCCACATTGGGACTGAGACA


CGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAAC


CCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGTAAACTTCTATC


AGCAGGGAAGATAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAG


CAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGG


GAGCGTAGACGGCGCAGCAAGTCTGATGTGAAAGGCAGGGGCTTAACCCCTGGAC


TGCATTGGAAACTGCTGTGCTTGAGTGCCGGAGGGGTAAGCGGAATTCCTAGTGTA


GCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGG


ACGGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCT


GGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCAGGGAGCACAGCTCTTTGGT


GCCGCCGCAAACGCATTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAAC


TCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAG


CAACGCGAAGAACCTTACCAAATCTTGACATCCCTCTGACCGGGACTTAACCGTCC


CTTTCCTTCGGGACAGGGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGT


GAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATCCTTAGTAGCCAGCAC


G-


ATGGTGGGCACTCTGAGGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGGATGA


CGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGGCGTAAA


CAAAGGGAAGCGAACCTGTGAGGGGGGCAAATCTCAAAAATAACGTCCCAGTTCG


GACTGCAGTCTGCAACTCGACTGCACGAAGCTGGAATCGCTAGTAATCGCGGATCA


GAATGCCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGG


GAGTCAGTAACGCCCGAAGTCAGTGACCTAACCGCAAGGGAGGAGCTGCCGAAGG


CGGGACCGATGACTGGGGTGAAGTCGTAACAAGGTA





SEQ ID NO: 41 Blautia wexlerae Strain 41


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGGGGCGTGCTTAACACATGCAAGTC


GAACGGGAATTACTTTATTGAAGCTTCGGCAGATTTAGCTGGTTTCTAGTGGCGGAC


GGGTGAGTAACGCGTGGGTAACCTGCCTTGTACAGGGGGATAACAGTCAGAAATGA


CTGCTAATACCGCATAAGCGCACAGGACCGCATGGTCCGGTGTGAAAAACTCCGGT


GGTATAAGATGGACCCGCGTTGGATTAGCTTGTTGGTGGGGTAACGGCCCACCAAG


GCGACGATCCATAGCCGGCCTGAGAGGGTGAACGGCCACATTGGGACTGAGACAC


GGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACC


CTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGTAAACTTCTATCA


GCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAG


CAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGG


GAGCGTAGACGGATGGA-


CAAGTCTGATGTGAAAGGCTGGGGCTCAACCCCGGGACTGCATTGGAAACTGCCC


GTCTTGAGTGCCGGAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGA


TATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACGGTAACTGACGTTGAG


GCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCGGTAAA


CGATGAATGCTAGGTGTCGGGTGACAAAGTCATTCGGTGCCGCCGCAAACGCATTA


AGCATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGG


ACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTAC


CAAGTCTTGACATCCCTCTGACCGGAACTTAACCGTTCCTTCCCTTCGGGGCAGAG


GAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTC


CCGCAACGAGCGCAACCCCTATCCCCAGTAGCCAGCATTTAAGGTGGGCACTCTGG


GGAGACTGCCAGGGATAACCTGGAGGAAGGGGGGGATGACGTCAAATCATCATGC


CCCTTATGATTTGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGAAC


CCGCGAGGGTGGGCAAATCCCAAAAATAACGTCCCAGTTCGGACTGTAGTCTGCAA


CCCGACTACACGAAGCTGGAATCGCTAGTAATCGCGGATCAGAATGCCGCGGTGAA


TACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACGCCC


GAAGTCAGTGACCTAACCGTAAGGAGGGAGCTGCCGAAGGCGGGACCGATGACTG


GGGTGAAGTCGTAACAAGGTA





SEQ ID NO: 42 Blautia luti Strain 42


CTGGCTCAGGATGAACGCTGGGGGCGTGCTTAACACATGCAAGTCGAACGGGAAAT


ATTTCATTGAGACTTCGGTGGATTTGATCTATTTCTAGTGGGGGACGGGTGAGTAAC


GCGTGGGTAACCTGCCTTATACAGGGGGATAACAGTCAGAAATGGCTGCTAATACC


GCATAAGCGCACAGAGCTGCATGGCTCAGTGTGAAAAACTCCGGTGGTATAAGATG


GACCCGCGTTGGATTAGCTGGTTGGTGGGGTAACGGCCCACCAAGGCGACGATCC


ATAGCCGGCCTGAGAGGGTGAACGGCCACATTGGGACTGAGACACGGCCCAGACT


CCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGC


GACGCCGCGTGAAGGAAGAAGTATCTCGGTATGTAAACTTCTATCAGCAGGGAAGA


TAGTGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGT


AATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACG


GTGTGGCAAGTCTGATGTGAAAGGCATGGGCTCAACCTGTGGACTGCATTGGAAAC


TGTCATACTTGAGTGCCGGAGGGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGC


GTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACGGTAACTGAC


GTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACG


CCGTAAACGATGAATACTAGGTGTCGGGGAGTATGGCTCTTCGGTGCCGTCGCAAA


CGCAGTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATT


GACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAG


AACCTTACCAAGTCTTGACATCCGCCTGACCGGTCCTTAACCGGACCTTTCCTTCGG


GACAGGAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGG


GTTAAGTCCCGCAACGAGCGCAACCCCTATCCTCAGTAGCCAGCAT-


TTAAGGTGGGCACTCTGGGGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGGAT


GACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGGCGTA


AACAAAGGGAAGCGAGATCGTGAGATGGAGCAAATCCCAAAAATAACGTCCCAGTT


CGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGCGGAT


CAGAATGCCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCAT


GGGAGTCAGTAACGCCCGAAGTCAGTGACCTAACTGCAAAGAAGGAGCTGCCGAA


GGCGGGACCGATGACTGGGGTGAAGTCGTAACAAGGTA





SEQ ID NO: 43 Butyricimonas synergistica Strain 43


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCTTAACACATGCAAGTC


GAGGGGCAGCACGGTGTAGCAATACACTGGTGGCGACCGGCGCACGGGTGAGTAA


CACGTGTGCAACCAACCCCGTACCGGGAGATAACCCGCGGAAACGTGGACTAACAT


CCCATAAGACTCTAGAGCCGCATGGCTCTGGATTTAAAATTCCGGTGGTACGGGAC


GGGCACGCGCGACATTAGGTAGTTGGCGGGGTAACGGCCCACCAAGCCGACGATG


TCTAGGGGTTCTGAGAGGAAGGTCCCCCACACTGGAACTGAGACACGGTCCAGACT


CCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGCGAGCCTGAACCAGC


CAAGTCGCGTGAGGGAAGAATGGTCTATGGCCTGTAAACCTCTTTTGTCAAGGAAG


AATAAAAGGT-ACGTGTACCTTC-


TTGCCAGTACTTGACGAATAAGCATCGGCTAACTCCGTGCCAGCAGCCGCGGTAAT


ACGGGGGATGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGCGCGTAGGGGGG


ACGCCAAGTCAGCGGTAAAAGACTGCAGCTAAACTGTAGCACGCCGTTGAAACTGG


CGACCTGGAGACGAGACGAGGGAGGCGGAACAAGTGAAGTAGCGGTGAAATGCTT


AGATATCACTTGGAACCCCGATAGCGAAGGCAGCTTCCCAGGCTCGATCTGACGCT


GATGCGCGAGAGCGTGGGTAGCGAACAGGATTAGATACCCTGGTAGTCCACGCCG


TAAACGATGCTCACTGGATCTTGGCGATACACTGCCAGGGTTCAAGCGAAAGTATT


AAGTGAGCCACCTGGGGAGTACGTCGGCAACGATGAAACTCAAAGGAATTGACGG


GGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTT


ACCCGGGTTTAAATGTATTTTGCATTTCTTGGAAACAGGAATTCCCTTCGGGGCTAG


ATACAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGGTTAAGTC


CCATAACGAGCGCAACCCCTATCGCCAGTTGCCATCGGTTGAAGCCGGGCACTCTG


TCGAGACTGCCACCGTAAGGTGCGAGGAAGGGGGGGATGACGTCAAATCAGCACG


GCCCTTACACCCGGGGCGACACACGTGTTACAATGGCCGGTACAGAGGGCAGCCA


CGGGGTGACCCGGAGCGAATCTCTAAAGCCGGTCGTAGTTCGGACTGGAGTCTGC


AACCCGACTCCACGAAGTTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGT


GAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGAAGCCGGGAGT


ACCTGAAGATCGTGACCGCGAGGAACGGGCTAGGGTAATACCGGTAACTGGGGCT


AAGTCGTAACAAGGTA





SEQ ID NO: 44 Clostridium bolteae Strain 44


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTC


GAACGAAGCAATT-AAAGGAAGTTTTCGGATGGA-


ATTTGATTGACTGAGTGGCGGACGGGTGAGTAACGCGTGGATAACCTGCCTCACAC


TGGGGGATAACAGTTAGAAATGACTGCTAATACCGCATAAGCGCACAGTACCGCAT


GGTACGGTGTGAAAAACTCCGGTGGTGTGAGATGGATCCGCGTCTGATTAGCCAGT


TGGCGGGGTAACGGCCCACCAAAGCGACGATCAGTAGCCGACCTGAGAGGGTGAC


CGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGG


AATATTGCACAATGGGCGAAAGCCTGATGCAGCGACGCCGCGTGAGTGAAGAAGTA


TTTCGGTATGTAAAGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAA


GCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTAT


CCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGCGAAGCAAGTCTGAAGTGAAAA


CCCAGGGCTCAACCCTGGGACTGCTTTGGAAACTGTTTTGCTAGAGTGTCGGAGAG


GTAAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAG


TGGCGAAGGCGGCTTACTGGACGATAACTGACGTTGAGGCTCGAAAGCGTGGGGA


GCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATGCTAGGTGT


TGGGGGGCAAAGCCCTTCGGTGCCGTCGCAAACGCAGTAAGCATTCCACCTGGGG


AGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTG


GAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCTC


TTGGCCGGCGTGTAACGGCGCCTTCCCTTCGGGGCAAGAGAGACAGGTGGTGCAT


GGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAAC


CCTTATCCTTAGTAGCCAGCAGGTAGAGCTGGGCACTCTAGGGAGACTGCCAGGGA


TAACCTGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGATTTGGGC


TACACACGTGCTACAATGGCGTAAACAAAGGGAAGCAAGACAGTGATGTGGAGCAA


ATCCCAAAAATAACGTCCCAGTTCGGACTGTAGTCTGCAACCCGACTACACGAAGC


TGGAATCGCTAGTAATCGCGAATCAGAATGTCGCGGTGAATACGTTCCCGGGTCTT


GTACACACCGCCCGTCACACCATGGGAGTCAGCAACGCCCGAAGTCAGTGACCCA


ACTCGCAAGAGAGGGAGCTGCCGAAGGCGGGGCAGGTAACTGGGGTGAAGTCGTA


ACAAGGTAGCCGTA





SEQ ID NO: 45 Parasutterella excrementihominis Strain 45


ATTGAACGCTGGCGGAACGCTTTACACATGCAAGTCGAACGGTAACGTGGGGAGGA


GCTTGCTCCACCCCGACGACGAGTGGCGAACGGGTGAGTAATACATCGGAACGTG


TCCGCTTGTGGGGGACAACCAGCCGAAAGGTTGGCTAATACCGCATGAGTTCTACG


GAAGAAAGAGGGGGACCCGCAAGGGCCTCTCGCGAGCGGAGCGGCCGATGACTG


ATTAGCCGGTTGGTGAGGTAACGGCTCACCAAAGCAACGATCAGTAGCTGGTCTGA


GAGGACGACCAGCCACACTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCA


GCAGTGGGGAATTTTGGACAATGGGCGCAAGCCTGATCCAGCTATTCCGCGTGTGG


GATGAAGGCCCTCGGGTTGTAAACCACTTTTGTAGAGAACGAAAAGACACCATCGA


ATAAATGGTGTTGCTGACGGTACTCTAAGAATAAGCACCGGCTAACTACGTGCCAG


CAGCCGCGGTAATACGTAGGGTGCGAGCGTTAATCGGAATTACTGGGCGTAAAGG


GTGCGCAGGCGGTTGAGTAAGACAGATGTGAAATCCCCGAGCTTAACTCGGGAATG


GCATATGTGACTGCTCGACTAGAGTGTGTCAGAGGGAGGTGGAATTCCACGTGTAG


CAGTGAAATGCGTAGATATGTGGAAGAACACCGATGGCGAAGGCAGCCTCCTGGG


ACATAACTGACGCTCAGGCACGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTG


GTAGTCCACGCCCTAAACGATGTTAACTAGTTGTTGGGATGTAACAATCTCAGTAAC


GCAGCCAACGCGAGAAGTTAACCGCCTGGGAAGTACGGTCGCAAGACTAAAACTCA


AAGGAATTGACGGGGACCCGCACAAGCGGTGGATGATGTGGATTAATTCGATGCAA


CGCGAAAAACCTTACCTACCCTTGACATGTCAGGAAGCTCTTGTAATGAGAGCGTG


CCCGCAAGGGAGCCTGAACACAGGTGCTGCATGGCTGTCGTCAGCTCGTGTCGTG


AGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTCACTAGTTGCTACGAAA


GGGCACTCTAGTGAGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATGACGTCA


AGTCCTCATGGCCCTTATGGGTAGGGCTTCACACGTCATACAATGGTCGGAACAGA


GGGCAGCGAAGCCGTGAGGCGGAGCCAATCCCAGAAAACCGATCGTAGTCCGGAT


TGCAGTCTGCAACTCGACTGCATGAAGTCGGAATCGCTAGTAATCGCGGATCAGCA


TGCCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCAAACAATGGGAG


TGGTGTTTACCAGAAGTCGTTAGCCTAACCGCAAGGAGGGCGGCGACCACGGTGA


GCACCGTGACTAATGTTAAGTCGTAACAAGGTAGCCGTACCGGAAGG





SEQ ID NO: 46 Prevotella copri Strain 46


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTC


GAGGGGAAACGATATTGGAAGCTTGCTTCCGATAGGCGTCGACCGGCGCACGGGT


GAGTAACGCGTATCCAACCTGCCCACCACTTGGGGATAACCTTGCGAAAGTAAGAC


TAATACCCAATGATATCTCTAGAAGACATCTGAAAGAGATTAAAGATTTATCGGTGAT


GGATGGGGATGCGTCTGATTAGCTTGTTGGCGGGGTAACGGCCCACCAAGGCGAC


GATCAGTAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCA


AACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGAGAGCCTGAAC


CAGCCAAGTAGCGTGCAGGATGACGGCCCTATGGGTTGTAAACTGCTTTTATAAGG


GAATAAAGTGAGAGTCGTGACTCTTTTTGCATGTACCTTATGAATAAGGACCGGCTA


ATTCCGTGCCAGCAGCCGCGGTAATACGGAAGGTCCGGGCGTTATCCGGATTTATT


GGGTTTAAAGGGAGCGTAGGCCGGAGATTAAGCGTGTTGTGAAATGTAGACGCTCA


ACGTCTGCACTGCAGCGCGAACTGGTTTCCTTGAGTACGCACAAAGTGGGCGGAAT


TCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCA


GCTCACTGGAGCGCAACTGACGCTGAAGCTCGAAAGTGCGGGTATCGAACAGGATT


AGATACCCTGGTAGTCCGCACGGTAAACGATGGATGCCCGCTGTTGGTCTGAATAG


GTCAGCGGCCAAGCGAAAGCATTAAGCATCCCACCTGGGGAGTACGCCGGCAACG


GTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAA


TTCGATGATACGCGAGGAACCTTACCCGGGCTTGAATTGCAGAGGAAGGATTTGGA


GACAATGACGCCCTTCGGGGCCTCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCG


TGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCCTCTCCTTAGTTGC


CATCAGGTTAAGCTGGGCACTCTGGGGGCACTGCCACCGTAAGGTGTGAGGAAGG


TGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACA


ATGGCAGGTACAGAGAGATGGTCCCTTGCAAAACGGATCAAATCCTTAAAGCCTGT


CTCAGTTCGGACTGGGGTCTGCAACCCGACCCCACGAAGCTGGATTCGCTAGTAAT


CGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCG


TCAAGCCATGAAAGCCGGGGGCGCCTAAAGTCCGTGACCGTAAGGAGCGGCCTAG


GGCGAAACTGGTAATTGGGGCTAAGTCGTAACAAGGTA





SEQ ID NO: 47 Ruminococcus faecis Strain 47


TTTGATCCTGGCTCAGGATGAACGCTGGGGGCGTGCTTAACACATGCAAGTCGAAC


GAAGCACCTTGATTTGA-TTCTTCGG-


ATGAAGATCCTGGTGACTGAGTGGCGGACGGGTGAGTAACGCGTGGGTAACCTGC


CTCATACAGGGGGATAACAGTTAGAAATGACTGCTAATACCGCATAAGACCACAGC


ACCGCATGGTGCAGGGGTAAAAACTCCGGTGGTATGAGATGGACCCGCGTCTGATT


AGGTAGTTGGTGGGGTAACGGCCTACCAAGCCGACGATCAGTAGCCGACCTGAGA


GGGTGACCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGC


AGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAGCG


ATGAAGTATTTCGGTATGTAAAGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGA


CTAAGAAGCACCGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGGTGCAAG


CGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGAGTGGCAAGTCTGATG


TGAAAACCCGGGGCTCAACCCCGGGACTGCATTGGAAACT--


GTCAATCTAGAGTACCGGAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCG


TAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACGGTAACTGACGT


TGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCC


GTAAACGATGACTACTAGGTGTCGGGCAGCAAAGCTGTTCGGTGCCGCAGCAAACG


CAATAAGTAGTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGA


CGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAA


CCTTACCTGCTCTTGACATCTCCCTGACCGGCAAGTAATGTTGCCTTTCCTTCGGGA


CAG-


GGATGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAG


TCCCGCAACGAGCGCAACCCCTATCTTTAGTAGCCAGCGGTCAGGCCGGGCACTCT


AGAGAGACTGCCAGGGATAACCTGGAGGAAGGTGGGGATGACGTCAAATCATCAT


GCCCCTTATGAGCAGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAGGCA


GAACCGCGAGGTCGAGCAAATCCCAAAAATAACGTCTCAGTTCGGATTGTAGTCTG


CAACTCGACTACATGAAGCTGGAATCGCTAGTAATCGCGAATCAGAATGTCGCGGT


GAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACG


CCCGAAGTCAGTGACCCAACCGTAAGGAGGGAGCTGCCGAAGGTGGGACCGATAA


CTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTC


CTTT





SEQ ID NO: 48 Bacteroides caccae


TGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCATCAG


TTTGGTTTGCTTGCAAACCAAAGCTGGCGACCGGCGCACGGGTGAGTAACACGTAT


CCAACCTGCCTCATACTCGGGGATAGCCTTTCGAAAGAAAGATTAATATCCGATAGC


ATATATTTCCCGCATGGGTTTTATATTAAAGAAATTCGGTATGAGATGGGGATGCGT


TCCATTAGTTTGTTGGGGGGGTAACGGCCCACCAAGACTACGATGGATAGGGGTTC


TGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAG


GCAGCAGTGAGGAATATTGGTCAATGGACGCGAGTCTGAACCAGCCAAGTAGCGTG


AAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGTTGTCCAC


GTGTGGATTTTTGTATGTACCATATGAATAAGGATCGGCTAACTCCGTGCCAGCAGC


CGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCG


TAGGCGGATTGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTT


GATACTGGCAGTCTTGAGTGCAGTAGAGGTGGGCGGAATTCGTGGTGTAGCGGTG


AAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCCACTGGAGTGTAAC


TGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCC


ACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAA


AGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATT


GACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGG


AACCTTACCCGGGCTTAAATTGCAAATGAATTATGGGGAAACCCATAGGCCGCAAG


GCATTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTT


AAGTGCCATAACGAGCGCAACCCTTATCTTCAGTTACTAACAGGTCATGCTGAGGA


CTCTGGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCA


GCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGC


CGCTACCTGGTGACAGGATGCCAATCCCAAAAACCTCTCTCAGTTCGGATCGAAGT


CTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCG


CGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGG


GGGTACCTGAAGTACGTAACCGCAAGGAGCGTCCTAGGGTAAAACTGGTAATTGGG


GCTAAGTCGTAACAAGGTA





SEQ ID NO: 49 Bacteroides cellulosilyticus/ Bacteroides intestinalis


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTC


GAGGGGCAGCATGACCTAGCAATAGGTTGATGGCGACCGGCGCACGGGTGAGTAA


CACGTATCCAACCTACCGGTTATTCCGGGATAGCCTTTCGAAAGAAAGATTAATACC


GGATAGTATAACGAGAAGGCATCTTTTTGTTATTAAAGAATTTCGATAACCGATGGG


GATGCGTTCCATTAGTTTGTTGGCGGGGTAACGGCCCACCAAGACATCGATGGATA


GGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTA


CGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAG


TAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGT


GAGCCACGTGTGGCTTTTTGTATGTACCATACGAATAAGGATCGGCTAACTCCGTG


CCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAA


AGGGAGCGTAGGCGGACTATTAAGTCAGCTGTGAAAGTTTGCGGCTCAACCGTAAA


ATTGCAGTTGATACTGGTCGTCTTGAGTGCAGTAGAGGTAGGCGGAATTCGTGGTG


TAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTTACTG


GACTGTAACTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCC


TGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACGGCAAGCGG


CCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTC


AAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGAT


ACGCGAGGAACCTTACCCGGGCTTAAATTGCAAATGAATATAGTGGAAACATTATAG


CCGCAAGGCATTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTG


TCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCATGC


TGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTC


AAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAG


AAGGCAGCTACACAGCGATGTGATGCTAATCCCAAAAGCCTCTCTCAGTTCGGATT


GGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCA


CGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAA


GCCGGGGGTACCTGAAGTCCGTAACCGTAAGGAGCGGCCTAGGGTAAAACTGGTA


ATTGGGGCTAAGTCGTA





SEQ ID NO: 50 Bacteroides faecis


CTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATTTC


AGTTTGCTTGCAAACTGGAGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCA


ACCTGCCGATAACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGCAT


AATAGAACCGCATGGTTTTTTTATTAAAGAATTTCGGTTATCGATGGGGATGCGTTC


CATTAGGCAGTTGGTGAGGTAACGGCTCACCAAACCTTCGATGGATAGGGGTTCTG


AGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGC


AGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAA


GGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGTTTTCCACGT


GTGGAATTTTGTATGTACCATATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCC


GCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGT


AGGTGGACAGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTT


GATACTGGCTGTCTTGAGTACAGTAGAGGTGGGGGGAATTCGTGGTGTAGCGGTGA


AATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGACTGCAAC


TGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCC


ACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAA


AGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATT


GACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGG


AACCTTACCCGGGCTTAAATTGCATTTGAATATATTGGAAACAGTATAGTCGTAAGA


CAAATGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTA


AGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCATGCTGAGGACT


CTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCA


CGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGC


TACCTGGTGACAGGATGCTAATCCCAAAAGCCTCTCTCAGTTCGGATCGAAGTCTG


CAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGG


TGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGG


TACCTGAAGTACGTAACCGCAAGGAGCGTCCTAGGGTAAAACTGGTAATTGGGGCT


AAGTCGTAACAAGGTA





SEQ ID NO: 51 Bacteroides ovatus


CGATATCCGGATTTATTGGAGTTT-


AAGGGAGCGTAGGTGGATTGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAA


AATTGCAGTTGAAACTGGCAGTCTTGAGTACAGTAGAGGTGGGCGGAATTCGTGGT


GTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACT


AGACTGTCACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACC


CTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCG


GCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACT


CAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGA


TACGCGAGGAACCTTACCCGGGCTTAAATTGCAACAGAATATATTGGAAACAGTATA


GCCGTAAGGCTGTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGT


GTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTKATG


CTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGT


CAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACA


GAAGGCSGCTACCTGGTGACAGGATGCTAATCCCAAAAACCTCTCTCAGTTCGGAT


CGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCC


ATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAA


GCCGGGGGTACCTGAAGTACGTAACCGCAAGGAGCGTCCTAGGGGTAAAACTGGT


AATTGGGGC





SEQ ID NO: 52 Bacteroides thetaiotaomicron


TTTAAGGGAGCGTAGGTGGACAGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCG


TAAAATTGCAGTTGATACTGGCTGTCTTGAGTACAGTAGAGGTGGGCGGAATTCGT


GGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTC


ACTGGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGAT


ACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAG


CGGCCWAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAA


ACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGA


TGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAWWTGAATAWWYTGGAAACA


GKWTAGYCGYAAGRCAWWTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCG


TGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAG


GTCATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGA


TGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGG


GGTACAGAAGGCAGCTACCTGGTGACAGGATGCTAATCCCAAAAGCCTCTCTCAGT


TCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCA


TCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGC


CATGAAAGCCGGGGGTACCTGAAGTACGTAACCGCA





SEQ ID NO: 53 Bacteroides uniformis


CTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCA


TGAACTTAGCTTGCTAAGTTTGATGGCGACCGGCGCACGGGTGAGTAACACGTATC


CAACCTGCCGATGACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGC


ATAGTTCTTCCGCATGGTAGAACTATTAAAGAATTTCGGTCATCGATGGGGATGCGT


TCCATTAGGTTGTTGGCGGGGTAACGGCCCACCAAGCCTTCGATGGATAGGGGTTC


TGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAG


GCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTG


AAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATACGGGAATAAAGTGAGGCAC


GTGTGCCTTTTTGTATGTACCGTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGC


CGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCG


TAGGCGGACGCTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGT


TGATACTGGGTGTCTTGAGTACAGTAGAGGCAGGCGGAATTCGTGGTGTAGCGGTG


AAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTTGCTGGACTGTAA


CTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTC


CACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGA


AAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAAT


TGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAG


GAACCTTACCCGGGCTTGAATTGCAACTGAATGATGTGGAGACATGTCAGCCGCAA


GGCAGTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGC


TTAAGTGCCATAACGAGCGCAACCCTTATCGATAGTTACCATCAGGTTATGCTGGG


GACTCTGTCGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATC


AGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGG


CAGCTACACGGCGACGTGATGCTAATCCCTAAAGCCTCTCTCAGTTCGGATTGGAG


TCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGC


GCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCG


GGGGTACCTGAAGTGCGTAACCGCGAGGAGCGCCCTAGGGTAAAACTGGTGATTG


GGGCTAAGTCGTAACAAGGTA





SEQ ID NO: 54 Bacteroides vulgatus


ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCA


AGTCGAGGGGCAGCATGGTCTTAGCTTGCTAAGGCCGATGGCGACCGGCGCACGG


GTGAGTAACACGTATCCAACCTGCCGTCTACTCTTGGACAGCCTTCTGAAAGGAAG


ATTAATACAAGATGGCATCATGAGTTCACATGTTCACATGATTAAAGGTATTCCGGT


AGACGATGGGGATGCGTTCCATTAGATAGTAGGGGGGGTAACGGCCCACCTAGTCT


TCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTC


CAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGAGAGCCTGA


ACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATAAA


GGAATAAAGTCGGGTATGCATACCCGTTTGCATGTACTTTATGAATAAGGATCGGCT


AACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTAT


TGGGTTTAAAGGGAGCGTAGATGGATGTTTAAGTCAGTTGTGAAAGTTTGCGGCTC


AACCGTAAAATTGCAGTTGATACTGGATATCTTGAGTGCAGTTGAGGCAGGCGGAA


TTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGC


AGCCTGCTAAGCTGCAACTGACATTGAGGCTCGAAAGTGTGGGTATCAAACAGGAT


TAGATACCCTGGTAGTCCACACGGTAAACGATGAATACTCGCTGTTTGCGATATACG


GCAAGCGGCCAAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACG


GTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAA


TTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAGATGAATTACGGTGA


AAGCCGTAAGCCGCAAGGCATCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTG


CCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTGTTGTCAGTTACTA


ACAGGTTCCGCTGAGGACTCTGACAAGACTGCCATCGTAAGATGTGAGGAAGGTGG


GGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATG


GGGGGTACAGAGGGCCGCTACCACGCGAGTGGATGCCAATCCCAAAAACCTCTCT


CAGTTCGGACTGGAGTCTGCAACCCGACTCCACGAAGCTGGATTCGCTAGTAATCG


CGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTC


AAGCCATGGGAGCCGGGGGTACCTGAAGTGCGTAACCGCGAGGAGCGCCCTAGG


GTAAAACTGGTGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAG





SEQ ID NO: 55 Bifidobacterium adolescentis


GGGCTCGTAGKCGGTTCGTCGCGTCCGGTGTGAAAGTCCAYCGCTTAACGGTGGA


TCCGCGCCGGGTACGGGCGGGCTTGAGTGCGGTAGGGGAGACTGGAATTCCCGGT


GTAACGGTGGAATGTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCT


GGGCCGTCACTGACGCTGAGGAGCGAAAGCGTGGGGAGCGAACAGGATTAGATAC


CCTGGTAGTCCACGCCGTAAACGGTGGATGCTGGATGTGGGGACCATTCCACGGT


CTCCGTGTCGGAGCCAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGG


CTAAAACTCAAAGAAATTGACGGGGGCCCGCACAAGCGGCGGAGCATGCGGATTA


ATTCGATGCAACGCGAAGAACCTTACCTGGGCTTGACATGTTCCCGACAGCCCCAG


AGATGGGGCCTCCCTTCGGGGGGGGTTCACAGGTGGTGCATGGTCGTCGTCAGCT


CGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTCGCCCTGTGTT


GCCAGCACGTCGTGGTGGGAACTCACGGGGGACCGCCGGGGTCAACTCGGAGGA


AGGTGGGGATGACGTCAGATCATCATGCCCCTTACGTCCAGGGCTTCACGCATGCT


ACAATGGCCGGTACAACGGGATGCGACACT-


GTGAGGTGGAGCGGATCCCTTAAAACCGGTCTCAGTTCGGATTGGAGTCTGCAACC


CGACTCCATGAAGGCGGAGTCGCTAGTAATCGCGGATCAGCAACGCCGCGGTGAA


TGCGTTCCCGGGCCTTGTACACACCGCCCGTCAAGTCATGAAAGTGGGTAGCACCC


GAAGCCGGTGGCCCATCCTTTTTGGGG





SEQ ID NO: 56 Bifidobacterium longum


TGGCTCAGGATGAACGCTGGGGGCGTGCTTAACACATGCAAGTCGAACGGGATCC


ATCAGGCTTTGCTTGGTGGTGAGAGTGGCGAACGGGTGAGTAATGCGTGACCGAC


CTGCCCCATACACCGGAATAGCTCCTGGAAACGGGTGGTAATGCCGGATGCTCCAG


TTGATCGCATGGTCTTCTGGGAAAGCTTTCGCGGTATGGGATGGGGTCGCGTCCTA


TCAGCTTGACGGGGGGGTAACGGCCCACCGTGGCTTCGACGGGTAGCCGGCCTGA


GAGGGCGACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGGAGGCA


GCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAGCGACGCCGCGTGAG


GGATGGAGGCCTTCGGGTTGTAAACCTCTTTTATCGGGGAGCAAGCGAGAGTGAGT


TTACCCGTTGAATAAGCACCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAG


GGTGCAAGCGTTATCCGGAATTATTGGGCGTAAAGGGCTCGTAGGCGGTTCGTCGC


GTCCGGTGTGAAAGTCCATCGCTTAACGGTGGATCCGCGCCGGGTACGGGGGGGC


TTGAGTGCGGTAGGGGAGACTGGAATTCCCGGTGTAACGGTGGAATGTGTAGATAT


CGGGAAGAACACCAATGGCGAAGGCAGGTCTCTGGGCCGTTACTGACGCTGAGGA


GCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAAC


GGTGGATGCTGGATGTGGGGCCCGTTCCACGGGTTCCGTGTCGGAGCTAACGCGT


TAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGAAATTGACGG


GGGCCCGCACAAGCGGCGGAGCATGCGGATTAATTCGATGCAACGCGAAGAACCT


TACCTGGGCTTGACATGTTCCCGACGGTCGTAGAGATACGGCTTCCCTTCGGGGCG


GGTTCACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAG


TCCCGCAACGAGCGCAACCCTCGCCCCGTGTTGCCAGCGGATTATGCCGGGAACT


CACGGGGGACCGCCGGGGTTAACTCGGAGGAAGGTGGGGATGACGTCAGATCATC


ATGCCCCTTACGTCCAGGGCTTCACGCATGCTACAATGGCCGGTACAACGGGATGC


GACGCGGCGACGCGGAGCGGATCCCTGAAAACCGGTCTCAGTTCGGATCGCAGTC


TGCAACTCGACTGCGTGAAGGCGGAGTCGCTAGTAATCGCGAATCAGCAACGTCGC


GGTGAATGCGTTCCCGGGCCTTGTACACACCGCCCGTCAAGTCATGAAAGTGGGCA


GCACCCGAAGCCGGTGGCCTAACCCCTTGTGGGATGGAGCCGTCTAAGGTGAGGC


TCGTGATTGGGACTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGG





SEQ ID NO: 57 Bifidobacterium pseudocatenulatum


GGTTCGTCGCGTCCGGTGTGAAAGTCCATCGTTTAACGGTGGATCTGCGCCGGGTA


CGGGGGGGCTGGAGTGCGGTAGGGGAGACTGGAATTCCCGGTGTAACGGTGGAAT


GTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCTGGGCCGTTACTGA


CGCTGAGGAGCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCAC


GCCGTAAACGGTGGATGCTGGATGTGGGGCCCGTTCCACGGGTTCCGTGWCGGAG


CTAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACWMAAAK


AAATTGACGGGGGCCCGCACAAGCGGCGGAGCATGCGGATTAATTCGATGCAACG


CGAAGAACCTTACCTGGGCTTGACATGTTCCCGACAGCCGTAGAGATATGGCCTCC


CTTCGGGGGGGGTTCACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGAGAT


GTTGGGTTAAGTCCCGCAACGAGCGCAACCCTCGCCCTGTGTTGCCAGCACGTCAT


GGTGGGAACTCACGGGGGACCGCCGGGGTCAACTCGGAGGAAGGTGGGGATGAC


GTCAGATCATCATGCCCCTTACGTTCAGGGCTTCACGCATGCTACAATGGCCGGTA


CAACGGGATGCGACACGGCGACGTG





SEQ ID NO: 58 Blautia coccoides/ Blautia producta


TGTGACTGAGCGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCTCATACAGGG


GGATAACAGTTAGAAATGACTGCTAATACCGCATAAGCGCACAGGACCGCATGGTC


TGGTGTGAAAAACTCCGGTGGTATGAGATGGACCCGCGTCTGATTAGCTAGTTGGA


GGGGTAACGGCCCACCAAGGCGACGATCAGTAGCCGGCCTGAGAGGGTGAACGG


CCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAAT


ATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCT


CGGTATGTAAACTTCTATCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCC


CCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCG


GATTTACTGGGTGTAAAGGGAGCGTAGACGGAAGAGCAAGTCTGATGTGAAAGGCT


GGGGCTTAACCCCAGGACTGCATTGGAAACTGTTGTTCTAGAGTGCCGGAGAGGTA


AGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGG


CGAAGGCGGCTTACTGGACGGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCA


AACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGG


GTGGCAAAGCCATTCGGTGCCGCAGCAAACGCAATAAGTATTCCACCTGGGGAGTA


CGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAG


CATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCCTCTG


ACCGTCCCGTAACGGGGGCTTCCCTTCGGGGCAGAGGAGACAGGTGGTGCATGGT


TGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCT


TATCCTTAGTAGCCAGCACATGATGGTGGGCACTCTAGGGAGACTGCCGGGGATAA


CCCGGAGGAAGGCGGGGACGACGTCAAATCATCATGCCCCTTATGATTTGGGCTAC


ACACGTGCTACAATGGCGTAAACAAAGGGAAGCGAGACAGCGATGTTGAGCGAATC


CCAAAAATAACGTCCCAGTTCGGACTGCAGTCTGCAACTCGACTGCACGAAGCTGG


AATCGCTAGTAATCGCGGATCAGAATGCCGCGGTGAATACGTTCCCGGGTCTTGTA


CACACCGCCCGTCACACCATGGGAGTCAGTAACGCCCGAAGTCAGTGACCTAACC


GAAAGGAAGGAGCTGCCGAAGGGGGGACCGATAACTGGGGTGAAGTCGTAACAAG


GTA





SEQ ID NO: 59 Clostridium citroniae


