LONG CHAIN DICARBOXYLIC FATTY ACID (LCDFA) PRODUCING MICROBES AND USES THEREOF

Description

FIELD OF INVENTION

The present invention relates to the treatment of gastrointestinal inflammation and gastric tract acid (GTA) long-chain fatty acid deficiency through the manipulation of the gut microbiome. The invention also relates to compositions and methods of increasing gastric tract acid (GTA) production in a mammalian subject.

BACKGROUND OF THE INVENTION

Chronic inflammation is widely accepted as the primary underlying cause of gastrointestinal (GI) cancers, including colorectal cancer, pancreatic cancer, gastric cancer, esophageal cancer, ovarian cancer, and others (Marusawa and Jenkins 2014, Hussain and Harris 2007, Chapkin, McMurray and Lupton 2007, Demaria et al. 2010, Itzkowitz and Yio 2004, Maccio and Madeddu 2012, Schwartsburd 2004, Terzic et al. 2010, Wu et al. 2014). Chronic inflammation can lead to oxidative stress, which can subsequently result in carcinogenic events and genetic mutations that drive the malignant transformation of cells. (Mannick et al and Zhang et al). Cancer growth is subsequently driven by the proinflammatory milieu of cytokines and angiogenic factors in the microenvironment.

Despite the preponderance of evidence linking GI cancers to chronic inflammation, all of the emphasis on the early detection of cancer (take for example colorectal cancer), has focused exclusively on the improved detection of tumor-derived markers or precancerous lesions, and not underlying metabolic or inflammatory risk factors. In the case of colorectal cancer, the primary screening modalities are either direct visualization of cancer growth or precancerous lesions by endoscopy, the detection of occult blood in the stool, or more recently methylated tumor DNA in either feces or blood. For each of these modalities to be effective, there has to be a minimal tumor burden present that is of sufficient magnitude to either physically view or biopsy a lesion, or sufficient tumor load to produce detectable levels of tumor-derived biomarkers in either the feces or blood. Therefore, such approaches offer no hope for preventing the occurrence of the disease to begin with; but rather only offer hope in the form of early-stage detection where treatment is generally more effective.

A key component of the inflammatory status of the gut was identified by Ritchie et al. through a non-targeted metabolomic analysis of small molecules that differentiated colorectal cancer, pancreatic cancer, and ovarian cancer from disease-free subjects (Ritchie et al. 2010a, Ritchie et al. 2010c, Ritchie et al. 2010b, Ritchie et al. 2011, Ritchie et al. 2013b, Ritchie et al. 2013a, Ritchie et al. 2015). A novel family of metabolites initially proposed to be vitamin E metabolites, but subsequently shown to be novel long-chain polyunsaturated dicarboxylic fatty acids (called GTAs for gastric tract acids), ranging between 28 and 36 carbons in size, and with molecular weights between approximately 446 and 596 Da, were shown to be consistently reduced in the serum of subjects with these cancers compared to controls.

GTAs were shown to possess anti-inflammatory as well as anti-proliferative activity in vitro (Ritchie et al. 2011) though the co-administration of semi-purified GTA-containing and GTA-deficient extracts with LPS in various cell systems. The anti-inflammatory activity was shown to be mediated through NF-κB, a transcription factor involved in the activation of several pro-inflammatory cytokines, including TNF-alpha and Interleukin-1β. Specifically, GTAs significantly upregulated IκBα, an inhibitory protein that inactivates NF-κB. NF-κB overexpression has been linked to multiple aspects of chronic inflammation, and has been the target of therapeutic downregulation by synthetic and natural products (Ben-Neriah and Karin 2011, Spehlmann and Eckmann 2009, Surh et al. 2001, Xu et al. 2005, Freitas and Fraga 2018).

These GTAs continue to be a source of interest and research to better understand their mechanism of action and potential role in treating inflammation and disease, such as cancer.

SUMMARY OF THE INVENTION

It is an object of the invention to provide new methods for detecting and reducing gastrointestinal (GI) inflammation in a subject.

An approach is thus provided herein for identifying subjects with GI inflammation by measuring levels of long-chain dicarboxylic fatty acids (LCDFAs), or GTAs, in the blood, followed by treatment with chemical agents or micro-organisms to restore or augment these GTA levels.

In certain embodiments, the micro-organisms are long-chain fatty acid-producing bacteria, especially those from the genus Blautia and species Faecalibacterium prausnitzii.

Particular microbial species are also shown to be associated with these GTA levels, and thus strategies are provided to augment these microbial species for the purpose of reducing GI inflammation.

Also provided is an approach for identifying an underlying metabolic inflammatory condition associated with the development of various GI-related cancers, including but not limited to colorectal cancer, pancreatic cancer, and ovarian cancer, followed by an approach to reduce risk through therapeutic treatment of the underlying inflammation.

Accordingly, there is provided a method for increasing gastric tract acid (GTA) production in a mammalian subject. The method comprises administering a therapeutically-effective amount of a composition comprising at least one live or attenuated culture of a microbial species selected from the genus Blautia, species Faecalibacterium prausnitzii, genus Bacteroides, family Ruminococcaceae, family Lachnospiraceae, genus Coprococcus, genus Roseburia, genus Oscillospira, species Ruminococcus bromii, genus Ruminococcus, family Costridiaceae, species Dorea formicigenerans, species Bacteroides uniformis, genus Dorea, genus Streptococcus, order Clostridiales, genus Anaerostipes, genus Dialister, species Bifidobacterium adolescentis, family Coriobacteriaceae, genus Faecalibacterium, genus Sutterella, species Bacteroides ovatus, genus Parabacteroides, genus Ruminococcus, species Bacteroides faecis, species Eubacterium biforme, genus Phascolartobacterium, and family Enterobacteriaceae; or a prebiotic composition which increases growth and/or viability of said microbial species in the gut; wherein the composition increases the synthesis of at least one GTA dicarboxylic fatty acid metabolite in said subject.

In certain embodiments, the method further comprises a step of measuring circulating levels of one or more GTA dicarboxylic fatty acid metabolite in the subject. The composition may thus be administered if the levels of the one or more GTA dicarboxylic fatty acid metabolite are found to be lower in the subject than a predetermined control level, an earlier test value obtained for the subject, or a normal level for healthy subjects. For example, yet without wishing to be limiting, the control may include a predetermined threshold value for the at least one GTA dicarboxylic fatty acid metabolite that is typical of a healthy individual.

In further embodiments, the composition may comprise a live or attenuated culture of a microbial species from the genus Blautia, a live or attenuated culture of Faecalibacterium prausnitzii, or a combination thereof. Typically such cultures will be formulated within a pharmaceutically-acceptable excipient or carrier suitable for administration to the gastrointestinal tract of a subject.

In yet further embodiments, the GTA dicarboxylic fatty acid metabolite is a dicarboxylic fatty acid between 28 and 36 carbons comprised of a dimeric fatty acid structure of two shorter chains ranging between 14 and 18 carbons in length joined by a single or double bond. In further embodiments, the GTA dicarboxylic fatty acid metabolite may be one of the following: GTA-446, GTA-448, GTA-450, GTA-452, GTA-464, GTA-466, GTA-468, GTA-474, GTA-476, GTA-478, GTA-484, GTA-490, GTA-492, GTA-494, GTA-502, GTA-504, GTA-512, GTA-518, GTA-520, GTA-522, GTA-524, GTA-530, GTA-532, GTA-536, GTA-538, GTA-540, GTA-550, GTA-574, GTA-576, GTA-580, GTA-590, GTA-592, GTA-594, and GTA-596.

In non-limiting embodiments, the GTA dicarboxylic fatty acid metabolite may have an accurate neutral mass within 1 PPM Dalton mass accuracy of 446.3396 (GTA-446), 448.3553 (GTA-448), 450.3709 (GTA-450), 452.3866 (GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), 468.3814 (GTA-468), 474.3736 (GTA-474), 476.3866 GTA-476, 478.4022 (GTA-478), 484.3764 (GTA-484), 490.3658 (GTA-490), 492.3815 (GTA-492), 494.3971 (GTA-494), 502.4022 (GTA-502), 504.4195 (GTA-504), 512.4077 (GTA-512), 518.3974 (GTA-518), 520.4128 (GTA-520), 522.4284 (GTA-522), 524.4441 (GTA-524), 530.4335 (GTA-530), 532.4492 (GTA-532), 536.4077 (GTA-536), 538.4233 (GTA-538), 540.4389 (GTA-540), 550.4597 (GTA-550), 574.4597 (GTA-574), 576.4754 (GTA-576), 580.5067 (GTA-580), 590.4546 (GTA-590), 592.4703 (GTA-592), 594.4859 (GTA-594), or 596.5016 (GTA-596).

In further non-limiting embodiments, the GTA dicarboxylic fatty acid metabolite may have a molecular formula of C₂₈H₄₆O₄(GTA-446), C₂₈H₄₈O₄(GTA-448), C₂₈H₅₀O₄(GTA-450), C₂₈H₅₂O₄(GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), C₂₈H₅₂O₅(GTA-468), C₃₀H₅₀O₄(GTA-474), C₃₀H₅₂O₄GTA-476, C₃₄H₅₄O₄(GTA-478), C₂₈₅₂O₆(GTA-484), C₃₀H₅₀O₅(GTA-490), C₃₀H₅₂O₅(GTA-492), C₃₄H₅₄O₅(GTA-494), C₃₂H₅₄O₄(GTA-502), C₃₂H₅₆O₄(GTA-504), C₃₀H₅₆O₆(GTA-512), C₃₂H₅₄O₅(GTA-518), C₃₂H₅₆O₅(GTA-520), C₃₂H₅₈O₅(GTA-522), C₃₂H₆₀O₅GTA-524, C₃₄H₅₈O₄(GTA-530), C₃₄H₆₀O₄(GTA-532), C₃₂H₅₆O₆(GTA-536), C₃₂H₅₈O₆(GTA-538), C₃₂H₆₀O₆(GTA-540), C₃₄H₆₂O₅(GTA-550), C₃₆H₆₂O₅(GTA-574), C₃₆H₆₄O₅(GTA-576), C₃₆H₆₈O₅(GTA-580), C₃₆H₆₂O₆(GTA-590), C₃₆H₆₄O₆(GTA-592), C₃₆H₆₆O₆(GTA-594), or C₃₆H₆₈O₆(GTA-596).

In further non-limiting embodiments, the GTA dicarboxylic fatty acid metabolite may be measured using collision induced dissociation (CID) tandem mass spectrometry. The GTAs may be one or more of the GTA dicarboxylic fatty acid metabolites listed below:

GTA-446, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 446.3396, the molecular formula of C₂₈H₄₆O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 445: 427, 409, 401, and 383,

GTA-448, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 448.3553, the molecular formula of C₂₈H₄₈O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 447: 429, 411, 403, and 385,

GTA-450, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 450.3709, the molecular formula of C₂₈H₅₀O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 449: 431, 413, 405, and 387,

GTA-452, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 452.3866, the molecular formula of C₂₈H₅₂O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 451: 433, 407, and 389,

GTA-464, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 464.3522, the molecular formula of C₂₈H₄₈O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 463: 445, 419, 401, and 383,

GTA-466, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 466.3661, the molecular formula of C₂₈H₅₀O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 465: 447, 421, and 403,

GTA-468, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 468.3814, having the molecular formula of C₂₈H₅₂O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 467: 449, 423, and 405,

GTA-474, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 474.3736, having the molecular formula of C₃₀H₅₀O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 473: 455, 429, and 411,

GTA-476, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 476.3866, having the molecular formula of C₃₀H₅₂O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 475: 457, 431, 439 and 413,

GTA-478, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 478.4022, having the molecular formula of C₃₀H₅₄O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 477: 459, 433, 441 and 415,

GTA-484, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 484.3764, having the molecular formula of C₂₈H₅₂O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 483: 465, 315, 439 483, 421, and 447,

GTA-490, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 490.3658, having the molecular formula of C₃₀H₅₀O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 489: 445, 471, 427 and 319,

GTA-492, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 492.3815, having the molecular formula of C₃₀H₅₂O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 491: 241, 249, 267, 473, and 447,

GTA-494, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 494.3971, having the molecular formula of C₃₀H₅₄O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 493: 475, 215, and 449,

GTA-502, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 502.4022, having the molecular formula of C₃₂H₅₄O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 501: 483, 457, 465 and 439,