TCCGGATTTACTGGAGTAGT-


AAGGGAGCGTAGACGGCGAAGCAAGTCTGGAGTGAAAACCCAGGGCTCAACCCTG


GGACTGCTTTGGAAACTGTTTTGCTAGAGTGTCGGAGAGGTAAGTGGAATTCCTAG


TGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGGGCTTAC


TGGACGATAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATAC


CCTGGTAGTCCACGCCGTAAACGATGAATGCTAGGTGTTGGGGGGCAAAGCCCTTC


GGTGCCGTCGCAAACGCAATAAGCATTCCACCTGGGGAGTACGTTCGCAAGAATGA


AACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCG


AAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCCCCTGACCGGTCAGTAAAGT


GACCTTTCCTTCGGGACAGGGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGT


CGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTAGTAGCCAG


CAGGTAAAGCTGGGCACTCTAGGGAGACTGCCAGGGATAACCTGGAGGAAGGTGG


GGATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGG


CGTAAACAAAGGGAAGCGACCCTGCGAAGGCAAGCAAATCCCAAAAATAACGTCCC


AGTTCGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGC


GAATCAGAATGTCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACA


CCATGGGAGTCAGCAACGCCCGAAGTCAGTGACCCAACCGAAAGGAGGGAGCTGC


CGAA





SEQ ID NO: 60 Clostridium clostridioforme


TAATACCGCATAAGCGCACAGTGCCGCATGGCAGTGTGTGAAAAACTCCGGTGGTG


TGAGATGGATCCGCGTCTGATTAGCCAGTTGGGGGGGTAACGGCCCACCAAAGCG


ACGATCAGTAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGC


CCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGAAAGCCTG


ATGCAGCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAAAGCTCTATCAGCA


GGGAAGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAG


CCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAG


CGTAGACGGCGAAGCAAGTCTGAAGTGAAAACCCGGGGCTCAACCCTGGGACTGC


TTTGGAAACTGTTTTGCTAGAGTGTCGGAGAGGTAAGTGGAATTCCTAGTGTAGCG


GTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACGA


TAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTA


GTCCACGCCGTAAACGATGAATGCTAGGTGTTGGGGGGCAAAGCCCTTCGGTGCC


GCCGCAAACGCAGTAAGCATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCA


AAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAA


CGCGAAGAACCTTACCAAGTCTTGACATCCCCCTGACGGGCCGGTAACGCGGCCTT


TCCTTCGGGACAGGGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGA


GATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTAGTAGCCAGCAGGT


AGAGCCGGGCACTCTAGGGAGACTGCCAGGGATAACCTGGAGGAAGGTGGGGATG


ACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGGCGTAA


ACAAAGGGAAGCGAGACAGTGATGTGGAGCAAATCCCAAAAATAACGTCCCAGTTC


GGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGCGAATC


AGAATGTCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATG


GGAGTCAGCAACGCCCGAAGTCAGTGACCCAACCGAAAGGAGGGAGCTGCCGAAG


GCGGGGCAGGTAACTGGGGTGAAGTCGT





SEQ ID NO: 61 Clostridium innocuum


ATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCATGCCTAATACATGCA


AGTCGAACGAAGT-


TTCGAGGAAGCTTGCTTCCAAAGAGACTTAGTGGCGAACGGGTGAGTAACACGTAG


GTAACCTGCCCATGTGTCCGGGATAACTGCTGGAAACGGTAGCTAAAACCGGATAG


GTATACAGAGCGCATGCTCAGTATATTAAAGCGCCCATCAAGGCGTGAACATGGAT


GGACCTGCGGCGCATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGATGATG


CGTAGCCGGCCTGAGAGGGTAAACGGCCACATTGGGACTGAGACACGGCCCAAAC


TCCTACGGGAGGCAGCAGTAGGGAATTTTCGTCAATGGGGGAAACCCTGAACGAG


CAATGCCGCGTGAGTGAAGAAGGTCTTCGGATCGTAAAGCTCTGTTGTAAGTGAAG


AACGGCTCATAGAGGAAATGCTATGGGAGTGACGGTAGCTTACCAGAAAGCCACGG


CTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGAATC


ATTGGGCGTAAAGGGTGCGTAGGTGGCGTACTAAGTCTGTAGTAAAAGGCAATGGC


TCAACCATTGTAAGCTATGGAAACTGGTATGCTGGAGTGCAGAAGAGGGCGATGGA


ATTCCATGTGTAGCGGTAAAATGCGTAGATATATGGAGGAACACCAGTGGCGAAGG


CGGTCGCCTGGTCTGTAACTGACACTGAGGCACGAAAGCGTGGGGAGCAAATAGG


ATTAGATACCCTAGTAGTCCACGCCGTAAACGATGAGAACTAAGTGTTGGAGGAATT


CAGTGCTGCAGTTAACGCAATAAGTTCTCCGCCTGGGGAGTATGCACGCAAGTGTG


AAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTC


GAAGCAACGCGAAGAACCTTACCAGGCCTTGACATGGAAACAAATACCCTAGAGAT


AGGGGGATAATTATGGATCACACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGT


GAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTCGCATGTTACCAGCAT


CAAGTTGGGGACTCATGCGAGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATG


ACGTCAAATCATCATGCCCCTTATGGCCTGGGCTACACACGTACTACAATGGCGGC


CACAAAGAGCAGCGACACAGTGATGTGAAGCGAATCTCATAAAGGTCGTCTCAGTT


CGGATTGAAGTCTGCAACTCGACTTCATGAAGTCGGAATCGCTAGTAATCGCAGAT


CAGCATGCTGCGGTGAATACGTTCTCGGGCCTTGTACACACCGCCCGTCAAACCAT


GGGAGTCAGTAATACCCGAAGCCGGTGGCATAACCGTAAGGAGTGAGCCGTCGAA


GGTAGGACCGA





SEQ ID NO: 62 Clostridium innocuum / Erysipelotrichaceae bacterium 6_1_45


ATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGGGGCATGCCTAATACATGCA


AGTCGAACGAAGT-


TTCGAGGAAGCTTGCTTCCAAAGAGACTTAGTGGCGAACGGGTGAGTAACACGTAG


GTAACCTGCCCATGTGTCCGGGATAACTGCTGGAAACGGTAGCTAAAACCGGATAG


GTATACAGAGCGCATGCTCAGTATATTAAAGCGCCCATCAAGGCGTGAACATGGAT


GGACCTGCGGCGCATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGATGATG


CGTAGCCGGCCTGAGAGGGTAAACGGCCACATTGGGACTGAGACACGGCCCAAAC


TCCTACGGGAGGCAGCAGTAGGGAATTTTCGTCAATGGGGGAAACCCTGAACGAG


CAATGCCGCGTGAGTGAAGAAGGTCTTCGGATCGTAAAGCTCTGTTGTAAGTGAAG


AACGGCTCATAGAGGAAATGCTATGGGAGTGACGGTAGCTTACCAGAAAGCCACGG


CTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGAATC


ATTGGGCGTAAAGGGTGCGTAGGTGGCGTACTAAGTCTGTAGTAAAAGGCAATGGC


TCAACCATTGTAAGCTATGGAAACTGGTATGCTGGAGTGCAGAAGAGGGCGATGGA


ATTCCATGTGTAGCGGTAAAATGCGTAGATATATGGAGGAACACCAGTGGCGAAGG


CGGTCGCCTGGTCTGTAACTGACACTGAGGCACGAAAGCGTGGGGAGCAAATAGG


ATTAGATACCCTAGTAGTCCACGCCGTAAACGATGAGAACTAAGTGTTGGAGGAATT


CAGTGCTGCAGTTAACGCAATAAGTTCTCCGCCTGGGGAGTATGCACGCAAGTGTG


AAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTC


GAAGCAACGCGAAGAACCTTACCAGGCCTTGACATGGAAACAAATACCCTAGAGAT


AGGGGGATAATTATGGATCACACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGT


GAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTCGCATGTTACCAGCAT


CAAGTTGGGGACTCATGCGAGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATG


ACGTCAAATCATCATGCCCCTTATGGCCTGGGCTACACACGTACTACAATGGCGAC


CACAAAGAGCAGCGACACAGTGATGTGAAGCGAATCTCATAAAGGTCGTCTCAGTT


CGGATTGAAGTCTGCAACTCGACTTCATGAAGTCGGAATCGCTAGTAATCGCAGAT


CAGCATGCTGCGGTGAATACGTTCTCGGGCCTTGTACACACCGCCCGTCAAACCAT


GGGAGTCAGTAATACCCGAAGCCGGTGGCATAACCGTAAGGAGTGAGCCGTCGAA


GGTAGGACCGA





SEQ ID NO: 63 Clostridium sordellii


ACACATGCAAGTCGAGCGAACCCTTCGGGGTGAGCGGCGGACGGGTGAGTAACGC


GTGGGTAACCTGCCCTGTACACACGGATAACATACCGAAAGGTATGCTAATACGGG


ATRAYATATGAGAGTCGCATGGCTTTTGTATCAAAGCTCCGGCGGTACAGGATGGA


CCCGCGTCTGATTAGCTAGTTGGTAAGGTAACGGCTTACCAAGGCAACGATCAGTA


GCCGACCTGAGAGGGTGATCGGCCACATTGGAACTGAGACACGGTCCAAACTCMT


ACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGAAAGCCTGATGCAGCAAC


GCCGCGTGAGCGATGAAGGCCTTCGGGTCGTAAAGCTCTGTCCTCAAGGAAGATAA


TGACGGTACTTGAGGAGGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAAT


ACGTAGGGGGCTAGCGTTATCCGGAATTACTGGGCGTAAAGGGTGCGTAGGCGGT


CTTTCAAGCCAGAAGTGAAAGGCTACGGCTCAACCGTAGTAAGCTTTTGGAACTGT


AGGACTTGAGTGCAGGAGAGGAGAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTA


GATATTAGGAGGAACACCAGTAGCGAAGGCGGCTCTCTGGACTGTAACTGACGCTG


AGGCACGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGT


AAACGATGAGTACTAGGTGTCGGGGGTTACCCCCCTCGGTGCCGCAGCTAACGCAT


TAAGTACTCCGCCTGGGAAGTACGCTCGCAAGAGTGAAACTCAAAGGAATTGACGG


GGACCCGCACAAGTAGCGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTT


ATCTAARCTTGACATC





SEQ ID NO: 64 Coprococcus comes


ACRGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGAC


GCCRCGTGAGCGAAGAAGTATTKCGGTATGTAAAGCTCTATCAGCAGGGAAGAAAA


TGACGGTACCTGACTAAGAAGCACCGGCTAAATACGTGCCAGCAGCCGCGGTAATA


CGTATGGTGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGCTG


TGTAAGTCTGAAGTGAAAGGGGGGGGCTCCCCCCCGGGGACTGCTTTGGAAACTAT


GCAGCTAGACTGTCGGACAGGTAAGTGGAATTCCCAGTGTAGCGGTGAAATGCGTA


GATATTGGGAGGAACAGCAKTGGGTAAGGCTSCTTACAGGACRAT





SEQ ID NO: 65 Dorea longicatena


TAACGCGTGGGTAACCTGCCTCATACAGGGGGATAACAGTTAGAAATGACTGCTAA


TACCGCATAAGACCACGGTACCGCATGGTACAGTGGTAAAAACTCCGGTGGTATGA


GATGGACCCGCGTCTGATTAGGTAGTTGGTGGGGTAACGGCCTACCAAGCCGACG


ATCAGTAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGCCCA


GACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGAGGAAACTCTGATGC


AGCGACGCCGCGTGAAGGATGAAGTATTTCGGTATGTAAACTTCTATCAGCAGGGA


AGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGC


GGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAG


ACGGCACGGCAAGCCAGATGTG-


AAAGCCCGGGGCTCAACCCCGGGACTGCATTTGGAACTGCTGAGCTAGAGTGTCG


GAGAGGCAAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAAC


ACCAGTGGCGAAGGCGGCTTGCTGGACGATGACTGACGTTGAGGCTCGAAAGCGT


GGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGACTGCTA


GGTGTCGGGTGGCAAAGCCATTCGGTGCCGCAGCTAACGCAATAAGCAGTCCACC


TGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAG


CGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCTGATCTTGAC


ATCCCGATGACCGCTTCGTAATGGAAGCTTTTCTTCGGAACATCGGTGACAGGTGG


TGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGC


GCAACCCCTATCTTCAGTAGCCAGCAGGTTAAGCTGGGCACTCTGGAGAGACTGCC


AGGGATAACCTGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACC


AGGGCTACACACGTGCTACAATGGCGTAAACAAAGAGAAGCGAACTCGCGAGGGTA


AGCAAATCTCAAAAATAACGTCTCAGTTCGGATTGTAGTCTGCAACTCGACTACATG


AAGCTGGAATCGCTAGTAATCGCAGATCAGAATGCTGCGGTGAATACGTTCCCGGG


TCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACGCCCGAAGTCAGTGAC


CCAACCGTAAGG





SEQ ID NO: 66 Erysipelatoclostridium ramosum


GAGGGAGCAGGCGGCAGCAAGGGTCTGTGGTGAAAGCCTGAAGTTAAACTTCAGT


AAGCCATAGAAACCAGGCAGCTAGAGTGCAGGAGAGGAKCGTGGAATTCCATGTGT


AGCGGTGAAATGCGTAGATATATGGAGGAACACCAGTGGCGAAGGCGACGATCTG


GCCTGCAACTGACGCTCAGTCCCGAAAGCGTGGGGAGCAAATAGGATTAGATACCC


TAGTAGTCCACGCCGTAAACGATGAGTACTRAGTGTTGGATGTCAAAGTTCAGTGCT


GCAGTTAACGCAATAAGTACTCCGCCTGAGTAGTACGTTCGCAAGAATGAAACTCAA


AGGAATTGACGGGGGCCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAA


CGCGAAGAACCTTACCAGGTCTTGACATACTCATAAAGGCTCCAGAGATGGAGAGA


TAGCTATATGAGATACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGT


TGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCGTTAGTTACCATCATTAAGTTGG