GTA-504, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 504.4195, having the molecular formula of C₃₂H₅₆O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 503: 485, 459, 467 and 441,

GTA-512, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 512.4077, having the molecular formula of C₃₀H₅₆O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 511: 493, 315, and 467,

GTA-518, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 518.3974, having the molecular formula of C₃₂H₅₄O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 517: 499, 473, 499, 481 and 445,

GTA-520, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 520.4128, having the molecular formula of C₃₂H₅₆O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 519: 501, 457, 475, 459, 447 and 483,

GTA-522, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 522.4284, having the molecular formula of C₃₂H₅₈O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 521: 503, 459, 477, 504, 441 and 485,

GTA-524, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 524.4441, having the molecular formula of C₃₂H₆₀O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 523: 505, 461, 479, 506, 443 and 487,

GTA-530, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 530.4335, having the molecular formula of C₃₄H₅₈O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 529: 467, 511 and 485,

GTA-532, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 532.4492, having the molecular formula of C₃₄H₆₀O₄, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 531: 513, 469, 487 and 495,

GTA-536, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 536.4077, having the molecular formula of C₃₂H56O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ion of parent [M−H] mass 535: 473,

GTA-538, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 538.4233, having the molecular formula of C₃₂H₅₈O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 537: 519, 475, 493, 501 and 457,

GTA-540, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 540.4389, having the molecular formula of C₃₂H₆₀O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 539: 315, 521, 495 and 477,

GTA-550, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 550.4597, having the molecular formula of C₃₄H₆₂O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 549: 487, 531, 251, 253, 513, 469 and 506,

GTA-574, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 574.4597, having the molecular formula of C₃₆H₆₂O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 573: 295, 223, 555 and 511,

GTA-576, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 576.4754, having the molecular formula of C₃₆H₆₄O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 575: 277, 297, 557, 513 and 495,

GTA-580, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 580.5067, having the molecular formula of C₃₆H₆₈O₅, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 579: 561, 543, 535, 517 and 499,

GTA-590, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 590.4546, having the molecular formula of C₃₆H₆₂O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ion of parent [M−H] mass 589: 545,

GTA-592, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 592.4703, having the molecular formula of C₃₆H₆₄O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 591: 555 and 113,

GTA-594, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 594.4859, having the molecular formula of C₃₆H₆₆O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 593: 557 371, 315 and 277, and

GTA-596, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 596.5016, having the molecular formula of C₃₆H₆₈O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 595: 279, 315, 297, 577 and 559.

For example, the GTA dicarboxylic fatty acid metabolite may be GTA-446, which has the formula C₂₈H₄₆O₄and the structure:

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There is also provided herein a method for determining gastrointestinal inflammation status within the body of a mammalian subject. The method comprises measuring circulating levels of one or more GTA dicarboxylic fatty acid metabolite, wherein the GTA dicarboxylic fatty acid metabolite is a dicarboxylic fatty acid between 28 and 36 carbons comprised of a dimeric fatty acid structure of two shorter chains ranging between 14 and 18 carbons in length joined by a single or double bond, and if a level one or more of these GTA dicarboxylic fatty acid metabolites is detected to be lower than a predetermined control level, an earlier test value for the subject, or a normal level for healthy subjects, the subject is assessed as having or being at risk for gastrointestinal inflammation.

In further embodiments of the method, the GTA dicarboxylic fatty acid metabolite may be one of the following: GTA-446, GTA-448, GTA-450, GTA-452, GTA-464, GTA-466, GTA-468, GTA-474, GTA-476, GTA-478, GTA-484, GTA-490, GTA-492, GTA-494, GTA-502, GTA-504, GTA-512, GTA-518, GTA-520, GTA-522, GTA-524, GTA-530, GTA-532, GTA-536, GTA-538, GTA-540, GTA-550, GTA-574, GTA-576, GTA-580, GTA-590, GTA-592, GTA-594, and GTA-596.

In further non-limiting embodiments, the GTA dicarboxylic fatty acid metabolite may have a molecular formula of C₂₈H₄₆O₄(GTA-446), C₂₈H₄₈O₄(GTA-448), C₂₈H₅₀O₄(GTA-450), C₂₈H₅₂O₄(GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), C₂₈H₅₂O(GTA-468), C₃₀H₅₀O₄(GTA-474), C₃₀H₅₂O₄GTA-476, C₃₀H₅₄O₄(GTA-478), C₂₈H₅₂O₆(GTA-484), C₃₀H₅₀O₅(GTA-490), C₃₀H₅₂O(GTA-492), C₃₀H₅₄O₅(GTA-494), C₃₂H₅₄O₄(GTA-502), C₃₂H₅₆O₄(GTA-504), C₃₀H₅₆O₆(GTA-512), C₃₂H₅₄O₅(GTA-518), C₃₂H₅₆O₅(GTA-520), C₃₂H₅₈O₅(GTA-522), C₃₂H₆₀O₅GTA-524, C₃₄H₅₈O₄(GTA-530), C₃₄H₆₀O₄(GTA-532), C₃₂H₅₆O₆(GTA-536), C₃₂H₅₈O₆(GTA-538), C₃₂H₆₀O₆(GTA-540), C₃₄H₆₂O₅(GTA-550), C₃₆H₆₂O₅(GTA-574), C₃₆H₆₄O₅(GTA-576), C₃₆H₆₈O₅(GTA-580), C₃₆H₆₂O₆(GTA-590), C₃₆H₆₄O₆(GTA-592), C₃₆H₆₆O₆(GTA-594), or C₃₆H₆₈O₆(GTA-596).

GTA-468, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 468.3814, having the molecular formula of C₂₈H₅₂O, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 467: 449, 423, and 405,

GTA-536, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 536.4077, having the molecular formula of C₃₂H₅₆O₆, and characterized by a OD MS/MS fragmentation pattern using N₂as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ion of parent [M−H] mass 535: 473,

In one specific embodiment, the GTA dicarboxylic fatty acid metabolite may be GTA-446, which has the formula C₂₈H₄₆O₄and the structure:

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Also provided herein is a kit for detecting and treating a gastric tract acid (GTA) insufficiency in a mammalian subject. The kit comprises:

a blood specimen collection device for collecting a blood sample from the mammalian subject,

packaging and instructions for submitting the blood sample to a central processing facility to test levels in the blood sample of one or more GTA dicarboxylic fatty acid metabolite, wherein the GTA dicarboxylic fatty acid metabolite is a dicarboxylic fatty acid between 28 and 36 carbons comprised of a dimeric fatty acid structure of two shorter chains ranging between 14 and 18 carbons in length joined by a single or double bond; and

instructions for obtaining the results of testing the blood sample from the central processing facility, wherein in the case of a positive test result comprising a detected low GTA level, a GTA-augmenting anti-inflammatory prebiotic, probiotic, or synthetic GTA product is provided.

In certain embodiments of the kit, the GTA-augmenting anti-inflammatory prebiotic, probiotic, or synthetic GTA product is a composition comprising at least one live or attenuated culture containing a microbial species selected from the genus Blautia, species Faecalibacterium prausnitzii, genus Bacteroides, family Ruminococcaceae, family Lachnospiraceae, genus Coprococcus, genus Roseburia, genus Oscillospira, species Ruminococcus bromii, genus Ruminococcus, family Costridiaceae, species Dorea formicigenerans, species Bacteroides uniformis, genus Dorea, genus Streptococcus, order Clostridiales, genus Anaerostipes, genus Dialister, species Bifidobacterium adolescentis, family Coriobacteriaceae, genus Faecalibacterium, genus Sutterella, species Bacteroides ovatus, genus Parabacteroides, genus Ruminococcus, species Bacteroides faecis, species Eubacterium biforme, genus Phascolartobacterium, and family Enterobacteriaceae; or a prebiotic composition which increases growth and/or viability of the microbial species in the gut; and when administered to the subject the composition increases the synthesis of at least one GTA dicarboxylic fatty acid metabolite in the subject.

In further embodiments, the composition is provided if the levels of the one or more GTA dicarboxylic fatty acid metabolites in the subject are determined to be lower than a predetermined control level, an earlier test value for said subject, or a normal level for healthy subjects. In one particular example, the control may be a predetermined threshold value for the at least one GTA dicarboxylic fatty acid metabolite.

In yet further embodiments, the composition may comprise a live or attenuated culture of a microbial species from the genus Blautia, a live or attenuated culture of Faecalibacterium prausnitzii, or a combination thereof, within a pharmaceutically-acceptable carrier suitable for administration to the gastrointestinal tract of the subject.

In further embodiments of the kit, the GTA dicarboxylic fatty acid metabolite may be one of the following: GTA-446, GTA-448, GTA-450, GTA-452, GTA-464, GTA-466, GTA-468, GTA-474, GTA-476, GTA-478, GTA-484, GTA-490, GTA-492, GTA-494, GTA-502, GTA-504, GTA-512, GTA-518, GTA-520, GTA-522, GTA-524, GTA-530, GTA-532, GTA-536, GTA-538, GTA-540, GTA-550, GTA-574, GTA-576, GTA-580, GTA-590, GTA-592, GTA-594, and GTA-596.

In further non-limiting embodiments, the GTA dicarboxylic fatty acid metabolite may have a molecular formula of C₂₈H₄₆O₄(GTA-446), C₂₈H₄₈O₄(GTA-448), C₂₈H₅₀O₄(GTA-450), C₂₈H₅₂O₄(GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), C₂₈H₅₂O(GTA-468), C₃₀H₅₀O₄(GTA-474), C₃₀H₅₂O₄GTA-476, C₃₄H₅₄O₄(GTA-478), C₂₈H₅₂O₆(GTA-484), C₃₀H₅₀O₅(GTA-490), C₃₀H₅₂O₅(GTA-492), C₃₄H₅₄O₅(GTA-494), C₃₂H₅₄O₄(GTA-502), C₃₂H₅₆O₄(GTA-504), C₃₀H₅₆O₆(GTA-512), C₃₂H₅₄O₅(GTA-518), C₃₂H₅₆O₅(GTA-520), C₃₂H₅₈O₅(GTA-522), C₃₂H₆₀O₅GTA-524, C₃₄H₅₈O₄(GTA-530), C₃₄H₆₀O₄(GTA-532), C₃₂H₅₆O₆(GTA-536), C₃₂H₅₈O₆(GTA-538), C₃₂H₆₀O₆(GTA-540), C₃₄H₆₂O₅(GTA-550), C₃₆H₆₂O₅(GTA-574), C₃₆H₆₄O₅(GTA-576), C₃₆H₆₈O₅(GTA-580), C₃₆H₆₂O₆(GTA-590), C₃₆H₆₄O₆(GTA-592), C₃₆H₆₆O₆(GTA-594), or C₃₆H₆₈O₆(GTA-596).

In one particular example of this kit, the GTA dicarboxylic fatty acid metabolite is GTA-446, having the formula C₂₈H₄₆O₄and the structure:

embedded image

In accordance with further embodiments of the above described methods and kit, the gastric tract acid (GTA) insufficiency may be an indicator of a gastrointestinal (GI) inflammatory state.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features of the invention will become more apparent from the following description in which reference is made to the appended drawings wherein:

FIG. 1 illustrates the mechanism provided herein by which compromised GTA levels as a results of altered microbiome composition can lead to inflammation and cancer development.

FIG. 2 illustrates a schematic diagram of a personalized GTA testing and treatment method described herein; and

FIG. 3 shows a graph of the operational taxonomic units (OTUs) representing particular genus and species-level microbes associated with low or high GTA levels.

FIG. 4 shows a graph illustrating production of GTA 445.4/383.4 (also described herein as GTA 446) by gut microbes in humans and animals (dog and pig).

FIG. 5 shows a graph illustrating production of GTA 447.4/385.4 (also described herein as GTA 448) by gut microbes in humans and animals (dog and pig).

FIG. 6 shows a graph illustrating production of GTA 449.4/405.4 (also described herein as GTA 450) by gut microbes in humans and animals (dog and pig).

FIG. 7 shows a graph illustrating production of GTA 463.4/419.4 (also described herein as GTA 464) by gut microbes in humans and animals (dog and pig).

FIG. 8 shows a graph illustrating production of GTA 465.4/403.4 (also described herein as GTA 466) by gut microbes in humans and animals (dog and pig).