GGACTCTAGCGAGACTGCCAGTGACAAGCTGGAGGAARGCGGGGATGACGTCAAA


TCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGATGGTGCAGAGG


GAAGCGAAGCCGCGAGGTGAAGCAAAACCCATAAAACCATTCTCAGTTCGGATTGT


AGTCTGCARCTCGACTACATGAAGTTGGAATCGCTAGTAATCGCGAATCARCATGTC


GCGATGAATAMGTTCTCGGGCCTT





SEQ ID NO: 67 Eubacterium rectale


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTC


GAACGAAGCACTTTATTTGATTTCCTTCGGGACTGATTATTTTGTGACTGAGTGGCG


GACGGGTGAGTAACGCGTGGGTAACCTGCCTTGTACAGGGGGATAACAGTTGGAA


ACGGCTGCTAATACCGCATAAGCGCACGGCATCGCATGATGCAGTGTGAAAAACTC


CGGTGGTATAAGATGGACCCGCGTTGGATTAGCTAGTTGGTGAGGTAACGGCCCAC


CAAGGCGACGATCCATAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAG


ACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGA


AAGCCTGATGCAGCGACGCCGCGTGAGCGAAGAAGTATTTCGGTATGTAAAGCTCT


ATCAGCAGGGAAGATAATGACGGTACCTGACTAAGAAGCACCGGCTAAATACGTGC


CAGCAGCCGCGGTAATACGTATGGTGCAAGCGTTATCCGGATTTACTGGGTGTAAA


GGGAGCGCAGGCGGTGCGGCAAGTCTGATGTGAAAGCCCGGGGCTCAACCCCGG


TACTGCATTGGAAACTGTCGTACTAGAGTGTCGGAGGGGTAAGCGGAATTCCTAGT


GTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACT


GGACGATAACTGACGCTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATAC


CCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTTGGGAAGCATTGCTTCTC


GGTGCCGTCGCAAACGCAGTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGA


AACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCG


AAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCTTCTGACCGGTACTTAACCGT


ACCTTCTCTTCGGAGCAGGAGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTC


GTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCTTTAGTAGCCAGC


GGTTCGGCCGGGCACTCTAGAGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGG


ATGACGTCAAATCATCATGCCCCTTATGACTTGGGCTACACACGTGCTACAATGGC


GTAAACAAAGGGAAGCAAAGCTGTGAAGCCGAGCAAATCTCAAAAATAACGTCTCA


GTTCGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGCA


GATCAGAATGCTGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACAC


CATGGGAGTTGGGAATGCCCGAAGCCAGTGACCTAACCGAAAGGAAGGAGCTGTC


GAAGGCAGGCTCGATAACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGG


TGCGGCTGGATCACCT





SEQ ID NO: 68 Odoribacter splanchnicus


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCTTAACACATGCAAGTC


GAGGGGCATCATGAGGTAGCAATACCTTGATGGCGACCGGCGCACGGGTGAGTAA


CGCGTATGCAACCTGCCCGATACCGGGGTATAGCCCATGGAAACGTGGATTAACAC


CCCATAGTACTTTTATCCTGCATGGGATGTGAGTTAAATGTTTAAGGTATCGGATGG


GCATGCGTCCTATTAGTTAGTTGGCGGGGTAACAGCCCACCAAGACGATGATAGGT


AGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCT


ACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAA


GTCGCGTGAGGGAAGACTGCCCTATGGGTTGTAAACCTCTTTTATAAGGGAAGAAT


AAGTTCTACGTGTAGAATGATGCCTGTACCTTATGAATAAGCATCGGCTAACTCCGT


GCCAGCAGCCGCGGTAATACGGAGGATGCGAGCGTTATCCGGATTTATTGGGTTTA


AAGGGTGCGTAGGCGGTTTATTAAGTTAGTGGTTAAATATTTGAGCTAAACTCAATT


GTGCCATTAATACTGGTAAACTGGAGTACAGACGAGGTAGGCGGAATAAGTTAAGT


AGCGGTGAAATGCATAGATATAACTTAGAACTCCGATAGCGAAGGCAGCTTACCAG


ACTGTAACTGACGCTGATGCACGAGAGCGTGGGTAGCGAACAGGATTAGATACCCT


GGTAGTCCACGCCGTAAACGATGCTCACTGGTTCTGTGCGATATATTGTACGGGAT


TAAGCGAAAGTATTAAGTGAGCCACCTGGGGAGTACGTCGGCAACGATGAAACTCA


AAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATA


CGCGAGGAACCTTACCTGGGTTTAAATGGGAAATGTCGTATTTGGAAACAGATATTC


TCTTCGGAGCGTTTTTCAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGT


GTCGGGTTAAGTCCCATAACGAGCGCAACCCTTACCGTTAGTTGCTAGCATGTAAT


GATGAGCACTCTAACGGGACTGCCACCGTAAGGTGAGAGGAAGGCGGGGATGACG


TCAAATCAGCACGGCCCTTACACCCAGGGCTACACACGTGTTACAATGGCCGGTAC


AGAGGGCCGCTACCAGGTGACTGGATGCCAATCTCAAAAGCCGGTCGTAGTTCGG


ATTGGAGTCTGTAACCCGACTCCATGAAGTTGGATTCGCTAGTAATCGCGCATCAG


CCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATG


GAAGCCGGGGGTGCCTGAAGTCCGTAACCGCGAGGATCGGCCTAGGGCAAAACTG


GTAACTGGGGCTAAGTCGTAACAAGGTA





SEQ ID NO: 69 Parabacteroides distasonis


CGAGGGGCAGCRCAGGAGT-TAGCAATAC-


CSGGTGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACTTRCCTATCAGAGG


GGGATAACCCGGCGAAAGTCGGACTAATACCGCATGAAGCAGGGATYCCGCATGG


GRATATTTGCTAAAGATTCATCGCTGATAGATAGGCATGCGTTCCATTAGGCAGTTG


GCGGGGTAACRGCCCACCAAACCGACGATGGATAGGGGTTCTGAGAGGAAGGTCC


CCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAAT


ATTGGTCAATGGSCGWRAGSCTGAACCAGCCAAGTCGCGTGAGGGATGAAGGTTC


TATGGATCGTAAACCTCTTTTATAAGGGAATAAAGTGCGGGACGTGTCCYRTTTTGT


ATGTACCTTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGG


AGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCCTTTT


AAGTCAGCGGTGAAAGTCTGTGGCTCAACCATAGAATTGCCGTTGAAACTGGGGGG


CTTGAGTATGTTTGAGGCAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATA


TCACGCAGAACCCCGWTTGCGAAGGCAGCCTGCCAAGCCGTAACTGACGCGGATG


CACGAAAGCGTGGGGATCAAACAGGATTAGATACCCTGGTA





SEQ ID NO: 70 Parabacteroides merdae


CATGCAAGTCGAGGGGCAGCATGATTTGTAGCAATACAGATTGATGGCGACCGGCG


CACGGGTGAGTAACGCGTATGCAACTTACCTATCAGAGGGGGATAGCCCGGCGAA


AGTCGGATTAATACCCCATAAAACAGGGGTCCCGCATGGGAATATTTGTTAAAGATT


CATCGCTGATAGATAGGCATGCGTTCCATTAGGCAGTTGGCGGGGTAACGGCCCAC


CAAACCGACGATGGATAGGGGTTCKGAGAGGAAGGTCCCCCACATTGGTACTGAGA


CACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGCCGAG


AGGCTGAACCAGCCAAGTCGCGTGAAGGAAGAAGGATCTATGGTTTGTAAACTTCT


TTTATAGGGGAATAAAGTGGAGGACGTGTCCTTTTTTGTATGTACCCTATGAATAAG


CATCGGCTAACTCCGTGMSARCMGCCGCGGGAATACGGAAGATGCAGAGCGTTAT


CCGGATWTATTGGGGTTA





SEQ ID NO: 71 Bacteroides xylanisolvens


CATGCAAGTCGAGGGGCAGCATTTTAGTTTGCTTGCAAACTAAAGATGGCGACCGG


CGCACGGGTGAGTAACACGTATCCAACCTGCCGATAACTCGGGGATAGCCTTTCGA


AAGAAAGATTAATATCCGATAGTATATTAAAACCGCATGGTTTTACTATTAAAGAATT


TCGGTTATCGATGGGGATGCGTTCCATTAGTTTGTTGGCGGGGTAACGGCCCACCA


AGACTACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACA


CGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGT


CTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTA


TATGGGAATAAAGTATTCCACGTGTGGGATTTTGTATGTACCATATGAATAAGGATC


GGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGA


TTTATTGGGTTTAAAGGGAGCGTAGGTGGATTGTTAAGTCAGTTGTGAAAGTTTGCG


GCTCAACCGTAAAATTGCAGTTGAAACTGGCAGTCTTGAGTACAGTAGAGGTGGGC


GGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGA


AGGCAGCTCACTAGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATCAAACA


GGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATA


TACAGTAAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCA


ACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGT


TTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCATTTGAATAATCT


GGAAACAGGTTAGCCGCAAGGCAAATGTGAAGGTGCTGCATGGTTGTCGTCAGCTC


GTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTA


CTAACAGGTTATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGG


TGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACA


ATGGGGGGTACAGAAGGCAGCTACCTGGCGACAGGATGCTAATCCCAAAAACCTCT


CTCAGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAAT


CGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCG


TCAAGCCATGAAAGCCGGGG





SEQ ID NO: 72 Blautia obeum


GGCGTGCTTAACACATGCAAGTCGAACGGGAAACCTTTTATTGAAGCTTCGGCAGA


TTTAG-


CTGGTTTCTAGTGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCTTATACAGGG


GGATAACAACCAGAAATGGTTGCTAATACCGCATAAGCGCACAGGACCGCATGGTC


CGGTGTGAAAAACTCCGGTGGTATAAGATGGACCCGCGTTGGATTAGCTAGTTGGC


AGGGTAACGGCCTACCAAGGCGACGATCCATAGCCGGCCTGAGAGGGTGAACGGC


CACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATA


TTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATCT


CGGTATGTAAACTTCTATCAGCAGGGAAGATAGTGACGGTACCTGACTAAGAAGCC


CCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCG


GATTTACTGGGTGTAAAGGGAGCGTAGACGGACTGGCAAGTCTGATGTGAAAGGCG


GGGGCTCAACCCCTGGACTGCATTGGAAACTGTTAGTCTTGAGTGCCGGAGAGGTA


AGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGG


CGAAGGCGGCTTACTGGACGGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCA


AACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTTGG


GGAGCAAAGCTCTTCGGTGCCGCCGCAAACGCATTAAGTATTCCACCTGGGGAGTA


CGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAG


CATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCCTCTG


ACCGTTCCTTAACCGGAACTTTCCTTCGGGACAGGGGAGACAGGTGGTGCATGGTT


GTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCT


ATCCCCAGTAGCCAGCAGTCCGGCTGGGCACTCTGAGGAGACTGCCAGGGATAAC


CTGGAGGAAGGCGGGGATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACA


CACGTGCTACAATGGCGTAAACAAAGGGAAGCAAGCCTGCGAAGGTAAGCAAATCC


CAAAAATAACGTCCCAGTTCGGACTGCAGTCTGCAACTCGACTGCACGAAGCTGGA


ATCGCTAGTAATCGCGGATCAGAATGCCGCGGTGAATACGTTCCCGGGTCTTGTAC


ACACCGCCCGTCACACCATGGGAGTCAGTAACGCCCGAAGTCAGTGACCTAACTGC





SEQ ID NO: 73 Alistipes putredinis


AGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGGCAGGCTTAACACATGCAAGTC


GAGGGGCAGCATAATGGATAGCAATATCTATGGTGGCGACCGGCGCACGGGTGCG


TAACGCGTATGCAACCTACCTTTAACAGGGGGATAACACTGAGAAATTGGTACTAAT


ACCCCATAATATCATAGAAGGCATCTTTTATGGTTGAAAATTCCGATGGTTAGAGAT


GGGCATGCGTTGTATTAGCTAGTTGGTGGGGTAACGGCTCACCAAGGCGACGATAC


ATAGGGGGACTGAGAGGTTAACCCCCCACACTGGTACTGAGACACGGACCAGACT


CCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGCAAGTCTGAACCAGC


CATGCCGCGTGCAGGATGACGGCTCTATGAGTTGTAAACTGCTTTTGTACGAGGGT


AAACGCAGATACGTGTATCTGTCTGAAAGTATCGTACGAATAAGGATCGGCTAACTC


CGTGCCAGCAGCCGCGGTAATACGGAGGATTCAAGCGTTATCCGGATTTATTGGGT


TTAAAGGGTGCGTAGGCGGTTTGATAAGTTAGAGGTGAAATTTCGGGGCTCAACCC


TGAACGTGCCTCTAATACTGTTGAGCTAGAGAGTAGTTGCGGTAGGCGGAATGTAT


GGTGTAGCGGTGAAATGCTTAGAGATCATACAGAACACCGATTGCGAAGGCAGCTT


ACCAAACTATATCTGACGTTGAGGCACGAAAGCGTGGGGAGCAAACAGGATTAGAT


ACCCTGGTAGTCCACGCAGTAAACGATGATAACTCGTTGTCGGCGATACACAGTCG


GTGACTAAGCGAAAGCGATAAGTTATCCACCTGGGGAGTACGTTCGCAAGAATGAA


ACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGA


TGATACGCGAGGAACCTTACCCGGGCTTGAAAGTTAGCGACGATTCTTGAAAGAGG


ATTTCCCTTCGGGGCGCGAAACTAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGT


GAGGTGTCGGGTTAAGTCCCATAACGAGCGCAACCCCTACCGTTAGTTGCCATCAG


GTGAAGCTGGGCACTCTGGGGGGACTGCCGGTGTAAGCCGAGAGGAAGGTGGGG


ATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGT


AGGTACAGAGGGCAGCTACCCAGCGATGGGATGCGAATCTCGAAAGCCTATCTCAG


TTCGGATTGGAGGCTGAAACCCGCCTCCATGAAGTTGGATTCGCTAGTAATCGCGC


ATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAG


CCATGGGAGCCGGGGGTGCCTGAAGTTCGTGACCGCAAGGAGCGACCTAGGGCAA


AACTGGTGACTGGGGCTAAGTCGTAACAAGGTA





SEQ ID NO: 74 Collinsella aerofaciens


AGAGTTCGATCCTGGCTCAGGATGAACGCTGGCGGCGCGCCTAACACATGCAAGT


CGAACGGCACCTATCTTCGGATAGAAGCGAGTGGCGAACGGCTGAGTAACACGTG


GAGAACCTGCCCCCTCCCCCGGGATAGCCGCCCGAAAGGACGGGTAATACCGGAT


ACCCCGGGGTGCCGCATGGCACCCCGGCTAAAGCCCCGACGGGAGGGGATGGCT


CCGCGGCCCATCAGGTAGACGGCGGGGTGACGGCCCACCGTGCCGACAACGGGT


AGCCGGGTTGAGAGACCGACCGGCCAGATTGGGACTGAGACACGGCCCAGACTCC


TACGGGAGGCAGCAGTGGGGAATCTTGCGCAATGGGGGGAACCCTGACGCAGCGA


CGCCGCGTGCGGGACGGAGGCCTTCGGGTCGTAAACCGCTTTCAGCAGGGAAGAG


TCAAGACTGTACCTGCAGAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGT


AATACGTAGGGGGCGAGCGTTATCCGGATTCATTGGGCGTAAAGCGCGCGTAGGC


GGCCCGGCAGGCCGGGGGTCGAAGCGGGGGGCTCAACCCCCCGAAGCCCCCGGA


ACCTCCGCGGCTTGGGTCCGGTAGGGGAGGGTGGAACACCCGGTGTAGCGGTGG


AATGCGCAGATATCGGGTGGAACACCGGTGGCGAAGGCGGCCCTCTGGGCCGAGA


CCGACGCTGAGGCGCGAAAGCTGGGGGAGCGAACAGGATTAGATACCCTGGTAGT


CCCAGCCGTAAACGATGGACGCTAGGTGTGGGGGGACGATCCCCCCGTGCCGCAG


CCAACGCATTAAGCGTCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAG


GAATTGACGGGGGCCCGCACAAGCAGCGGAGCATGTGGCTTAATTCGAAGCAACG


CGAAGAACCTTACCAGGGCTTGACATATGGGTGAAGCGGGGGAGACCCCGTGGCC


GAGAGGAGCCCATACAGGTGGTGCATGGCTGTCGTCAGCTCGTGTCGTGAGATGTT


GGGTTAAGTCCCGCAACGAGCGCAACCCCCGCCGCGTGTTGCCATCGGGTGATGC


CGGGAACCCACGCGGGACCGCCGCCGTCAAGGCGGAGGAGGGGGGGGACGACGT


CAAGTCATCATGCCCCTTATGCCCTGGGCTGCACACGTGCTACAATGGCCGGTACA


GAGGGATGCCACCCCGCGAGGGGGAGCGGATCCCGGAAAGCCGGCCCCAGTTCG


GATTGGGGGCTGCAACCCGCCCCCATGAAGTCGGAGTTGCTAGTAATCGCGGATC


AGCATGCCGCGGTGAATGCGTTCCCGGGCCTTGTACACACCGCCCGTCACACCAC


CCGAGTCGTCTGCACCCGAAGTCGCCGGCCCAACCGAGAGGGGGGAGGCGCCGA


AGGTGTGGAGGGTGAGGGGGGTGAAGTCGTAACAAGGTA





SEQ ID NO: 75 Bacteroides faecis /Eubacterium hallii


CTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATTCC


AGTTTGCTTGCAAACTGGAGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCA


ACCTGCCGATAACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGCAT


AATAGAACCGCATGGTTTGATTATTAAAGAATTTCGGTTATCGATGGGGATGCGTTC


CATTAGGCAGTTGGTGGGGTAACGGCCCACCAAACCTTCGATGGATAGGGGTTCTG


AGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGC


AGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAA


GGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGTGGTCCACGT


GTGGATTTTTGTATGTACCATATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCG


CGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTA


GGTGGACAGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTG


ATACTGGCTGTCTTGAGTACAGTAGAGGGGGGGGAATTCGTGGTGTAGCGGTGAA


ATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGACTGCAACT


GACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCA


CACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAAA


GCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTG


ACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGA


ACCTTACCCGGGCTTAAATTGCATTTGAATATATTGGAAACAGTATAGTCGTAAGAC


AAATGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAA


GTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCATGCTGAGGACTC


TGGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCA


CGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCCGC


TACCTGGTGACAGGATGCTAATCCCAAAAGCCTCTCTCAGTTCGGATCGAAGTCTG


CAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGG


TGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGG


TACCTGAAGTACGTAACCGCAAGGAGCGTCCTAGGGTAAAACTGGTAATTGGGGCT


AAGTCGTAACAAGGTA





SEQ ID NO: 76 Alistipes shahii


ACATAGGGGGWSTGWKAGGTTWRCCSCCCACATTSRTACTGAGMCA-


TGAWCMAACTCTMTACGGGARGSAGSAGTGAGGAATATTGGTCRRTGGACGCAAG


TCTGAACCAGCCATGCCGSGTGCRGGAAGACGGCTCKATGAGTKGKAAACTGCTTT


TGTACRARRGTAAACGCTCTTACGTGTAAGAGCCTGAAAGTATSGTACRAATGAGGA


TCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCAAGCGTTATCCG


GATTTATTGGGTTTAAAGGGTGCGTAGGGGGGTTGATAAAGTTAGRGG





SEQ ID NO: 77 Anaerostipes caccae


GCTT-ACACATG-


CAAGTCGAACGAAGCATTTARGATTGAAGTTTTCGGATGGATTTCCTATATGACTGA


GTGGCGGACGGGTGAGTAACGCGTGGGGAACCTGCCCTATACAGGGGGATAACAG


CTGGAAACGGCTGCTAATACCGCATAAGCGCACAGAATCGCATGATTCAGTGTGAA


AAGCCCTGGCAGTATAGGATGGTCCCGCGTCTGATTAGCTGGTTGGTGAGGTAACG


GCTCACCAAGGCGACGATCAGTAGCCGGCTTGAGAGAGTGAACGGCCACATTGGG


ACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAAT


GGGGG-


AAACCCTGATGCAGCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAAAGCTC


TATCAGCAGGGAAGAAAACAGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGT


GCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGAATTACTGGGTGT


AAAGGGTGCGTAGGTGGCATGGTAAGTCAGAAGTGAAAGCCCGGGGCTTAACCCC


GGGACTGCTTTTGAAACTGTCATGCTGGAGTGCAGGAGAGGTAAGCGGAATTCCTA


GTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTA


CTGGACTGTCACTGACACTGATGCACGAAAGCGTGGGGAGCAAACAGGATTAGATA


CCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGGGCCGTAGAGGCTT


CGGTGCCGCAGCAAA





SEQ ID NO: 78 Phascolarctobacterium faecium


CGGAGAATTTTCATTTCGGTAGAATTCTTAGTGGCGAACGGGTGAGTAACGCGTAG


GCAACCTGCCCTTTAGACGGGGACAACATTCCGAAAGGAGTGCTAATACCGGATGT


GATCATCGTGCCGCATGGCAGGATGAAGAAAGATGGCCTCTACAAGTAAGCTATCG


CTAAAGGATGGGCCTGCGTCTGATTAGCTAGTTGGTAGTGTAACGGACTACCAAGG


CGATGATCAGTAGCCGGTCTGAGAGGATGAACGGCCACATTGGGACTGAGACACG


GCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATCTTCCGCAATGGACGAAAGTC


TGACAGAGCAACGCCGCGTGAGTGATGAAGGATTTCGGTCTGTAAAGCTCTGTTGT


TTATGACGAACGTGCAGTGTGTGAACAATGCATTGCAATGACGGTAGTAAACGAGG


AAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCGAGCGTT


GTCCGGAATTATTGGGCGTAAAGAGCATGTAGGCGGCTTAATAAGTCGAGCGTGAA


AAATGCGGGGCTCAACCCCGTATGGCGCTGGAAACTGTTAGGCTTGAGTGCAGGA


GAGGAAAGGGGAATTCCCAGTGTAGCGGTGAAATGCGTAGATATTGGGAGGAACAC


CAGTGGCGAAGGCGCCTTTCTGGACTGTGTTTGACGCTGAGATGCGAAAGCCAGG


GTAGC





SEQ ID NO: 79 Agathobaculum butyriciproducens


TAGTGGGGGACGGGTGAGTAACGCGTGAGCAATCTGCCTTTAAGAGGGGGATAAC


AGTCGGAAACGGCTGCTAATACCGCATAAAGCATTGAATTCGCATGTTTTCGATGCC


AAAGGAGCAATCCGCTTTTAGATGAGCTCGCGTCTGATTAGCTAGTTGGGGGGTA


ACGGCCCACCAAGGCGACGATCAGTAGCCGGACTGAGAGGTTGAACGGCCACATT


GGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCGC


AATGGGGGRAACCCTGACGCAGCAACGCCGCGTGATTGAAGAAGGCCTTCGGGTT


GTAAAGATCTTTAATCAGGGACGAA--


AMATGACGGTACCTGAAGAATAAGCTCCGGCTAACTACGTGCCAGCAGCCGCGGTA


ATACGTAGGGAGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGCGCGCAGGCG


GGCCGGCAAGTTGGAAGTGAAATCCGGGGGCTTAACCCCCGAACTGCTTTCAAAAC


TGCTGGTCTTGAGTGATGGAGAGGCAGGCGGAATTCCGTGTGTAGCGGTGAAATG


CGTAGATATACGGAGGAACACCAGTGGCGAAGGCGGCCTGCTGGACATTAACTGA


CGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCAC


GCCGTAAACGATGGATA





SEQ ID NO: 80 Bacteroides fragilis


ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCA


AGTCGAGGGGCATCAGGAAGAAAGCTTGCTTTCTTTGCTGGCGACCGGCGCACGG


GTGAGTAACACGTATCCAACCTGCCCTTTACTCGGGGATAGCCTTTCGAAAGAAAG


ATTAATACCCGATGGCATAATGATTCCGCATGGTTTCATTATTAAAGGATTCCGGTA


AAGGATGGGGATGCGTTCCATTAGGTTGTTGGTGAGGTAACGGCTCACCAAGCCTT


CGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTC


CAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGCTAGCCTGAA


CCAGCCAAGTAGCGTGAAGGATGAAGGCTCTATGGGTCGTAAACTTCTTTTATATAA


GAATAAAGTGCAGTATGTATACTGTTTTGTATGTATTATATGAATAAGGATCGGCTAA


CTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTG


GGTTTAAAGGGAGCGTAGGTGGACTGGTAAGTCAGTTGTGAAAGTTTGCGGCTCAA


CCGTAAAATTGCAGTTGATACTGTCAGTCTTGAGTACAGTAGAGGTGGGCGGAATT


CGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAG


CTCACTGGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTA


GATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGT


AAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGT


GAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATT


CGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAGTGGAATGATGTGGAAA


CATGTCAGTGAGCAATCACCGCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTG


CCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAA


CAGGTTATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGG


GGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATG


GGGGGTACAGAAGGCAGCTAGCGGGTGACCGTATGCTAATCCCAAAAGCCTCTCTC


AGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGC


GCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCA


AGCCATGGGAGCCGGGGGTACCTGAAGTACGTAACCGCAAGGATCGTCCTAGGGT


AAAACTGGTGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGC


TGGAACACCTCCTT





SEQ ID NO: 81 Fusobacterium mortiferum


TGGCTCAGGATGAACGCTGACAGAATGCTTAACACATGCAAGTCTACTTGATCCTTC


GGGTGATGGTGGCGGACGGGTGAGTAACGCGTAAAGAACTTGCCCTGCAGTCTGG


GACAACATTTGGAAACGAATGCTAATACCGGATATTATGT-


ATTTCTCGCATGAGTTTTACATGAAAGCTATATGCGCTGCAGGAGAGCTTTGCGTCC


TATTAGCTAGTTGGTGAGGTAACGGCTCACCAAGGCCATGATAGGTAGCCGGCCTG


AGAGGGTGAACGGCCACAAGGGGACTGAGACACGGCCCTTACTCCTACGGGAGGC


AGCAGTGGGGAATATTGGACAATGGACCAAAAGTCTGATCCAGCAATTCTGTGTGC


ACGATGAAGTTTTTCGGAATGTAAAGTGCTTTCAGTTGGGACGAAGTAAGTGACGGT


ACCAACAGAAGAAGCGACGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGT


CGCAAGCGTTATCCGGATTTATTGGGCGTAAAGCGCGTCTAGGCGGTTTGGTAAGT


CTGATGTGAAAATGCGGGGCTCAACTCCGTATTGCGTTGGAAACTGCTAAACTAGA


GTACTGGAGAGGTGGGGGGAACTACAAGTGTAGAGGTGAAATTCGTAGATATTTGT


AGGAATGCCGATGGGGAAGCCAGCCCACTGGACAGATACTGACGCTAAAGCGCGA


AAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGA


TTACTAGGTGTTGGGGGTCGAACCTCAGCGCCCAAGCTAACGCGATAAGTAATCCG


CCTGGGGAGTACGTACGCAAGTATGAAACTCAAAGGAATTGACGGGGACCCGCACA


AGCGGTGGAGCATGTGGTTTAATTCGACGCAACGCGAGGAACCTTACCAGCGTTTG


ACATCCTAAGAAATTAGCAGAGATGCTTTTGTGCCCCTTCGGGGGAACTTAGTGACA


GGTGGTGCATGGCTGTCGTCAGCTCGTGT





SEQ ID NO: 82 Paraclostridium benzoelyticum/ Clostridium bifermantans


AGAGTTTGATCCTGGCTCAGGATGAACGCTGGGGGCGTGCCTAACACATGCAAGTC