FIG. 9 shows a graph illustrating production of GTA 467.4/423.4 (also described herein as GTA 468) by gut microbes in humans and animals (dog and pig).

DETAILED DESCRIPTION

Gastric tract acids (GTAs) are shown herein to be produced by specific gut microbes. Changes in the microbiome over time may thus result in compromised ability to produce GTAs.

As illustrated in FIG. 1, GTA metabolites are involved in protecting against chronic inflammation through the downregulation of NFκB, as shown in the left-hand panel. Under this state, a relatively low level of NF-κB expression is maintained by adequate GTA levels in the body as a result of optimal microbiome composition. When levels of GTAs become deficient (right panel) due to altered microbiome composition, changes in the relative abundances of particular microbial species, or changes in diversity, NFκB expression is no longer suppressed resulting in the induction of multiple proinflammatory proteins. This creates an oxidative environment in the gastrointestinal tract that can lead to DNA mutations in cells, and ultimately increased cancer risk. GTA deficiency is therefore not a tumor marker like occult blood or methylated DNA; but rather pre-a disease metabolic deficiency that results in a pro-cancer environment within the body.

Based on this new understanding of the role of gut microbes in GTA production, a method is provided herein to increase GTA levels in the body through either augmentation of particular strains with a pre or probiotic approach, or administration of purely synthetic GTAs.

Using the described method to increase GTA levels also represents a novel approach for reducing inflammation within the gastrointestinal tract.

In particular, it has been found that microbial species from the genus Blautia, species Faecalibacterium prausnitzii, genus Bacteroides, family Ruminococcaceae, family Lachnospiraceae, genus Coprococcus, genus Roseburia, genus Oscillospira, species Ruminococcus bromii, genus Ruminococcus, family Costridiaceae, species Dorea formicigenerans, species Bacteroides uniformis, genus Dorea, genus Streptococcus, order Clostridiales, genus Anaerostipes, genus Dialister, species Bifidobacterium adolescentis, family Coriobacteriaceae, genus Faecalibacterium, genus Sutterella, species Bacteroides ovatus, genus Parabacteroides, genus Ruminococcus, species Bacteroides faecis, species Eubacterium biforme, genus Phascolartobacterium, and family Enterobacteriaceae are important for GTA biosynthesis in the gut. Administering a therapeutically-effective amount of a composition comprising at least one live or attenuated culture of at least one of these microbial species, or a prebiotic composition which increases growth and/or viability of the microbial species in the gut, therefore provides a means to increase GTA synthesis in an individual. The subject may be a mammal, in particular a human subject.

In most embodiments, the GTA will be a dicarboxylic fatty acid between 28 and 36 carbons comprised of a dimeric fatty acid structure of two shorter chains ranging between 14 and 18 carbons in length joined by a single or double bond. For example, the GTA dicarboxylic fatty acid metabolite may be GTA-446, which has the formula C₂₈H₄₆O₄and the structure:

embedded image

Other examples of these GTAs include GTA-448, GTA-450, GTA-452, GTA-464, GTA-466, GTA-468, GTA-474, GTA-476, GTA-478, GTA-484, GTA-490, GTA-492, GTA-494, GTA-502, GTA-504, GTA-512, GTA-518, GTA-520, GTA-522, GTA-524, GTA-530, GTA-532, GTA-536, GTA-538, GTA-540, GTA-550, GTA-574, GTA-576, GTA-580, GTA-590, GTA-592, GTA-594, and GTA-596.

Levels of these GTAs can be measured in a variety of ways, including mass spectrometric methods. For example, they may each be identified or measured based on the detection of one or more daughter ion fragment resulting from collision induced dissociation (OD) tandem mass spectrometry. The fragments for each GTA listed above are listed in the following tables.

Although the complete OD fragmentation patterns described below represent unique fingerprints of these target analytes, one will appreciate that not every daughter fragment ion needs to be detected to practice the described methods. In fact, one will appreciate that any number or combination of daughter ion masses could be selected for the purpose of specifically detecting and measuring levels of the parent analyte in a sample. One will further appreciate that the selection of appropriate daughter ions is dependent on multiple criteria such as signal-to-noise ratio, specificity of the transition for the selected analyte, reproducibility of signal, interferences across various matrices, complexity and anticipated specificity of the neutral loss to the parent structure, and more. In many cases, a single daughter fragment ion can be selected based on these criteria and used to quantify the corresponding parent analyte.

GTA Dicarboxylic Fatty Acid Metabolites:
446.3396 (GTA-446):

446.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

401

10.3333
100

445

8.1667
79.0323

427

4.5
43.5484

83
2.8333
27.4194

223
2.5
24.1935

222
2.1667
20.9677

205
1.8333
17.7419

383

1.8333
17.7419

59
1.6667
16.129

97
1
9.6774

81
0.6667
6.4516

109
0.6667
6.4516

203
0.6667
6.4516

221
0.6667
6.4516

409

0.6667
6.4516

123
0.5
4.8387

177
0.5
4.8387

233
0.5
4.8387

259
0.5
4.8387

428
0.5
4.8387

The metabolite 446.3396 (GTA-446) has the molecular formula C₂₈H₄₆O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. For detection and measurement purposes, however, a subset or even one of these fragments will be far more practical. Thus, in certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 445: 427, 409, 401, and 383. In certain preferred embodiments, nominal parent/daughter mass 445/401 or 445/383 may be used for measuring GTA-446 levels.

448.3553 (GTA-448):

448.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

403
3.75
100

429

1.75
46.6667

447

1.5
40

385

1
26.6667

83
0.75
20

447
0.75
20

111
0.5
13.3333

151
0.5
13.3333

402
0.5
13.3333

411

0.5
13.3333

429

0.5
13.3333

59
0.25
6.6667

69
0.25
6.6667

74
0.25
6.6667

81
0.25
6.6667

187
0.25
6.6667

223
0.25
6.6667

279
0.25
6.6667

386
0.25
6.6667

404
0.25
6.6667

The metabolite 448.3553 (GTA-448) has the molecular formula C₂₈H₄₈O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. For detection and measurement purposes, however, a subset or even one of these fragments will be far more practical. Thus, in certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 447: 429, 411, 403, and 385. In certain preferred embodiments, nominal parent/daughter mass 447/385 may be used for measuring GTA-448 levels.

450.3709 (GTA-450):

450.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

431

19
100

449

15.25
80.2632

405

10
52.6316

387

4.5
23.6842

405

1.5
7.8947

111
1.25
6.5789

413

1.25
6.5789

432
1
5.2632

59
0.75
3.9474

71
0.75
3.9474

97
0.75
3.9474

281
0.75
3.9474

406
0.75
3.9474

450
0.75
3.9474

57
0.5
2.6316

83
0.5
2.6316

123
0.5
2.6316

125
0.5
2.6316

181
0.5
2.6316

233
0.5
2.6316

The metabolite 450.3709 (GTA-450) has the molecular formula C₂₈H₅₀O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 449: 431, 413, 405, and 387. In certain preferred embodiments, nominal parent/daughter mass 449/405 may be used for measuring GTA-450 levels.

452.3866 (GTA-452):

452.4

CE: −35 V

m/z (amu)

451(M − H+)

433

407

389

281

279

183

169

153

139

125

111

97

The metabolite 452.3866 (GTA-452) has the molecular formula C₂₈H₅₂O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 451: 433, 407, and 389. In certain preferred embodiments, nominal parent/daughter mass 451/407 may be used for measuring GTA-452 levels.

464.3522 (GTA-464):

464.4

CE: −35 V

m/z (amu)

463(M − H+)

445

419

401

383

315

297

241

The metabolite 464.3522 (GTA-464) has the molecular formula C₂₈H₄₈O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 463: 445, 419, 401, and 383. In certain preferred embodiments, nominal parent/daughter mass 463/419 may be used for measuring GTA-464 levels.

466.3661 (GTA-466):

466.4

CE: −35 V

m/z (amu)

465(M − H+)

447

433

421

405

403

349

297

279

241

223

185

The metabolite 466.3661 (GTA-466) has the molecular formula C₂₈H₅₀O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 465: 447, 421, and 403. In certain preferred embodiments, nominal parent/daughter mass 465/403 may be used for measuring GTA-466 levels.

468.3814 (GTA-468):

468.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

449

10.5
100

467

7.5
71.4286

187
4
38.0952

449

2
19.0476

263
1.5
14.2857

423

1.5
14.2857

141
1.25
11.9048

279
1.25
11.9048

169
1
9.5238

450
1
9.5238

215
0.75
7.1429

297
0.75
7.1429

405

0.75
7.1429

468
0.75
7.1429

185
0.5
4.7619

188
0.5
4.7619

213
0.5
4.7619

251
0.5
4.7619

281
0.5
4.7619

113
0.25
2.381

The metabolite 468.3814 (GTA-468) has the molecular formula C₂₈H₅₂Oand can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 467: 449, 423, and 405. In certain preferred embodiments, nominal parent/daughter mass 467/423 may be used for measuring GTA-468 levels.

474.3736 (GTA-474):

474.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

473

1.8
100

455

1.05
58.3333

85
0.45
25

113
0.45
25

455

0.35
19.4444

57
0.15
8.3333

71
0.15
8.3333

97
0.15
8.3333

117
0.15
8.3333

222
0.15
8.3333

456
0.15
8.3333

474
0.15
8.3333

411

0.7
38.8889

429

0.6
33.3333

75
0.5
27.7778

474
0.3
16.6667

474
0.3
16.6667

223
0.2
11.1111

429
0.2
11.1111

59
0.1
5.5556

The metabolite 474.3736 (GTA-474) has the molecular formula C₃₀H₅₀O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 473: 455, 429, and 411. In certain preferred embodiments, nominal parent/daughter mass 473/429 may be used for measuring GTA-474 levels.

476.3866 (GTA-476):

476.5

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

475

4.1818
100

457

2.9091
69.5652

431

1.5455
36.9565

413

0.8182
19.5652

279
0.4545
10.8696

439

0.3636
8.6957

458
0.3636
8.6957

458
0.3636
8.6957

476
0.2727
6.5217

57
0.1818
4.3478

59
0.1818
4.3478

83
0.1818
4.3478

97
0.1818
4.3478

111
0.1818
4.3478

123
0.1818
4.3478

235
0.1818
4.3478

251
0.1818
4.3478

414
0.1818
4.3478

432
0.1818
4.3478

71
0.0909
2.1739

The metabolite 476.3866 (GTA-476) has the molecular formula C₃₀H₅₂O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 475: 457, 431, 439 and 413. In certain preferred embodiments, nominal parent/daughter mass 475/431 may be used for measuring GTA-476 levels.

478.4022 (GTA-478):

478.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

477

7.4286
100

459

5.2857
71.1538

433

2
26.9231

415

1.6429
22.1154

478
0.7857
10.5769

434
0.5
6.7308

460
0.5
6.7308

125
0.3571
4.8077

281
0.3571
4.8077

97
0.2857
3.8462

111
0.2857
3.8462

435
0.2857
3.8462

59
0.2143
2.8846

123
0.2143
2.8846

223
0.2143
2.8846

416
0.2143
2.8846

434
0.2143
2.8846

435
0.2143
2.8846

441

0.2143
2.8846

477
0.2143
2.8846

The metabolite 478.4022 (GTA-478) has the molecular formula C₃₀H₅₄O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 477: 459, 433, 441 and 415. In certain preferred embodiments, nominal parent/daughter mass 477/433 may be used for measuring GTA-478 levels.

484.3764 (GTA-484):

484.4

CE: −40 V

m/z (amu)
intensity (counts)
% intensity

315

1.8333
100

123
0.8333
45.4545

297
0.8333
45.4545

185
0.6667
36.3636

465

0.6667
36.3636

279
0.5
27.2727

439

0.5
27.2727

483

0.5
27.2727

171
0.3333
18.1818

187
0.3333
18.1818

201
0.3333
18.1818

223
0.3333
18.1818

241
0.3333
18.1818

295
0.3333
18.1818

313
0.3333
18.1818

315
0.3333
18.1818

421

0.3333
18.1818

447

0.3333
18.1818

101
0.1667
9.0909

111
0.1667
9.0909

The metabolite 484.3764 (GTA-484) has the molecular formula C₂₈H₅₂O₆and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 483: 465, 315, 439, 483, 421, and 447. In certain preferred embodiments, nominal parent/daughter mass 483/315 may be used for measuring GTA-484 levels.

490.3658 (GTA-490):

490.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

489

1.1739
100

319

0.413
35.1852

445

0.3696
31.4815

241
0.3478
29.6296

471

0.3478
29.6296

427

0.1957
16.6667

113
0.1739
14.8148

195
0.1739
14.8148

223
0.1739
14.8148

249
0.1739
14.8148

490
0.1739
14.8148

97
0.1522
12.963

267
0.1522
12.963

345
0.1304
11.1111

57
0.1087
9.2593

101
0.1087
9.2593

143
0.1087
9.2593

265
0.1087
9.2593

373
0.1087
9.2593

472
0.1087
9.2593

The metabolite 490.3658 (GTA-490) has the molecular formula C₃₀H₅₀O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 489: 445, 471, 427 and 319. In certain preferred embodiments, nominal parent/daughter mass 489/445 may be used for measuring GTA-490 levels.

492.3815 (GTA-492):

492.4

CE: −40 V

m/z (amu)
intensity (counts)
% intensity

241

4.3077
100

249

2.6923
62.5

267

2.4615
57.1429

97
1.8462
42.8571

473

1.3846
32.1429

223
1.1538
26.7857

195
1
23.2143

143
0.9231
21.4286

447

0.9231
21.4286

101
0.8462
19.6429

491

0.8462
19.6429

113
0.7692
17.8571

319
0.6923
16.0714

57
0.5385
12.5

59
0.4615
10.7143

213
0.4615
10.7143

167
0.3846
8.9286

171
0.3846
8.9286

179
0.3846
8.9286

193
0.3846
8.9286

The metabolite 492.3815 (GTA-492) has the molecular formula C₃₀H₅₂Oand can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 491: 241, 249, 267, 473, and 447. In certain preferred embodiments, nominal parent/daughter mass 491/241 may be used for measuring GTA-492 levels.

494.3971 (GTA-494):

494.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

493

3
100

475

2.6667
88.8889

215

1.6667
55.5556

195
1.3333
44.4444

213
1.3333
44.4444

449

1
33.3333

167
0.6667
22.2222

171
0.6667
22.2222

241
0.6667
22.2222

267
0.6667
22.2222

279
0.6667
22.2222

297
0.6667
22.2222

307
0.6667
22.2222

431
0.6667
22.2222

494
0.6667
22.2222

494
0.6667
22.2222

113
0.3333
11.1111

141
0.3333
11.1111

151
0.3333
11.1111

197
0.3333
11.1111

The metabolite 494.3971 (GTA-494) has the molecular formula C₃₀H₅₄O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 493: 475, 215, and 449. In certain preferred embodiments, nominal parent/daughter mass 493/449 may be used for measuring GTA-494 levels.

502.4022 (GTA-502):

502.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

483

1.0435
100

501

0.913
87.5

439

0.7391
70.8333

457

0.5217
50

502
0.2609
25

279
0.1739
16.6667

458
0.1739
16.6667

484
0.1739
16.6667

502
0.1739
16.6667

59
0.1304
12.5

109
0.1304
12.5

111
0.1304
12.5

123
0.1304
12.5

196
0.1304
12.5

221
0.1304
12.5

222
0.1304
12.5

277
0.1304
12.5

317
0.1304
12.5

440
0.1304
12.5

465

0.1304
12.5

The metabolite 502.4022 (GTA-502) has the molecular formula C₃₂H₅₄O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 501: 483, 457, 465 and 439. In certain preferred embodiments, nominal parent/daughter mass 501/457 may be used for measuring GTA-502 levels.

504.4195 (GTA-504):

504.4

CE: −40 V

m/z (amu)
intensity (counts)
% intensity

485

5.8947
100

503

4.0526
68.75

441

2.5789
43.75

459

1.2105
20.5357

486
0.6842
11.6071

97
0.4211
7.1429

111
0.3684
6.25

467

0.3158
5.3571

504
0.3158
5.3571

57
0.2632
4.4643

223
0.2632
4.4643

263
0.2632
4.4643

377
0.2632
4.4643

442
0.2632
4.4643

169
0.2105
3.5714

279
0.2105
3.5714

329
0.2105
3.5714

59
0.1579
2.6786

71
0.1579
2.6786

83
0.1579
2.6786

The metabolite 504.4195 (GTA-504) has the molecular formula C₃₂H₅₆O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 503: 485, 459, 467 and 441. In certain preferred embodiments, nominal parent/daughter mass 503/459 may be used for measuring GTA-504 levels.

512.4077 (GTA-512):

512.4

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

315

12
100

511

8.5
70.8333

151
2.3333
19.4444

213
1.8333
15.2778

297
1.5
12.5

493

1.3333
11.1111

195
1
8.3333

279
1
8.3333

512
0.8333
6.9444

512
0.6667
5.5556

141
0.5
4.1667

171
0.5
4.1667

313
0.5
4.1667

467

0.5
4.1667

169
0.3333
2.7778

177
0.3333
2.7778

231
0.3333
2.7778

251
0.3333
2.7778

259
0.3333
2.7778

314
0.3333
2.7778

The metabolite 512.4077 (GTA-512) has the molecular formula C₃₀H₅₆O₆and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 511: 493, 315, and 467. In certain preferred embodiments, nominal parent/daughter mass 511/315 may be used for measuring GTA-512 levels.

518.3974 (GTA-518):

518.4

CE: −40 V

m/z (amu)
intensity (counts)
% intensity

517

0.8182
100

499

0.5909
72.2222

115
0.4091
50

455

0.3636
44.4444

171
0.3182
38.8889

171
0.3182
38.8889

473

0.2727
33.3333

59
0.2273
27.7778

401
0.2273
27.7778

499

0.2273
27.7778

113
0.1818
22.2222

389
0.1818
22.2222

437
0.1818
22.2222

481

0.1818
22.2222

71
0.1364
16.6667

111
0.1364
16.6667

125
0.1364
16.6667

203
0.1364
16.6667

223
0.1364
16.6667

445

0.1364
16.6667

The metabolite 518.3974 (GTA-518) has the molecular formula C₃₂H₅₄O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 517: 499, 473, 499, 481 and 445. In certain preferred embodiments, nominal parent/daughter mass 517/473 may be used for measuring GTA-518 levels.

520.4128 (GTA-520):

520.4

CE: −42 V

m/z (amu)
intensity (counts)
% intensity

501

2.2353
100

519

1.3824
61.8421

457

0.8235
36.8421

475

0.6176
27.6316

115
0.4118
18.4211

59
0.3529
15.7895

83
0.3529
15.7895

459

0.3529
15.7895

502
0.3529
15.7895

241
0.3235
14.4737

297
0.2647
11.8421

71
0.2353
10.5263

195
0.2353
10.5263

223
0.2353
10.5263

279
0.2353
10.5263

447

0.2353
10.5263

483

0.2353
10.5263

97
0.2059
9.2105

111
0.2059
9.2105

221
0.2059
9.2105

The metabolite 520.4128 (GTA-520) has the molecular formula C₃₂H₅₆O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 519: 501, 457, 475, 459, 447 and 483. In certain preferred embodiments, nominal parent/daughter mass 519/475 may be used for measuring GTA-520 levels.

522.4284 (GTA-522):

522.4

CE: −40 V

m/z (amu)
intensity (counts)
% intensity

521

1.375
100

503

1.2917
93.9394

459

0.375
27.2727

241
0.3333
24.2424

477

0.3333
24.2424

504

0.25
18.1818

111
0.2083
15.1515

115
0.2083
15.1515

171
0.2083
15.1515

267
0.2083
15.1515

297
0.2083
15.1515

441

0.2083
15.1515

223
0.1667
12.1212

269
0.1667
12.1212

271
0.1667
12.1212

279
0.1667
12.1212

485

0.1667
12.1212

522
0.1667
12.1212

57
0.125
9.0909

59
0.125
9.0909

The metabolite 522.4284 (GTA-522) has the molecular formula C₃₂H₅₈O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 521: 503, 459, 477, 504, 441 and 485. In certain preferred embodiments, nominal parent/daughter mass 521/477 may be used for measuring GTA-522 levels.

524.4441 (GTA-524):

524.4

CE: −40 V

m/z (amu)

523

505

487

479

463

461

443

365

337

299

297

281

279

271

269

253

251

243

225

197

171

169

157

155

143

141

139

127

125

123

115

113

111

83

The metabolite 524.4441 (GTA-524) has the molecular formula C₃₂H₆₀O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 523: 505, 461, 479, 506, 443 and 487. In certain preferred embodiments, nominal parent/daughter mass 523/461 may be used for measuring GTA-524 levels.

530.4335 (GTA-530):

530.4

CE: −40 V

m/z (amu)
intensity (counts)
% intensity

529

1.1563
100

467

0.8125
70.2703

511

0.8125
70.2703

530
0.2188
18.9189

85
0.1563
13.5135

485

0.1563
13.5135

512

0.1563
13.5135

512
0.1563
13.5135

75
0.125
10.8108

468
0.125
10.8108

177
0.0938
8.1081

250
0.0938
8.1081

251
0.0938
8.1081

530
0.0938
8.1081

59
0.0625
5.4054

97
0.0625
5.4054

109
0.0625
5.4054

113
0.0625
5.4054

195
0.0625
5.4054

205
0.0625
5.4054

The metabolite 530.4335 (GTA-530) has the molecular formula C₃₄H₅₈O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 529: 467, 511 and 485. In certain preferred embodiments, nominal parent/daughter mass 529/467 may be used for measuring GTA-530 levels.

532.4492 (GTA-532):

532.5

CE: −42 V

m/z (amu)
intensity (counts)
% intensity

513

1.375
100

469

1.25
90.9091

531

0.9375
68.1818

195
0.25
18.1818

470
0.25
18.1818

470
0.25
18.1818

111
0.1875
13.6364

181
0.1875
13.6364

251
0.1875
13.6364

487

0.1875
13.6364

514
0.1875
13.6364

532
0.1875
13.6364

59
0.125
9.0909

71
0.125
9.0909

97
0.125
9.0909

113
0.125
9.0909

127
0.125
9.0909

495

0.125
9.0909

514
0.125
9.0909

532
0.125
9.0909

The metabolite 532.4492 (GTA-532) has the molecular formula C₃₄H₆₀O₄and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 531: 513, 469, 487 and 495. In certain preferred embodiments, nominal parent/daughter mass 531/469 may be used for measuring GTA-532 levels.

536.4077 (GTA-536):

MS/MS transition 535/473

The metabolite 536.4077 (GTA-536) has the molecular formula C₃₂H₅₆O₆and can be characterized by the MS/MS transition shown above. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize one or more of the observed daughter ions (nominal masses): These include the following daughter ion of parent [M−H] mass 535: 473. In a preferred embodiments, nominal parent/daughter mass 535/573 may be used for measuring GTA-590 levels.

538.4233 (GTA-538):

538.4

CE: −40 V

m/z (amu)
intensity (counts)
% intensity

537

1.6667
100

519

1
60

475

0.6667
40

493

0.4444
26.6667

59
0.3333
20

115
0.3333
20

333
0.3333
20

501

0.3333
20

520
0.3333
20

538
0.3333
20

101
0.2222
13.3333

315
0.2222
13.3333

457

0.2222
13.3333

538
0.2222
13.3333

538
0.2222
13.3333

71
0.1111
6.6667

143
0.1111
6.6667

171
0.1111
6.6667

179
0.1111
6.6667

221
0.1111
6.6667

The metabolite 538.4233 (GTA-538) has the molecular formula C₃₂H₅₈O₆and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 537: 519, 475, 493, 501 and 457. In certain preferred embodiments, nominal parent/daughter mass 537/475 may be used for measuring GTA-538 levels.

540.4389 (GTA-540):

540.5

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

315

24.6
100

539

15.6
63.4146

223
2.4
9.7561

179
2.2
8.9431

521

1.8
7.3171

297
1.2
4.878

495

1.2
4.878

477

0.8
3.252

540
0.8
3.252

241
0.6
2.439

259
0.6
2.439

316
0.6
2.439

540
0.6
2.439

125
0.4
1.626

171
0.4
1.626

225
0.4
1.626

257
0.4
1.626

279
0.4
1.626

313
0.4
1.626

314
0.4
1.626

The metabolite 540.4389 (GTA-540) has the molecular formula C₃₂H₆₀O₆and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 539: 315, 521, 495 and 477. In certain preferred embodiments, nominal parent/daughter mass 539/315 may be used for measuring GTA-540 levels.