GAGCGATCTCTTCGGAGAGAGCGGCGGACGGGTGAGTAACGCGTGGGTAACCTGC


CCTGTACACACGGATAACATACCGAAAGGTATACTAATACGGGATAACATACGAAAG


TCGCATGGCTTTTGTATCAAAGCTCCGGGGGTACAGGATGGACCCGCGTCTGATTA


GCTAGTTGGTAAGGTAATGGCTTACCAAGGCAACGATCAGTAGCCGACCTGAGAGG


GTGATCGGCCACACTGGAACTGAGACACGGTCCAGACTCCTACGGGAGGCAGCAG


TGGGGAATATTGCACAATGGGCGAAAGCCTGATGCAGCAACGCCGCGTGAGCGAT


GAAGGCCTTCGGGTCGTAAAGCTCTGTCCTCAAGGAAGATAATGACGGTACTTGAG


GAGGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCTAG


CGTTATCCGGAATTACTGGGCGTAAAGGGTGCGTAGGTGGTTTTTTAAGTCAGAAG


TGAAAGGCTACGGCTCAACCGTAGTAAGCTTTTGAAACTAGAGAACTTGAGTGCAG


GAGAGGAGAGTAGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAAT


ACCAGTAGCGAAGGCGGCTCTCTGGACTGTAACTGACACTGAGGCACGAAAGCGT


GGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAGTACTA


GGTGTCGGGGGTTACCCCCCTCGGTGCCGCAGCTAACGCATTAAGTACTCCGCCT


GGGAAGTACGCTCGCAAGAGTGAAACTCAAAGGAATTGACGGGGACCCGCACAAG


TAGCGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCTAAGCTTGAC


ATCCCACTGACCTCTCCCTAATCGGAGATTTCCCTTCGGGGACAGTGGTGACAGGT


GGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGA


GCGCAACCCTTGCCTTTAGTTGCCAGCATTAAGTTGGGCACTCTAGAGGGACTGCC


GAGGATAACTCGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGCTT


AGGGCTACACACGTGCTACAATGGGTGGTACAGAGGGTTGCCAAGCCGCGAGGTG


GAGCTAATCCCTTAAAGCCATTCTCAGTTCGGATTGTAGGCTGAAACTCGCCTACAT


GAAGCTGGAGTTACTAGTAATCGCAGATCAGAATGCTGCGGTGAATGCGTTCCCGG


GTCTTGTACACACCGCCCGTCACACCATGGAAGTTGGGGGCGCCCGAAGCCGGTT


AGCTAACCTTTTAGGAAGCGGCCGTCGAAGGTGAAACCAATGACTGGGGTGAAGTC


GTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCT





SEQ ID NO: 83 Escherichia fergusonii / Escherichia coli


TTGAAGAGTTTGATCATGGCTCAGATTGAACGCTGGCGGCAGGCCTAACACATGCA


AGTCGAACGGTAACAGGAAGCAGCTTGCTGCTTTGCTGACGAGTGGCGGACGGGT


GAGTAATGTCTGGGAAACTGCCTGATGGAGGGGGATAACTACTGGAAACGGTAGCT


AATACCGCATAACGTCGCAAGACCAAAGAGGGGGACCTTCGGGCCTCTTGCCATCG


GATGTGCCCAGATGGGATTAGCTAGTAGGTGGGGTAACGGCTCACCTAGGCGACG


ATCCCTAGCTGGTCTGAGAGGATGACCAGCCACACTGGAACTGAGACACGGTCCAG


ACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGATGC


AGCCATGCCGCGTGTATGAAGAAGGCCTTCGGGTTGTAAAGTACTTTCAGCGGGGA


GGAAGGGAGTAAAGTTAATACCTTTGCTCATTGACGTTACCCGCAGAAGAAGCACC


GGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGGTGCAAGCGTTAATCGGA


ATTACTGGGCGTAAAGCGCACGCAGGCGGTTTGTTAAGTCAGATGTGAAATCCCCG


GGCTCAACCTGGGAACTGCATCTGATACTGGCAAGCTTGAGTCTCGTAGAGGGGG


GTAGAATTCCAGGTGTAGCGGTGAAATGCGTAGAGATCTGGAGGAATACCGGTGGC


GAAGGCGGCCCCCTGGACGAAGACTGACGCTCAGGTGCGAAAGCGTGGGGAGCAA


ACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGTCGACTTGGAGGTTGT


GCCCTTGAGGCGTGGCTTCCGGAGCTAACGCGTTAAGTCGACCGCCTGGGGAGTA


CGGCCGCAAGGTTAAAACTCAAATGAATTGACGGGGGCCCGCACAAGCGGTGGAG


CATGTGGTTTAATTCGATGCAACGCGAAGAACCTTACCTGGTCTTGACATCCACGGA


AGTTTTCAGAGATGAGAATGTGCCTTCGGGAACCGTGAGACAGGTGCTGCATGGCT


GTCGTCAGCTCGTGTTGTGAAATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTT


ATCCTTTGTTGCCAGCGGTCCGGCCGGGAACTCAAAGGAGACTGCCAGTGATAAAC


TGGAGGAAGGTGGGGATGACGTCAAGTCATCATGGCCCTTACGACCAGGGCTACA


CACGTGCTACAATGGCGCATACAAAGAGAAGCGACCTCGCGAGAGCAAGCGGACC


TCATAAAGTGCGTCGTAGTCCGGATTGGAGTCTGCAACTCGACTCCATGAAGTCGG


AATCGCTAGTAATCGTGGATCAGAATGCCACGGTGAATACGTTCCCGGGCCTTGTA


CACACCGCCCGTCACACCATGGGAGTGGGTTGCAAAAGAAGTAGGTAGCTTAACCT


TCGGGAGGGCGCTTACCACTTTGTGATTCATGACTGGGGTGAAGTCGTAACAAGGT


AACCGTAGGGGAACCTGCGGTTGGATCACCTCCTT









The invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having,” “containing,” “involving,” and variations thereof herein, is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.


Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms hall include the singular. The methods and techniques of the present disclosure are generally performed according to conventional methods well-known in the art. Generally, nomenclatures used in connection with, and techniques of biochemistry, enzymology, molecular and cellular biology, microbiology, virology, cell or tissue culture, genetics and protein and nucleic chemistry described herein are those well-known and commonly used in the art. The methods and techniques of the present disclosure are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated.


The present invention is further illustrated by the following Examples, which in no way should be construed as further limiting. The entire contents of all of the references (including literature references, issued patents, published patent applications, and co-pending patent applications) cited throughout this application are hereby expressly incorporated by reference, in particular for the teaching that is referenced hereinabove. However, the citation of any reference is not intended to be an admission that the reference is prior art.


EXAMPLES
Example 1: Efficacy of Bacterial Compositions to Decolonize ESBL

As shown in FIG. 1, mice were treated with antibiotics (e.g., 0.5 g/L ampicillin) for 7 days prior to challenge with CRE or ESBL-producing Enterobacteriaceae challenge (Escherichia coli ATCC BAA-2777, “ESBL”). On day-3, mice were challenged with CRE or ESBL. On days 0.1, and 2, mice were administered treatment (e.g., PBS (control), a 36-mix live biotherapeutic product (36-mix), or stool fraction library from a human donor (Donor 1 SFL)). Fecal samples (pellets) were collected at various time points post-treatment to quantify colony forming units (CFU) as measure of ESBL colonization levels. The efficacy of a treatment in reducing CRE or ESBL colonization was assessed.


As shown in FIG. 2, the 36-mix and SFL derived from Donor 1 were capable of reducing ESBL colonization levels, however the SFL derived from Donor 1 reduce ESBL colonization to lower levels. Several of the mice treated with the 35-mix exhibited a greater reduction in ESBL colonization. Stools from the mice treated with the 36-mix and having the lowest levels of ESBL colonization were subjected to metagenomic sequencing, which identified several mouse-derived taxa that were present in these mice compared to mice that received the 36-mix and higher levels of ESBL colonization.


Additional bacterial strains were evaluated for combination with strains of the 36-mix. A bacterial mixture comprising the strains present in the 36-mix and 11 additional strains, for a total of 47 bacterial strains (47-mix), was prepared. See, FIG. 3 and Table 1.


Example 2: Efficacy of Bacterial Compositions Comprising 47 Bacterial Strains to Decolonize CRE and ESBL

Mice were treated with antibiotics (e.g., 0.5 g/L ampicillin) for 7 days prior to challenge with carbapenem-resistant Klebsiella pneumoniae challenge (Klebsiella pneuomoniae ATCC BAA-2814, “CRE”) or ESBL-producing Enterobacteriaceae challenge (Escherichia coli ATCC BAA-2777, “ESBL”) (FIG. 1). On day-3, mice were challenged with CRE or ESBL. On days 0, 1, and 2, mice were administered treatment (e.g., PBS (control), or the 47-mix live biotherapeutic product (47-mix). Fecal samples (pellets) were collected at various time points post-treatment to quantify colony forming units (CFU) as measure of CRE or ESBL colonization levels.


Colonization levels of CRE and ESBL in mice are shown in FIG. 4. Administration of the 47-mix bacterial composition resulted in a reduction of both CRE and ESBL by at least 3-logs as compared to mice that received the control (PBS).


Example 3: Efficacy of Bacterial Compositions Comprising 47 Bacterial Strains to Decolonize ESBL or CRE

Mice were treated with antibiotics (e.g., 0.5 g/L ampicillin) for 7 days prior to challenge with carbapenem-resistant Klebsiella pneumoniae challenge (Klebsiella pneuomoniae ATCC BAA-2814, “CRE”) or ESBL-producing Enterobacteriaceae challenge (Escherichia coli ATCC BAA-2777, “ESBL”) (FIG. 1). On day-3, mice were challenged with CRE or ESBL. On days 0, 1, and 2, mice were administered treatment (e.g., PBS (control), the 47-mix live biotherapeutic product (47-mix), stool fraction library derived by culturing stool from a second human donor (Donor 2 SFL), or a bacterial mixture obtained by introducing fecal matter from a first human donor (Donor 1) into a mouse and obtaining stool from the mouse to prepare a fecal matter transplant (Donor 1-inoculated mouse FMT).


Fecal samples (pellets) were collected at various time points post-treatment to quantify colony forming units (CFU) as measure of CRE or ESBL colonization levels. Colonization levels of ESBL and CRE in mice are shown in FIGS. 5A and 5B, respectively.


Administration of the 47-mix bacterial composition resulted in a reduction in both ESBL and CRE colonization by at least 2-logs by day 7. Colonization of both ESBL and CRE were further reduced at both 10 days and 14 days post treatment.


Example 4: Efficacy of Bacterial Compositions Comprising Bacterial Strains and Taurine to Decolonize ESBL or CRE

Mice are treated with antibiotics (e.g., 0.5 g/L ampicillin) for 7 days prior to challenge with carbapenem-resistant Klebsiella pneumoniae challenge (Klebsiella pneuomoniae ATCC BAA-2814, “CRE”) or ESBL-producing Enterobacteriaceae challenge (Escherichia coli ATCC BAA-2777, “ESBL”). On day-3, mice are challenged with CRE or ESBL. Mice are administered the following treatment conditions:

    • PBS (control),
    • PBS+taurine (taurine only),
    • live biotherapeutic product (any of the compositions described herein), and
    • live biotherapeutic product+taurine (any of the compositions described herein+taurine).


Taurine may be administered in the same composition with the live biotherapeutic product or in a separate composition, which may be administered prior to, at the same time, or after administration of the live biotherapeutic product.


Fecal samples (pellets) are collected at various time points post-treatment to quantify colony forming units (CFU) as measure of CRE or ESBL colonization levels.