550.4597 (GTA-550):

550.5

CE: −42 V

m/z (amu)
intensity (counts)
% intensity

487

1
100

549

0.9286
92.8571

531

0.7857
78.5714

251

0.5714
57.1429

253

0.5714
57.1429

111
0.4286
42.8571

125
0.4286
42.8571

269
0.4286
42.8571

271
0.4286
42.8571

277
0.4286
42.8571

513

0.4286
42.8571

71
0.3571
35.7143

171
0.3571
35.7143

297
0.3571
35.7143

469

0.3571
35.7143

115
0.2857
28.5714

279
0.2857
28.5714

295
0.2857
28.5714

433
0.2857
28.5714

506

0.2857
28.5714

The metabolite 550.4597 (GTA-550) has the molecular formula C₃₄H₆₂O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 549: 487, 531, 251, 253, 513, 469 and 506. In certain preferred embodiments, nominal parent/daughter mass 549/487 may be used for measuring GTA-550 levels.

574.4597 (GTA-574):

574.5

CE: −42 V

m/z (amu)
intensity (counts)
% intensity

573.4742
1.0571
100

295.2386
0.7143
67.5676

555.4666
0.5714
54.0541

125.1053
0.4857
45.9459

279.2508
0.4857
45.9459

171.1051
0.4571
43.2432

223.1408
0.4286
40.5405

511.4199
0.4
37.8378

157.085
0.3429
32.4324

493.4546
0.3429
32.4324

183.1039
0.2857
27.027

277.2282
0.2571
24.3243

293.2359
0.2571
24.3243

401.3605
0.2286
21.6216

113.0966
0.2
18.9189

293.2102
0.2
18.9189

429.3752
0.2
18.9189

249.2203
0.1714
16.2162

385.3457
0.1714
16.2162

389.3651
0.1714
16.2162

The metabolite 574.4597 (GTA-574) has the molecular formula C₃₆H₆₂O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 573: 295, 223, 555 and 511. In certain preferred embodiments, nominal parent/daughter mass 573/223 may be used for measuring GTA-574 levels.

576.4754 (GTA-576):

576.5

CE: −42 V

m/z (amu)
intensity (counts)
% intensity

575

2.9048
100

277

1.4286
49.1803

297

1.4286
49.1803

557

1.2381
42.623

513

0.9524
32.7869

279
0.8095
27.8689

171
0.7619
26.2295

183
0.5238
18.0328

295
0.5238
18.0328

125
0.4762
16.3934

403
0.4286
14.7541

111
0.381
13.1148

495

0.381
13.1148

251
0.3333
11.4754

293
0.3333
11.4754

97
0.2857
9.8361

113
0.2857
9.8361

205
0.2857
9.8361

223
0.2857
9.8361

296
0.2857
9.8361

The metabolite 576.4754 (GTA-576) has the molecular formula C₃₆H₆₄O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 575: 277, 297, 557, 513 and 495. In certain preferred embodiments, nominal parent/daughter mass 575/513 may be used for measuring GTA-576 levels.

580.5067 (GTA-580):

580.5

CE: −42 V

m/z (amu)

579

561

543

535

517

499

421

407

389

375

299

297

281

281

279

263

253

185

171

The metabolite 580.5067 (GTA-580) has the molecular formula C₃₆H₆₈O₅and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 579: 561, 543, 535, 517 and 499. In certain preferred embodiments, nominal parent/daughter mass 579/517 may be used for measuring GTA-580 levels.

590.4546 (GTA-590):

MS/MS transition 589/545

The metabolite 590.4546 (GTA-590) has the molecular formula C₃₆H₆₂O₆and can be characterized by the MS/MS transition shown above. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize one or more of the observed daughter ions (nominal masses): These include the following daughter ion of parent [M−H] mass 589: 545. In a preferred embodiments, nominal parent/daughter mass 589/545 may be used for measuring GTA-590 levels.

592.4703 (GTA-592):

592.5

CE: −35 V

m/z (amu)
intensity (counts)
% intensity

555

113

16.1667
100

85
3.3333
20.6186

103
2
12.3711

175
2
12.3711

117
1.6667
10.3093

59
1.3333
8.2474

75
1.3333
8.2474

95
1.3333
8.2474

99
1.3333
8.2474

115
1
6.1856

149
1
6.1856

87
0.8333
5.1546

129
0.8333
5.1546

591

0.8333
5.1546

157
0.6667
4.1237

415
0.6667
4.1237

73
0.5
3.0928

415
0.5
3.0928

71
0.3333
2.0619

89
0.3333
2.0619

The metabolite 592.4703 (GTA-592) has the molecular formula C₃₆H₆₄O₆and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 591: 555 and 113. In certain preferred embodiments, nominal parent/daughter mass 591/555 may be used for measuring GTA-592 levels.

594.4859 (GTA-594):

594.5

CE: −50 V

m/z (amu)
intensity (counts)
% intensity

371

4.2
100

171
3.6
85.7143

315

3.6
85.7143

575

3.6
85.7143

277

3.4
80.9524

201
3
71.4286

295
2.8
66.6667

297
2.8
66.6667

593

2.8
66.6667

279
2.4
57.1429

557

2.2
52.381

141
1.8
42.8571

313
1.6
38.0952

513
1.6
38.0952

557
1.6
38.0952

125
1.4
33.3333

594
1.4
33.3333

576
1.2
28.5714

113
1
23.8095

139
1
23.8095

The metabolite 594.4859 (GTA-594) has the molecular formula C₃₆H₆₆O₆and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 593: 557, 371, 315 and 277. In certain preferred embodiments, nominal parent/daughter mass 593/557 or 593/371 may be used for measuring GTA-594 levels.

596.5016 (GTA-596):

596.5

CE: −50 V

m/z (amu)
intensity (counts)
% intensity

279

53.6
100

315

35.8
66.791

297

21.6
40.2985

313
9.6
17.9104

577

7.4
13.806

281
6.8
12.6866

595

6.2
11.5672

295
3.6
6.7164

171
3.4
6.3433

516
3.2
5.9701

559

2.6
4.8507

125
2.4
4.4776

141
2
3.7313

127
1.8
3.3582

155
1.6
2.9851

169
1.4
2.6119

185
1.4
2.6119

207
1.4
2.6119

280
1.2
2.2388

373
1.2
2.2388

The metabolite 596.5016 (GTA-596) has the molecular formula C₃₆H₆₈O₆and can be characterized by the full CID MS/MS fragmentation pattern shown in the above table. In certain embodiments of analysis using N₂as collision gas and atmospheric pressure chemical ionization (APCI) under negative ionization, it may be preferred to utilize the one or more of the daughter ions (nominal masses) bolded in the table above. These include the following daughter ions of parent [M−H] mass 595: 279, 315, 297, 577 and 559. In certain preferred embodiments, nominal parent/daughter mass 595/559 may be used for measuring GTA-596 levels.

According to the methods described herein, biological samples from a subject may be compared to the same type of sample taken from the normal population to identify differences in the levels of the described GTA biomarkers. The samples can be extracted and analyzed using various analytical platforms including, but not limited to, Fourier transform ion cyclotron resonance mass spectrometry (FTMS) and liquid chromatography mass spectrometry (LC-MS).

The biological samples could originate from anywhere within the body, for example but not limited to, blood (serum/plasma), stool, or biopsy of any solid tissue including tumor, adjacent normal, smooth and skeletal muscle, adipose tissue, liver, skin, hair, brain, kidney, pancreas, lung, colon, stomach, or other. Of particular interest are blood or serum samples. While the term “blood” or “serum” may be used herein, those skilled in the art will recognize that plasma or whole blood or a sub-fraction of whole blood may also be used.

When a blood sample is drawn from a patient there are several ways in which the sample can be processed. The range of processing can be as little as none (i.e. frozen whole blood) or as complex as the isolation of a particular cell type. The most common and routine procedures involve the preparation of either serum or plasma from whole blood. All blood sample processing methods, including spotting of blood samples onto solid-phase supports, such as filter paper or other immobile materials, are also contemplated.

Without wishing to be limiting, the processed blood or plasma sample described above may then be further processed to make it compatible with the methodical analysis technique to be employed in the detection and measurement of the metabolites contained within the processed blood sample. The types of processing can range from as little as no further processing to as complex as differential extraction and chemical derivatization. Extraction methods may include sonication, soxhlet extraction, microwave assisted extraction (MAE), supercritical fluid extraction (SFE), accelerated solvent extraction (ASE), pressurized liquid extraction (PLE), pressurized hot water extraction (PHWE) and/or surfactant assisted extraction (PHWE) in common solvents such as methanol, ethanol, mixtures of alcohols and water, or organic solvents such as ethyl acetate or hexane. A method of particular interest for extracting metabolites for FTMS analysis and for flow injection LC-MS/MS analysis is to perform a liquid/liquid extraction whereby non-polar metabolites dissolve in an organic solvent and polar metabolites dissolve in an aqueous solvent.

The extracted samples may be analyzed using any suitable method including those known in the art. For example, and without wishing to be limiting, extracts of biological samples are amenable to analysis on essentially any mass spectrometry platform, either by direct injection or following chromatographic separation. Typical mass spectrometers are comprised of a source that ionizes molecules within the sample, and a detector for detecting the ionized molecules or fragments of molecules. Non-limiting examples of common sources include electron impact, electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), atmospheric pressure photo ionization (APPI), matrix assisted laser desorption ionization (MALDI), surface enhanced laser desorption ionization (SELDI), and derivations thereof. Common mass separation and detection systems can include quadrupole, quadrupole ion trap, linear ion trap, time-of-flight (TOF), magnetic sector, ion cyclotron (FTMS), Orbitrap, and derivations and combinations thereof. The advantage of FTMS over other MS-based platforms is its high resolving capability that allows for the separation of metabolites differing by only hundredths of a Dalton, many of which would be missed by lower resolution instruments.

By the term “metabolite”, it is meant specific GTA small molecules, the levels or intensities of which are measured in a sample, and that may be used as markers to diagnose a disease state. These small molecules may also be referred to herein as “metabolite marker”, “metabolite component”, “biomarker”, or “biochemical marker”.

The metabolites are generally characterized by their accurate mass, as measured by mass spectrometry technique. The accurate mass may also be referred to as “accurate neutral mass” or “neutral mass”. The accurate mass of a metabolite is given herein in Daltons (Da), or a mass substantially equivalent thereto. By “substantially equivalent thereto”, it is meant that a +/−5 ppm difference in the accurate mass would indicate the same metabolite. The accurate mass is given as the mass of the neutral metabolite. During the ionization of the metabolites, which occurs during analysis of the sample, the metabolite will cause either a loss or gain of one or more hydrogen atoms and a loss or gain of an electron. This changes the accurate mass to the “ionized mass”, which differs from the accurate mass by the mass of hydrogen atoms and electrons lost or gained during ionization. Unless otherwise specified, the accurate neutral mass will be referred to herein.

Similarly, when a metabolite is described by its molecular formula, the molecular formula of the neutral metabolite will be given. Naturally, the molecular formula of the ionized metabolite will differ from the neutral molecular formula by the number of hydrogen atoms lost or gained during ionization or due to the addition of a non-hydrogen adduct ion.

Data is collected during analysis and quantifying data for one or more than one metabolite is obtained. “Quantifying data” is obtained by measuring the levels or intensities of specific metabolites present in a sample.

The quantifying data is compared to corresponding data from one or more than one reference sample. The “reference sample” is any suitable reference sample for the particular disease state. For example, and without wishing to be limiting in any manner, the reference sample may be a sample from a control individual, i.e., a person not suffering from GI inflammation and/or cancer with or without a family history of GI inflammation and/or cancer (also referred to herein as a “ ‘normal’ counterpart”); the reference sample may also be a sample obtained from a patient clinically diagnosed with GI inflammation and/or cancer. As would be understood by a person of skill in the art, more than one reference sample may be used for comparison to the quantifying data. For example and without wishing to be limiting, the one or more than one reference sample may be a first reference sample obtained from a control individual. In the case of monitoring a subject's change in disease state, the reference sample may include a sample obtained at an earlier time period either pre-therapy or during therapy to compare the change in disease state as a result of therapy.

An “internal control metabolite” refers to an endogenous metabolite naturally present in the patient. Any suitable endogenous metabolite that does not vary over the disease states can be used as the internal control metabolite.

Use of a ratio of the GTA metabolite marker to the internal control metabolite may offer measurement that is more stable and reproducible than measurement of absolute levels of the metabolite marker. As the internal control metabolite is naturally present in all samples and does not appear to vary significantly over disease states, the sample-to-sample variability (due to handling, extraction, etc.) is minimized.

The measurement of GTA metabolite markers according to the methods described herein can in certain embodiments be carried out using assay platforms other than mass spectometric methods. There are multiple types of assay platform options currently available depending on the molecules being detected. These include, but are not limited to, colorimetric chemical assays (UV, or other wavelength), antibody-based enzyme-linked immunosorbant assays (ELISAs), dipstick chemical assays, image analysis such as MRI, petscan, CT scan, and various alternate mass spectrometry-based systems.

In a non-limiting embodiment, a high throughput screening (HTS) assay may be implemented using conventional triple-quadrupole mass spectrometry technology. The HTS assay works by directly injecting a serum extract into the triple-quad mass spectrometer, which then individually isolates each of the parent molecules by single-ion monitoring (SIM). This is followed by the fragmentation of each molecule using an inert gas, such as N₂(called a collision gas, collectively referred to as collision-induced dissociation or OD). The intensity of a specific fragment from each parent GTA biomarker is then measured and recorded, through a process called multiple-reaction monitoring (MRM). In addition, an internal standard molecule is also added to each sample and subjected to fragmentation as well. This internal standard fragment should have the same intensity in each sample if the method and instrumentation is operating correctly. When all biomarker fragment intensities, as well as the internal standard fragment intensities are collected, a ratio of the biomarker to IS fragment intensity is calculated, and the ratio log-transformed. The values for each subject sample are then compared to a previously determined distribution of disease-positive and controls, to determine the relative likelihood that the person is positive or negative for the disease state.

In further embodiments of the present invention, a test kit is provided for a subject to collect a small blood specimen, such as finger-prick dried blood spot or serum sample that can be analyzed by a central processing facility to test GTA metabolite levels as an indicator of GI inflammatory state. The central processing facility then reports the result back to the subject through one of various mechanisms, such as printed report, cloud-based electronic record, or other wireless type of communication. In the case of a positive test result (low GTA level), the subject would have the opportunity to purchase a GTA-augmenting anti-inflammatory prebiotic, probiotic, or synthetic GTA product. FIG. 2 illustrates a schematic diagram of this personalized testing and treatment approach.

A central processing facility can involve numerous options for the deployment of the GTA metabolite test assay. These may include, but are not limited to: 1, the development of MS/MS methods compatible with current laboratory instrumentation and triple-quadrupole mass spectrometers which are readily in place in several labs around the world, and/or 2, the establishment of a testing facility where samples could be shipped and analyzed at one location, and the results sent back to the patient or patient's physician.

Also described herein are therapeutic compositions comprising artificial, natural, or synthetic active agents for increasing endogenous GTA levels within the body.

Such therapeutic compositions may contain probiotic, non-pathogenic bacterial populations effective for increasing GTA levels within the body. These therapeutic compositions may also be useful for the prevention, control, and/or treatment of diseases, disorders and conditions associated with gastrointestinal (GI) inflammation and/or GI-related cancers, including but not limited to colorectal cancer, pancreatic cancer, and ovarian cancer.

In some embodiments, the therapeutic compositions contain prebiotics, e.g., carbohydrates, in conjunction with the microbial populations.

In embodiments of the foregoing methods, kits and compositions, the probiotic, non-pathogenic bacterial populations may comprise one or more bacterial species of the genus Blautia, species Faecalibacterium prausnitzii, genus Bacteroides, family Ruminococcaceae, family Lachnospiraceae, genus Coprococcus, genus Roseburia, genus Oscillospira, species Ruminococcus bromii, genus Ruminococcus, family Costridiaceae, species Dorea formicigenerans, species Bacteroides uniformis, genus Dorea, genus Streptococcus, order Clostridiales, genus Anaerostipes, genus Dialister, species Bifidobacterium adolescentis, family Coriobacteriaceae, genus Faecalibacterium, genus Sutterella, species Bacteroides ovatus, genus Parabacteroides, genus Ruminococcus, species Bacteroides faecis, species Eubacterium biforme, genus Phascolartobacterium, and/or family Enterobacteriaceae.

In further embodiments, the probiotic composition comprises a pharmaceutically acceptable excipient or carrier. In some embodiments, the pharmaceutically acceptable excipient or carrier may be suitable for administration to a mammalian subject by oral or rectal administration.

Non-limiting examples of suitable excipients and carriers include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and a coloring agent.

Non-limiting examples of suitable buffering agents include sodium citrate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, and calcium bicarbonate.

Non-limiting examples of suitable preservatives include antioxidants, such as alpha-tocopherol and ascorbate, and antimicrobials, such as parabens, chlorobutanol, and phenol.

In cases where a probiotic formulation contains anaerobic bacterial strains, the pharmaceutical formulation and excipients can be selected to prevent exposure of the bacterial strains to oxygen.

Non-limiting examples of suitable binders include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, and combinations thereof

Non-limiting examples of suitable lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.

Non-limiting examples of suitable dispersants include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.

In some embodiments, the composition comprises a disintegrant. In other embodiments, the disintegrant is a non-effervescent disintegrant. Non-limiting examples of suitable non-effervescent disintegrants include starches such as corn starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, microcrystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pecitin, and tragacanth. In another embodiment, the disintegrant is an effervescent disintegrant. Non-limiting examples of suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid.

Flavoring agents can be chosen from synthetic flavor oils and flavoring aromatics; natural oils; extracts from plants, leaves, flowers, and fruits; and combinations thereof. In some embodiments the flavoring agent is selected from cinnamon oils; oil of wintergreen; peppermint oils; clover oil; hay oil; anise oil; eucalyptus; vanilla; citrus oil such as lemon oil, orange oil, grape and grapefruit oil; and fruit essences including apple, peach, pear, strawberry, raspberry, cherry, plum, pineapple, and apricot.

Non-limiting examples of suitable sweeteners include glucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia Rebaudiana (Stevioside); chloro derivatives of sucrose such as sucralose; and sugar alcohols such as sorbitol, mannitol, sylitol, and the like. Also contemplated are hydrogenated starch hydrolysates and the synthetic sweetener 3,6-dihydro-6-methyl-1,2,3-oxathiazin-4-one-2,2-dioxide, particularly the potassium salt (acesulfame-K), and sodium and calcium salts thereof.

Non-limiting examples of suitable coloring agents include food, drug and cosmetic colors (FD&C), drug and cosmetic colors (D&C), and external drug and cosmetic colors (Ext. D&C).

The weight fraction of the excipient or combination of excipients in the formulation is usually about 99% or less, such as about 95% or less, about 90% or less, about 85% or less, about 80% or less, about 75% or less, about 70% or less, about 65% or less, about 60% or less, about 55% or less, 50% or less, about 45% or less, about 40% or less, about 35% or less, about 30% or less, about 25% or less, about 20% or less, about 15% or less, about 10% or less, about 5% or less, about 2% or less, or about 1% or less of the total weight of the composition.

The compositions disclosed herein can be formulated into a variety of forms and administered by a number of different means. The compositions can be administered orally, or rectally, in formulations containing conventionally acceptable carriers, adjuvants, and vehicles as desired. In an exemplary embodiment, the composition is administered orally.

Solid dosage forms for oral administration include capsules, tablets, caplets, pills, troches, lozenges, powders, and granules. A capsule typically comprises a core material comprising a bacterial composition and a shell wall that encapsulates the core material. In some embodiments, the core material comprises at least one of a solid, a liquid, and an emulsion. In other embodiments, the shell wall material comprises at least one of a soft gelatin, a hard gelatin, and a polymer. Suitable polymers include, but are not limited to: cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose (HPMC), methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose succinate and carboxymethylcellulose sodium; acrylic acid polymers and copolymers, such as those formed from acrylic acid, methacrylic acid, methyl acrylate, ammonio methylacrylate, ethyl acrylate, methyl methacrylate and/or ethyl methacrylate (e.g., those copolymers sold under the trade name “Eudragit”); vinyl polymers and copolymers such as polyvinyl pyrrolidone, polyvinyl acetate, polyvinylacetate phthalate, vinylacetate crotonic acid copolymer, and ethylene-vinyl acetate copolymers; and shellac (purified lac). In yet other embodiments, at least one polymer functions as taste-masking agents.

Tablets, pills, and the like can be compressed, multiply compressed, multiply layered, and/or coated. The coating can be single or multiple. In one embodiment, the coating material comprises at least one of a saccharide, a polysaccharide, and glycoproteins extracted from at least one of a plant, a fungus, and a microbe. Non-limiting examples include corn starch, wheat starch, potato starch, tapioca starch, cellulose, hemicellulose, dextrans, maltodextrin, cyclodextrins, inulins, pectin, mannans, gum arabic, locust bean gum, mesquite gum, guar gum, gum karaya, gum ghatti, tragacanth gum, funori, carrageenans, agar, alginates, chitosans, or gellan gum. In some embodiments the coating material comprises a protein. In another embodiment, the coating material comprises at least one of a fat and an oil. In other embodiments, the at least one of a fat and an oil is high temperature melting. In yet another embodiment, the at least one of a fat and an oil is hydrogenated or partially hydrogenated. In one embodiment, the at least one of a fat and an oil is derived from a plant. In other embodiments, the at least one of a fat and an oil comprises at least one of glycerides, free fatty acids, and fatty acid esters. In some embodiments, the coating material comprises at least one edible wax. The edible wax can be derived from animals, insects, or plants. Non-limiting examples include beeswax, lanolin, bayberry wax, carnauba wax, and rice bran wax. Tablets and pills can additionally be prepared with enteric coatings.

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

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

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

The microbial compositions, with or without one or more prebiotics, are generally formulated for oral or gastric administration, typically to a mammalian subject. In particular embodiments, the composition is formulated for oral administration as a solid, semi-solid, gel, or liquid form, such as in the form of a pill, tablet, capsule, or lozenge. In some embodiments, such formulations contain or are coated by an enteric coating to protect the bacteria through the stomach and small intestine, although spores are generally resistant to the stomach and small intestines. In other embodiments, the microbial compositions, with or without one or more prebiotics, may be formulated with a germinant to enhance engraftment, or efficacy. In yet other embodiments, the bacterial compositions may be co-formulated or co-administered with prebiotic substances, to enhance engraftment or efficacy. In some embodiments, bacterial compositions may be co-formulated or co-administered with prebiotic substances, to enhance engraftment or efficacy.

The present invention is further defined with reference to the following examples that are not to be construed as limiting.

EXAMPLES

1. Identification of Gut Microbes Associated with GTA Levels

Methods: High-throughput amplicon sequencing of the microbial V4 variable region of the microbial 16S rRNA gene was performed on total DNA extracted from 405 human colonic mucosa and fecal samples, using an Illumina Miseq instrument. Data from each sample was rarefied to 8,700 total sequences. Operational taxonomic units (OTUs) were filtered by percent contribution to the total, and the top 90% selected for comparison to serum GTA levels. Serum levels of 35 GTAs were determined on the same subjects by flow-injection tandem mass spectrometry. GTA levels were then aligned with OTU-level sequence data, followed by quintile analysis based on GTA level to identify statistically significant different OTUs between the highest and lowest GTA quintile.

Results: Comparison of OTUs between the lowest versus highest serum GTA quintiles across multiple GTAs revealed significant differences (p<E-4) in the relative abundances of several OTUs representing specific microbes, in particular short chain fatty acid-producing bacteria from the genus Blautia and species Faecalibacterium prausnitzii (Tables 1 through 34). A preliminary literature investigation of these microbes revealed roles in colon cancer, fatty acid metabolism and inflammation. Furthermore, we observed that 68% of the lowest GTA quintile comprised ulcerative colitis, Crohn's disease, and cancer, with only 25% healthy controls or non-GI related disease. The highest GTA quintile was comprised primarily of healthy individuals or non-GI related disease individuals, with only 2% of the individuals having Crohn's disease and cancer, and none with ulcerative colitis. These results suggest an involvement of both GTAs and specific microbes in GI-related inflammatory disorders and cancer. As far as we are aware, this is the first report connecting GTA metabolites with Blautia and Faecalibacterium prausnitzii in these processes.