Claims
  • 1. A composition comprising two or more purified bacterial strains of species selected from the group consisting of a purified bacterial strain of Collinsella aerofaciens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bacteroides caccae, Bacteroides xylanisolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides_B vulgatus, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides faecis, Bacteroides ovatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Paraclostridium massiliensis, Paeniclostridium sordellii, Absiella innocuum, Absiella innocuum, Erysipelatoclostridium ramosum, Clostridium_M citroniae, Clostridium_M clostridioforme, Eubacterium_E hallii, Agathobacter rectale, Blautia producta, Blautia_A obeum, Dorea longicatena, Coprococcus_B comes, Anaerostipes caccae, Agathobaculum sp, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium_A sp, Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.
  • 2. A composition comprising two or more purified bacterial strains, wherein the two or more purified bacterial strains comprise 16S rDNA sequences having at least 97% sequence identity with nucleic acid sequences selected from the group consisting of SEQ ID NOs: 1-47.
  • 3. The composition of claim 1 or 2, wherein the composition comprises 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, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, or at least 47 purified bacterial strains.
  • 4. A composition comprising purified bacterial strains of species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae.
  • 5. A composition comprising purified bacterial strains comprising 16S rDNA sequences having at least 97% sequence identity to nucleic acid sequences of SEQ ID NOs: 10, 29, 30, and 36.
  • 6. The composition of any one of claims 1-5, wherein the composition comprises bacterial strains that originate from more than one human donor.
  • 7. The composition of any one of claims 1-6, further comprising taurine.
  • 8. A composition comprising (1) one or more purified bacterial strains belonging to the phylum Firmicutes or Bacteroidetes;(2) one or more purified bacterial strains selected from the group consisting of an Escherichia species and a Fusobacterium species; and(3) taurine.
  • 9. A composition comprising (1) one or more purified bacterial strains belonging to the phylum Firmicutes;(2) one or more purified bacterial strains of Escherichia species; and(3) taurine.
  • 10. A composition comprising (1) one or more purified bacterial strains belonging to the phylum Firmicutes;(2) one or more purified bacterial strains of Fusobacterium species; and(3) taurine.
  • 11. A composition comprising (1) one or more purified bacterial strains belonging to the phylum Bacteroidetes;(2) one or more purified bacterial strains of Escherichia species and(3) taurine.
  • 12. A composition comprising (1) one or more purified bacterial strains belonging to the phylum Bacteroidetes;(2) one or more purified bacterial strains of Fusobacterium species; and(3) taurine.
  • 13. A composition comprising a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species, and one or more purified bacterial strains of species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.
  • 14. A composition comprising a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species, and one or more purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, and Phascolarctobacterium faecium; and taurine.
  • 15. A composition comprising a purified bacterial strain belonging to Escherichia species and one or more purified bacterial strains of species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.
  • 16. A composition comprising purified bacterial strain belonging to Fusobacterium species and one or more purified bacterial strains of species selected from the group consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium bifermentans, Clostridium sordelli, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, and Phascolarctobacterium faecis; and taurine.
  • 17. A composition comprising a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species, and one or more purified bacterial strains of species selected from the group consisting of Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.
  • 18. A composition comprising a purified bacterial strain belonging to Escherichia species and one or more purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.
  • 19. A composition comprising a purified bacterial strain belonging to Fusobacterium species and one or more purified bacterial strains of species selected from the group consisting of Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides fragilis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, and Alistipes shahii; and taurine.
  • 20. A composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 21. A composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species; and taurine.
  • 22. A composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 23. A composition comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 24. A composition comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species; and taurine.
  • 25. A composition comprising Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Dorea longicatena, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 26. A composition comprising Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613), cf. Clostridium sp. MLG055 (Erysipelotrichaceae bacterium 2_2_44A), Clostridium indolis (Anaerostipes caccae DSM 14662), Anaerotruncus colihominis (Anaerotruncus colihominis DSM 17241), Ruminococcus sp. ID8 (Lachnospiraceae bacterium 2_1_46FAA), Clostridium lavalense (Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp. D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp. 316002/08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 27. A composition comprising Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613), cf. Clostridium sp. MLG055 (Erysipelotrichaceae bacterium 2_2_44A), Clostridium indolis (Anaerostipes caccae DSM 14662), Anaerotruncus colihominis (Anaerotruncus colihominis DSM 17241), Ruminococcus sp. ID8 (Lachnospiraceae bacterium 2_1_46FAA), Clostridium lavalense (Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp. D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp. 316002/08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), a purified bacterial strain belonging to Escherichia species; and taurine.
  • 28. A composition comprising Clostridium saccharogumia (Clostridium ramosum JCM 1298), Flavonifractor plautii (Pseudoflavonifractor capillosus ATCC 29799), Clostridium hathewayi (Clostridium saccharolyticum WM1), Blautia coccoides (Lachnospiraceae bacterium 6_1_63FAA), Clostridium spp. (Clostridium bolteae ATCC BAA-613), cf. Clostridium sp. MLG055 (Erysipelotrichaceae bacterium 2_2_44A), Clostridium indolis (Anaerostipes caccae DSM 14662), Anaerotruncus colihominis (Anaerotruncus colihominis DSM 17241), Ruminococcus sp. ID8 (Lachnospiraceae bacterium 2_1_46FAA), Clostridium lavalense (Clostridium asparagiforme DSM 15981), Clostridium symbiosum (Clostridium symbiosum WAL-14163), Clostridium ramosum, Eubacterium contortum (Clostridium sp. D5), Clostridium scindens (Lachnospiraceae bacterium 5_1_57FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), Clostridium sp. 316002/08 (Clostriales bacterium 1_7_47FAA), Lachnospiraceae bacterium A4 (Lachnospiraceae bacterium 3_1_57FAA_CT1), a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 29. A composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 30. A composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Escherichia species; and taurine.
  • 31. A composition comprising Clostridium bolteae, Anaerotruncus colihominis, Sellimonas intestinalis, Clostridium symbiosum, Blautia producta, Erysipelotrichaceae bacterium, Flavinofractor plautii, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 32. A composition comprising Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Alistipes putredinis, Alistipes shahii, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecis, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 33. A composition comprising Collinsella aerofaciens, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides cellulosilyticus, Bacteroides uniformis, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Alistipes shahii, Bifidobacterium adolescentis, Bifidobacterium longum, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium rectale, Anaerostipes caccae, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecis, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 34. A composition comprising Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides xyalinosolvens, Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides faecis, Bacteroides uniformis, Bacteroides vulgatus, Alistipes putredinis, Alistipes shahii, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Eubacterium hallii, Eubacterium rectale, Blautia obeum, Blautia producta, Coprococcus comes, Dorea longicatena, a purified bacterial strain belonging to Escherichia species, a purified bacterial strain belonging to Fusobacterium species; and taurine.
  • 35. A composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.
  • 36. A composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Clostridium clostridioforme, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.
  • 37. A composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Clostridium clostridioforme, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Clostridium innocuum, Dorea longicatena, Collinsella aerofaciens, Eubacterium hallii, Bacteroides faecis, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.
  • 38. A composition comprising Blautia producta, Bifidobacterium longum, Bifidobacterium adolescentis, Paeniclostridium sordellii, Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, Escherichia coli, Paraclostridium bifermentans, Clostridium citroniae, Anaerostipes caccae, Fusobacterium mortiferum, Blautia obeum, Clostridium innocuum, Agathobaculum butyriciproducens, Odoribacter sp., Bacteroides fragilis, Bacteroides ovatus, Clostridium bolteae, Anaerotruncus colihominis, Drancourtella massiliensis, Clostridium symbiosum, Blautia producta, Dorea longicatena, Erysipelotrichaceae bacterium, Flavonifractor plautii; and taurine.
  • 39. A composition comprising Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.
  • 40. A composition comprising Bacteroides caccae, Bacteroides cellulosilyticus, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Clostridium citroniae, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Escherichia coli; and taurine.
  • 41. A composition comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Eubacterium rectale, Odoribacter splanchnicus, Parabacteroides distasonis, Parabacteroides merdae, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.
  • 42. A composition comprising Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Coprococcus comes, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Parabacteroides distasonis, Bacteroides xylanisolvens, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Alistipes shahii, Anaerostipes caccae, Phascolarctobacterium faecium, Fusobacterium mortiferum, Escherichia coli; and taurine.
  • 43. A composition comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Clostridium innocuum, Paeniclostridium sordellii, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Blautia obeum, Alistipes putredinis, Collinsella aerofaciens, Eubacterium hallii, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Bacteroides fragilis, Fusobacterium mortiferum, Paraclostridium bifermentans, Escherichia coli; and taurine.
  • 44. A composition comprising Bacteroides faecis, Bacteroides ovatus, Bacteroides vulgatus, Bifidobacterium longum, Blautia producta, Clostridium citroniae, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Phascolarctobacterium faecium, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.
  • 45. A composition comprising bacterial strains of species Bacteroides vulgatus, Clostridium citroniae, and Phascolarctobacterium faecium, and one or more purified bacterial strains of species selected from the group consisting of Bacteroides faecis, Bacteroides ovatus, Bifidobacterium longum, Blautia producta, Clostridium clostridioforme, Clostridium innocuum, Dorea longicatena, Erysipelatoclostridium ramosum, Odoribacter splanchnicus, Alistipes putredinis, Collinsella aerofaciens, Blautia obeum, Anaerostipes caccae, Agathobaculum butyriciproducens, Fusobacterium mortiferum, Escherichia coli; and taurine.
  • 46. A composition comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides faecis, Bacteroides vulgatus, Odoribacter splanchnicus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Dorea longicatena, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.
  • 47. A composition comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Parabacteroides distasonis, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Anaerostipes caccae, Blautia obeum, Blautia producta, Agathobaculum butyriciproducens, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.
  • 48. A composition comprising Collinsella aerofaciens, Bifidobacterium longum, Bacteroides ovatus, Bacteroides vulgatus, Alistipes putredinis, Clostridium citroniae, Clostridium clostridioforme, Erysipelatoclostridium ramosum, Erysipelotrichaceae bacterium 6_1_45, Blautia obeum, Blautia producta, Dorea longicatena, Phascolarctobacterium faecium, Escherichia coli, Fusobacterium mortiferum; and taurine.
  • 49. A composition comprising purified bacterial strains of species Bacteroides faecis, Bacteroides vulgatus, Phascolartcobacterium faecium, and Clostridium citroniae; and taurine.
  • 50. The composition of any one of claims 8-49, further comprising one or more bacterial strain selected from the group consisting of Barnesiella intestinihominis, Blautia luti, Blautia faecis, Blautia wexlerae, Ruminococcus faecis, Clostridium bolteae, Butyricimonas synergistica, Bilophila wadsworthia, Akkermansia muciniphila, Parasuterella excrementinihominis, and Prevotella copri.
  • 51. The composition of any one of claims 8-50, wherein the composition comprises between about 40 mg to about 3000 mg taurine.
  • 52. The composition of claim 51, wherein the composition comprises between about 100 mg to about 2000 mg taurine.
  • 53. The composition of claim 51, wherein the composition comprises between about 500 mg to about 1500 mg taurine.
  • 54. The composition of any one of claims 1-53, wherein the composition is effective in suppressing the replication, survival, and/or colonization of one or more pathogenic organisms.
  • 55. The composition of any one of claims 1-54, wherein the composition is effective in treating an infection by a pathogenic organism in a subject.
  • 56. The composition of claim 54 or 55, wherein the pathogenic organism is susceptible to antibiotics.
  • 57. The composition of claim 54 or 55, wherein the pathogenic organism is resistant to one or more antibiotics.
  • 58. The composition of any one of claim 54, 55, or 57, wherein the pathogenic organism is a multi-drug resistant organism.
  • 59. The composition of claim 58, wherein the multi-drug resistant organism is Carbapenem Resistant Enterobacteriaceae (CRE) or Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.
  • 60. The composition of claim 59, wherein the Carbapenem Resistant Enterobacteriaceae (CRE) is carbapenem-resistant Klebsiella pneumoniae.
  • 61. The composition of claim 60, wherein the carbapenem-resistant Klebsiella pneumoniae is carbapenem-resistant Klebsiella pneumoniae ATCC 700721.
  • 62. The composition of claim 59, wherein the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae or EBSL-producing E. coli.
  • 63. The composition of claim 62, wherein the ESBL-producing Enterobacteriaceae is ESBL-producing K. pneumoniae subsp. pneumoniae (ATCC 700721), ESBL-producing E. coli ATCC BAA 2777, adherent/invasive E. coli (AIEC), Shiga toxin-producing E. coli (STEC), Verocytotoxin-producing E. coli (VTEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), or diffusely adherent E. coli (DAEC).
  • 64. The composition of any one of claims 1-63, wherein the bacterial strains are lyophilized.
  • 65. The composition of any one of claims 1-63, wherein the bacterial strains are spray-dried.
  • 66. The composition of any one of claims 1-65, wherein one or more of the bacterial strains are in spore form.
  • 67. The composition of any one of claims 1-66, wherein each of the bacterial strains is in spore form.
  • 68. The composition of any one of claims 1-66, wherein one or more of the bacterial strains are in vegetative form.
  • 69. The composition of any one of claim 1-65 or 68, wherein each of the bacterial strains is in vegetative form.
  • 70. The composition of any one of claims 1-69, wherein the composition further comprises one or more enteric polymers.
  • 71. A pharmaceutical composition comprising the composition of any one of claims 1-70, further comprising a pharmaceutically acceptable excipient.
  • 72. The pharmaceutical composition of claim 71, wherein the pharmaceutical composition is formulated for oral delivery.
  • 73. The pharmaceutical composition of claim 71 or 72, wherein the pharmaceutical composition is formulated for rectal delivery.
  • 74. The pharmaceutical composition of any one of claims 71-73, wherein the pharmaceutical composition is formulated for delivery to the intestine.
  • 75. The pharmaceutical composition of any one of claims 71-74, wherein the pharmaceutical composition is formulated for delivery to the colon.
  • 76. The pharmaceutical composition of any one of claims 71-75, wherein the pharmaceutical composition is administered as one dose.
  • 77. The pharmaceutical composition of any one of claims 71-75, wherein the pharmaceutical composition is administered as multiple doses.
  • 78. The pharmaceutical composition of claim 76 or 77, wherein each dose comprises the administration of multiple capsules.
  • 79. A food product comprising the composition of any one of claims 1-78 and a nutrient.
  • 80. A method of suppressing infection by a pathogenic organism in a subject, comprising administering to the subject a therapeutically effective amount of the composition of any one of claims 1-78 or the food product of claim 79.
  • 81. A method of reducing or preventing colonization by a pathogenic organism in a subject, comprising administering to the subject a therapeutically effective amount of the composition of any one of claims 1-78 or the food product of claim 79.
  • 82. A method of treating infection by a pathogenic organism in a subject, comprising administering to the subject a therapeutically effective amount of the composition of any one of claims 1-78 or the food product of claim 79.
  • 83. The method of any one of claims 80-82, wherein the pathogenic organism is a multi-drug resistant organism.
  • 84. The method of claim 80-83, wherein the pathogenic organism is Klebsiella pneumoniae.
  • 85. The method of claim 84, wherein the Klebsiella pneumoniae is multi-drug resistant.
  • 86. The method of claim 85, wherein the multi-drug resistant Klebsiella pneumoniae is carbapenem-resistant Klebsiella pneumoniae.
  • 87. The method of claim 80-86, wherein the pathogenic organism is Extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae.
  • 88. The method of claim 87, wherein the ESBL producing Enterobacteriaceae is Escherichia coli (E. coli).
  • 89. The method of claim 88, wherein the E. coli is adherent/invasive E. coli (AIEC), Shiga toxin-producing E. coli (STEC), Verocytotoxin-producing E. coli (VTEC), enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), or diffusely adherent E. coli (DAEC).
  • 90. The method of any one of claims 80-89, wherein the subject is human.
  • 91. The method of any one of claims 80-90, wherein the composition is administered to the subject more than once.
  • 92. The method of any one of claims 80-91, wherein the composition is administered to the subject by oral administration.
  • 93. The method of any one of claims 80-91, wherein the composition is administered to the subject by rectal administration.
  • 94. The method of any one of claims 80-93, wherein the administering suppresses the replication, survival, and/or colonization of the pathogenic organism.
  • 95. The method of any one of claims 80-94, wherein the administration of the composition is not preceded by administration of vancomycin.
  • 96. The method of any one of claims 80-94, further comprising administering an antibiotic to the subject prior to administration of the composition.
  • 97. The method of claim 96, wherein the antibiotic is vancomycin.
  • 98. The method of any one of claims 80-97, further comprising administering a composition comprising taurine to the subject.
  • 99. The method of claim 98, wherein the composition comprising taurine is administered to the subject prior to and/or after administration of the composition of any one of claims 1-78 or the food product of claim 79.
  • 100. The method of any one of claims 80-97, wherein the subject has been administered a composition comprising taurine prior to the administration of the composition of any one of claims 1-78 or the food product of claim 79.
  • 101. The method of any one of claims 98-100, wherein the subject is administered between about 40 mg to about 3000 mg taurine per day.
  • 102. The method of any one of claims 98-101, wherein the subject receives between about 100 mg to about 2000 mg taurine per day.
  • 103. The method of any one of claims 98-102, wherein the subject receives between about 500 mg to about 1500 mg taurine per day.
RELATED APPLICATION

This application claims the benefit under 35 U.S.C. § 119(e) of U.S. provisional application No. 63/151,003 filed Feb. 18, 2021, the entire contents of which are incorporated by reference herein.

PCT Information
Filing Document Filing Date Country Kind
PCT/US2022/017043 2/18/2022 WO
Provisional Applications (1)
Number Date Country
63151003 Feb 2021 US