Across all operational taxonomic units (OTUs; groups of organisms based on similarity of RNA sequence), the most frequently associated (p<E-4) gut microbes with GTA production (across all 34 GTAs as shown in Tables 1 through 34) belonged to genus Blautia (24%), species prausnitzii (19%), genus Bacteroides (12%), family Ruminococcaceae (7%), family Lachnospiraceae (7%). The remaining OTU categories and their percent frequencies are shown in FIG. 3.

TABLE 1

Gut microbes corresponding with high and low GTA-446 levels

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA445383

81
0.52
80
2.29
2.93E−76
−34.8

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.37
80
3.81
7.06E−06
−4.6
10.3

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v967
81
0.15
80
1.70
9.38E−06
−4.6
11.5

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5402
81
0.01
80
0.25
1.40E−05
−4.5
20.2

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.17
80
1.44
1.86E−05
−4.4
8.3

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5333
81
0.04
80
0.30
2.72E−05
−4.3
8.1

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.77
80
5.2S
3.69E−05
−4.2
6.9

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v717
81
0.41
80
2.38
3.93E−05
−4.2
5.8

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v284
81
4.04
80
0.65
5.43E−05
4.1
0.2

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.48
80
3.04
5.43E−05
−4.1
6.3

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v13337
81
0.00
80
0.18
6.10E−05
−4.1

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1068
81
0.69
80
0.05
1.09E−04
4.0
0.1

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v158
81
8.16
80
1.63
1.31E−04
3.9
0.2

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v333
81
0.74
80
5.95
1.71E−04
−3.9
8.0

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v5604
81
0.04
80
0.33
1.94E−04
−3.8
8.8

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v425
81
4.48
80
0.13
1.96E−04
3.8
0.0

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1218
81
0.20
80
1.39
1.97E−04
−3.8
7.0

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v2737
81
0.02
80
0.55
2.23E−04
−3.8
22.3

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5401
81
0.01
80
0.35
2.25E−04
−3.8
28.3

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1963
81
0.07
80
0.85
2.58E−04
−3.7
11.5

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2878
81
0.38
80
0.00
2.60E−04
3.7
0.0

g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v2169
81
0.11
80
0.64
2.81E−04
−3.7
5.7

g_Dorea

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales
v1156
81
0.10
80
1.61
3.22E−04
−3.7
16.3

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v324
81
1.01
80
4.10
3.40E−04
−3.7
4.0

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Actinobacteria; c_Coriobacteriia; o_Coriobacteriales;
v379
81
0.23
80
4.71
3.80E−04
−3.6
20.1

f_Coriobacteriaceae

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v188
81
6.64
80
1.83
3.89E−04
3.6
0.3

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Clostridiaceae
v4592
81
0.04
80
0.59
4.01E−04
−3.6
15.9

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v1384
81
0.15
80
0.84
4.07E−04
−3.6
5.7

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v323
81
0.81
80
4.16
4.81E−04
−3.6
5.1

g_Anaerostipes

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v513
81
1.93
80
0.55
4.94E−04
3.6
0.3

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v696
81
1.94
80
0.04
5.05E−04
3.6
0.0

g_[Ruminococcus]; s_gnavus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v282
81
1.59
80
5.86
5.81E−04
−3.5
3.7

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1423
81
0.15
80
1.06
5.88E−04
−3.5
7.2

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v747
81
0.15
80
2.41
6.59E−04
−3.5
16.3

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v4704
81
0.04
80
0.23
6.83E−04
−3.5
6.1

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1702
81
0.07
80
0.88
6.86E−04
−3.5
11.8

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v979
81
0.35
80
1.60
6.96E−04
−3.5
4.6

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v3283
81
0.11
80
0.59
6.96E−04
−3.5
5.3

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v1106
81
0.30
80
1.43
7.02E−04
−3.5
4.8

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v2977
81
0.33
80
0.04
7.03E−04
3.5
0.1

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v5505
81
0.06
80
0.31
7.26E−04
−3.4
5.1

g_Bacteroides

k_Bacteria; p_Bacteroidetes; ac_Bacteroidia; o_Bacteroidales;
v529
81
0.15
80
1.36
7.28E−04
−3.4
9.2

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v6
81
42.17
80
96.50
7.46E−04
−3.4
2.3

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v2461
81
0.15
80
0.68
7.93E−04
−3.4
4.6

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v782
81
1.38
80
0.29
8.34E−04
3.4
0.2

g_Coprococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v1449
81
0.09
80
0.64
8.75E−04
−3.4
7.4

f_Bacteroidaceae; g_Bacteroides; s_ovatus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v14672
81
0.15
80
0.00
8.82E−04
3.4
0.0

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1678
81
0.17
80
0.59
9.48E−04
−3.4
3.4

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v3864
81
0.01
80
0.28
9.52E−04
−3.4
22.3

TABLE 2

Gut microbes corresponding with high and low GTA-448 levels

OTUs
OTUs
N1
meanQ1
N2
meanQ5
pscore
tstatistic
ratio

GTA447385

81
0.68
81
2.61
1.1E−76
−34.9

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.15
81
1.62
7.6E−06
−4.6
10.92

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.46
81
3.65
2.7E−05
−4.3
8.00

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v158
81
7.89
81
1.74
6.0E−05
4.1
0.22

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.94
81
5.22
8.8E−05
−4.0
5.57

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2977
81
0.33
81
0.04
1.3E−04
3.9
0.11

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.68
81
3.32
1.3E−04
−3.9
4.89

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v492
81
1.74
81
0.38
1.4E−04
3.9
0.22

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v782
81
1.12
81
0.22
1.6E−04
3.9
0.20

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1423
81
0.15
81
1.19
1.7E−04
−3.8
8.00

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v396
81
2.78
81
1.01
2.8E−04
3.7
0.36

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v8216
81
0.00
81
0.19
2.9E−04
−3.7

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v7784
81
0.21
81
0.00
3.6E−04
3.6
0.00

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v13337
81
0.01
81
0.17
3.6E−04
−3.6
14.00

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v284
81
3.38
81
0.84
4.4E−04
3.6
0.25

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v2737
81
0.07
81
0.59
4.4E−04
−3.6
8.00

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v14672
81
0.19
81
0.01
4.8E−04
3.6
0.07

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v324
81
1.32
81
4.62
5.0E−04
−3.6
3.50

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v188
81
5.63
81
1.88
5.1E−04
3.5
0.33

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1702
81
0.10
81
0.90
6.2E−04
−3.5
9.13

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5333
81
0.05
81
0.25
6.4E−04
−3.5
5.00

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5401
81
0.01
81
0.31
7.6E−04
−3.4
25.00

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v967
81
0.35
81
1.54
7.9E−04
−3.4
4.46

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v1384
81
0.15
81
0.79
3.6E−04
−3.4
5.33

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2930
81
0.04
81
0.49
9.5E−04
−3.4
13.33

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v333
81
1.27
81
4.59
9.5E−04
−3.4
3.61

g_Bacteroides

TABLE 3

Gut microbes corresponding with high and low GTA-450 levels

OTUs
OTUs
N1
meanQ1
N2
meanQ5
pscore
tstatistic
ratio

GTA445405

81
2.89
80
11.66
4.85E−70
−31.4

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.16
80
1.69
2.31E−05
−4.4
10.51

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5402
81
0.01
80
0.24
2.87E−05
−4.3
19.24

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.94
80
5.04
9.32E−05
−4.0
5.37

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.48
80
3.58
1.49E−04
−3.9
7.43

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v323
81
1.19
80
5.33
1.92E−04
−3.8
4.49

g_Anaerostipes

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v284
81
4.23
80
0.99
1.95E−04
3.8
0.23

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v8216
81
0.00
80
0.18
2.03E−04
−3.8

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v158
81
7.05
80
2.15
3.24E−04
3.7
0.30

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v188
81
7.17
80
2.00
3.63E−04
3.6
0.28

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v492
81
2.44
80
0.40
4.45E−04
3.6
0.16

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v12957
81
0.16
80
0.00
4.68E−04
3.6
0.00

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1423
81
0.16
80
1.29
5.09E−04
−3.5
8.02

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2874
81
0.47
80
0.06
5.41E−04
3.5
0.13

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5333
81
0.07
80
0.30
5.62E−04
−3.5
4.05

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v333
81
1.22
80
4.81
5.97E−04
−3.5
3.94

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v1384
81
0.19
80
0.86
6.05E−04
−3.5
4.66

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.02
80
0.36
6.56E−04
−3.5
14.68

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v8885
81
0.00
80
0.15
7.55E−04
−3.4

g_Roseburia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v490
81
3.67
80
0.40
8.08E−04
3.4
0.11

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5168
81
0.02
80
0.26
8.73E−04
−3.4
10.63

g_Roseburia

TABLE 4

Gut microbes corresponding with high and low GTA-452 levels.

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA451407

81
0.92
80
3.44
4E−72
−32.49

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.15
80
1.66
8E−06
−4.62
11.22

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.51
80
3.41
2E−05
−4.38
6.74

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
81
4.83
80
0.86
2E−05
4.37
0.18

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
81
7.96
80
1.84
2E−05
4.37
0.23

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v967
81
0.15
80
1.54
4E−05
−4.25
10.38

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v158
81
8.01
80
2.06
4E−05
4.22
0.26

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2737
81
0.02
80
0.64
5E−05
−4.17
25.32

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.44
80
3.20
6E−05
−4.12
7.20

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.86
80
4.61
7E−05
−4.07
5.34

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
81
1.04
80
4.41
9E−05
−4.03
4.25

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1423
81
0.15
80
1.16
2E−04
−3.79
7.85

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v490
81
4.37
80
0.44
2E−04
3.78
0.10

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v396
81
2.93
80
1.14
3E−04
3.72
0.39

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v1998
81
0.12
80
0.96
3E−04
−3.72
7.80

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v1384
81
0.15
80
1.15
3E−04
−3.70
7.76

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v4400
81
0.30
80
0.06
3E−04
3.70
0.21

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1963
81
0.12
80
0.91
3E−04
−3.67
7.39

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v1884
81
0.47
80
0.01
3E−04
3.67
0.03

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
81
0.09
80
1.08
4E−04
−3.64
12.44

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v717
81
0.38
80
1.99
4E−04
−3.62
5.19

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2170
81
0.04
80
0.91
4E−04
−3.61
24.64

g_Ruminococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2977
81
0.41
80
0.06
5E−04
3.55
0.15

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2739
81
0.06
80
0.48
5E−04
−3.55
7.69

g_[Ruminococcus]; s_torques

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v4745
81
0.04
80
0.38
6E−04
−3.50
10.12

g_Oscillospira

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v3380
81
0.41
80
0.06
6E−04
3.50
0.15

g_Bacteroides; s_ovatus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1218
81
0.31
80
1.44
6E−04
−3.49
4.66

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v1332
81
1.54
80
0.09
7E−04
3.44
0.06

g_Bacteroides; s_uniformis

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v3094
81
0.05
80
0.58
8E−04
−3.42
11.64

g_Ruminococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v8216
81
0.01
80
0.18
8E−04
−3.41
14.17

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1459
81
0.14
80
0.88
8E−04
−3.41
6.44

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v333
81
1.01
80
4.25
8E−04
−3.41
4.20

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v513
81
2.36
80
0.79
9E−04
3.40
0.33

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v13964
81
0.15
80
0.00
9E−04
3.39
0.00

g_Bacteroides

TABLE 5

Gut microbes corresponding with high and low GTA-464 levels:

OTUs
QTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA463419

81
2.22
81
8.07
2.4E−68
−30.39

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.16
81
1.78
7.9E−06
−4.62
11.08

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
81
4.51
81
0.79
1.5E−05
4.47
0.18

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.81
81
5.21
2.7E−05
−4.32
6.39

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v967
81
0.17
81
1.59
3.2E−05
−4.28
9.21

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.44
81
3.81
3.4E−05
−4.27
8.58

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1068
81
0.79
81
0.09
4.0E−05
4.22
0.11

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5402
81
0.01
81
0.22
6.6E−05
−4.10
18.000

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.53
81
3.16
8.8E−05
−4.02
5.95

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
81
7.48
81
1.93
1.1E−04
3.97
0.26

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v490
81
4.33
81
0.42
1.9E−04
3.81
0.10

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v333
81
1.02
81
4.84
2.1E−04
−3.79
4.72

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1423
81
0.15
81
1.36
2.2E−04
−3.78
9.17

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
81
0.07
81
0.94
2.6E−04
−3.74
12.67

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v717
81
0.40
81
2.06
2.7E−04
−3.72
5.22

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v158
81
6.94
81
1.93
2.8E−04
3.71
0.28

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1691
81
0.20
81
0.65
3.0E−04
−3.69
3.31

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v6
81
41.49
81
115.75
3.1E−04
−3.68
2.79

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5168
81
0.01
81
0.27
3.8E−04
−3.63
22.00

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5401
81
0.01
81
0.33
4.0E−04
−3.62
27.00

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1938
81
0.72
81
0.11
4.2E−04
3.60
0.16

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v4745
81
0.04
81
0.38
4.4E−04
−3.59
10.33

g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
81
1.09
81
4.36
4.5E−04
−3.58
4.01

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v4201
81
0.25
81
0.01
4.8E−04
3.57
0.05

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v3024
81
0.06
81
0.36
6.7E−04
−3.47
5.80

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v13337
81
0.01
81
0.16
7.0E−04
−3.46
13.00

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.02
81
0.36
7.2E−04
−3.45
14.50

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v1384
81
0.17
81
0.83
7.6E−04
−3.43
4.79

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2737
81
0.07
81
0.57
8.1E−04
−3.42
7.67

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v494
81
0.43
81
2.88
8.3E−04
−3.41
6.66

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v597
81
0.70
81
2.00
8.8E−04
−3.39
2.84

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2874
81
0.49
81
0.09
9.4E−04
3.37
0.17

g_Faecalibacterium; s_prausnitzii

TABLE 6

Gut microbes corresponding with high and low GTA-466 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA465403

82
0.54
81
2.06
2.83E−62
−27.29

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v158
82
8.71
81
1.74
9.72E−06
4.57
0.20

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
82
0.78
81
5.88
1.14E−05
−4.53
7.53

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
82
0.48
81
3.51
1.74E−05
−4.43
7.37

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
82
0.28
81
1.86
2.32E−05
−4.36
6.65

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
82
0.43
81
4.11
2.43E−05
−4.35
9.63

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
82
4.16
81
0.80
4.36E−05
4.20
0.19

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1063
82
0.65
81
0.06
4.50E−05
4.19
0.10

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
82
1.02
81
4.49
5.34E−05
−4.15
4.39

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5333
82
0.04
81
0.28
5.47E−05
−4.15
7.76

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v396
82
3.04
81
1.04
7.07E−05
4.08
0.34

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v9422
82
0.00
81
0.22
8.76E−05
−4.02

g_Roseburia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2977
82
0.41
81
0.04
1.01E−04
3.99
0.09

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2737
82
0.02
81
0.58
1.15E−04
−3.95
23.79

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1423
82
0.23
81
1.48
1.84E−04
−3.83
6.39

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1691
82
0.21
81
0.73
2.31E−04
−3.77
3.51

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v13337
82
0.00
81
0.15
2.43E−04
−3.75

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
82
6.82
81
1.95
3.39E−04
3.66
0.29

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5168
82
0.01
81
0.27
3.45E−04
−3.66
22.27

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v967
82
0.29
81
1.51
4.01E−04
−3.62
5.15

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v360
82
1.00
81
3.77
4.06E−04
−3.61
3.77

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v942
82
0.27
81
1.48
4.13E−04
−3.61
5.52

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v425
82
4.62
81
0.48
4.19E−04
3.60
0.10

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v8216
82
0.00
81
0.17
5.11E−04
−3.55

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v8145
82
0.00
81
0.19
5.74E−04
−3.51

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
82
0.13
81
0.95
5.85E−04
−3.51
7.09

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v294
82
1.23
81
4.67
6.62E−04
−3.47
3.79

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
82
0.02
81
0.36
6.63E−04
−3.47
14.68

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1218
82
0.33
81
1.42
7.58E−04
−3.43
4.31

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales
v1156
82
0.10
81
1.49
7.68E−04
−3.43
15.31

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v4745
82
0.05
81
0.38
8.23E−04
−3.41
7.85

g_Oscillospira

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2930
82
0.04
81
0.49
8.70E−04
−3.39
13.50

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v13964
82
0.15
81
0.00
8.87E−04
3.39
0.00

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v957
82
0.33
81
1.30
8.90E−04
−3.39
3.94

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v1695
82
0.18
81
0.79
9.59E−04
−3.36
4.32

f_Porphyromonadaceae; g_Parabacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v490
82
3.93
81
0.47
9.59E−04
3.36
0.12

g_Bacteroides

TABLE 7

Gut microbes corresponding with high and low GTA-468 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistit
ratio

GTA467423

81
1.23
80
5.30
2.52E−68
−30.50

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.12
80
1.68
2.71E−06
−4.87
13.57

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v967
81
0.12
80
1.65
7.27E−06
−4.64
13.37

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
81
5.57
80
0.73
1.09E−05
4.54
0.13

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.38
80
3.73
1.18E−05
−4.52
9.73

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.70
80
5.30
2.26E−05
−4.37
7.53

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2737
81
0.01
80
0.63
2.56E−05
−4.34
50.62

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
81
0.91
80
4.51
2.64E−05
−4.33
4.94

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
81
8.79
80
1.79
2.63E−05
4.33
0.20

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.47
80
3.31
2.71E−05
−4.32
7.06

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v717
81
0.32
80
2.15
6.26E−05
−4.11
6.70

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1068
81
0.72
80
0.08
9.53E−05
4.00
0.10

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v5504
81
0.00
80
0.19
1.04E−04
−3.98

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v158
81
6.78
80
1.48
1.12E−04
3.96
0.22

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v333
81
0.72
80
4.31
1.80E−04
−3.84
6.02

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1423
81
0.14
80
1.15
1.93E−04
−3.82
8.47

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2461
81
0.11
80
0.68
2.34E−04
−3.77
6.08

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1459
81
0.14
80
0.98
2.63E−04
−3.73
7.18

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v3094
81
0.04
80
0.51
2.82E−04
−3.71
13.84

g_Ruminococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5333
81
0.05
80
0.28
2.93E−04
−3.70
5.57

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.00
80
0.34
3.21E−04
−3.68

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v1384
81
0.10
80
0.96
3.28E−04
−3.67
9.75

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v1998
81
0.07
80
0.83
3.40E−04
−3.66
11.14

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v13337
81
0.00
80
0.14
4.71E−04
−3.57

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Clostridiaceae
v4592
81
0.04
80
0.59
4.75E−04
−3.57
15.86

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v1332
81
1.58
80
0.08
4.77E−04
3.57
0.05

g_Bacteroides; s_uniformis

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
81
0.09
80
0.90
5.60E−04
−3.52
10.41

g_Coprococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v3024
81
0.04
80
0.30
5.61E−04
−3.52
8.10

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v5604
81
0.05
80
0.33
5.74E−04
−3.51
6.58

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2170
81
0.01
80
0.74
5.74E−04
−3.51
59.74

g_Ruminococcus

k_Bacteria; p_Actinobacteria; c_Coriobacteriia; o_Coriobacteriales;
v2334
81
0.10
80
0.55
6.26E−04
−3.49
5.57

f_Coriobacteriaceae; g_Collinsella; s_aerofaciens

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v323
81
1.05
80
4.85
6.45E−04
−3.48
4.62

g_Anaerostipes

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v1540
81
0.11
80
0.74
6.50E−04
−3.48
6.64

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v4745
81
0.02
80
0.35
6.63E−04
−3.47
14.17

g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v3283
81
0.07
80
0.48
6.74E−04
−3.47
6.41

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v782
81
1.37
80
0.24
6.78E−04
3.47
0.17

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5401
81
0.01
80
0.31
6.95E−04
−3.46
25.31

g_Dorea; s_formicigenerans

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v490
81
5.20
80
0.31
7.01E−04
3.46
0.06

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v513
81
2.48
80
0.75
7.65E−04
3.43
0.30

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v731
81
0.06
80
2.60
8.02E−04
−3.42
42.12

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v360
81
0.86
80
3.29
8.15E−04
−3.41
3.30

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v10047
81
0.01
80
0.18
8.16E−04
−3.41
14.17

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1963
81
0.12
80
0.84
8.42E−04
−3.40
6.78

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2977
81
0.30
80
0.03
8.63E−04
3.40
0.08

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2874
81
0.52
80
0.10
8.76E−04
3.39
0.19

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v396
81
2.47
80
0.93
9.60E−04
3.36
0.37

g_Bacteroides

TABLE 8

Gut microbes corresponding with high and low GTA-474 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA473429

83
0.51
80
1.75
4.4E−68
−30.14

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
83
0.41
80
4.11
3.1E−06
−4.83
10.04

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
83
0.80
80
5.59
1.4E−05
−4.49
7.03

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
83
0.16
80
1.31
5.1E−05
−4.16
8.38

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
83
0.63
80
3.21
7.3E−05
−4.07
5.13

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v8216
83
0.00
80
0.20
1.2E−04
−3.95

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
83
1.10
80
4.41
2.5E−04
−3.74
4.02

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v2563
83
0.05
80
0.71
4.1E−04
−3.61
14.78

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales
v1156
83
0.17
80
1.65
4.2E−04
−3.60
9.78

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
83
0.14
80
1.08
4.9E−04
−3.56
7.44

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v13337
83
0.01
80
0.16
5.3E−04
−3.54
13.49

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
83
0.02
80
0.38
5.4E−04
−3.53
15.56

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Veillonellaceae;
v8010
83
0.16
80
0.00
5.6E−04
3.52
0.00

g_Dialister

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1423
83
0.13
80
1.03
5.9E−04
−3.50
7.73

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5333
83
0.07
80
0.29
7.9E−04
−3.42
3.98

g_Blautia

TABLE 9

Gut microbes corresponding with high and low GTA-476 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistit
ratio

GTA475431

82
0.66
79
2.43
5.5E−80
−36.97

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
82
0.12
79
1.63
5.3E−06
−4.71
13.39

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
82
0.46
79
4.01
1.0E−05
−4.55
8.66

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v335
82
0.89
79
5.77
1.2E−05
−4.52
6.48

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
82
0.68
79
3.65
3.4E−05
−4.27
5.34

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
82
1.26
79
4.99
7.1E−05
−4.08
3.97

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v782
82
1.56
79
0.19
8.6E−05
4.03
0.12

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1423
82
0.15
79
1.25
1.0E−04
−3.99
8.56

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
82
4.00
79
0.94
1.9E−04
3.82
0.23

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v4393
82
0.00
79
0.20
2.6E−04
−3.74

g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
82
0.11
79
1.08
2.8E−04
−3.71
9.80

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5402
82
0.02
79
0.22
3.3E−04
−3.67
8.82

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v2563
82
0.05
79
0.82
3.7E−04
−3.64
16.87

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v957
82
0.35
79
1.76
4.1E−04
−3.61
4.98

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v492
82
2.33
79
0.42
4.3E−04
3.60
0.18

g_Coprococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v158
82
7.39
79
2.29
4.7E−04
3.57
0.31

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1391
82
0.12
79
0.96
5.6E−04
−3.52
7.89

g_Roseburia; s_faecis

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v323
82
1.44
79
5.37
5.6E−04
−3.52
3.73

g_Anaerostipes

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v1540
82
0.21
79
1.14
5.7E−04
−3.52
5.50

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v1106
82
0.50
79
1.80
6.0E−04
−3.50
3.59

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2170
82
0.05
79
0.80
6.5E−04
−3.48
16.35

g_Ruminococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1938
82
0.60
79
0.11
7.2E−04
3.45
0.19

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
82
0.02
79
0.43
7.5E−04
−3.44
17.65

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
82
6.68
79
2.09
7.9E−04
3.42
0.31

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v490
82
3.76
79
0.46
8.5E−04
3.40
0.12

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2930
82
0.04
79
0.49
9.0E−04
−3.39
13.49

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1691
82
0.18
79
0.65
9.3E−04
−3.37
3.53

g_Roseburia

TABLE 10

Gut microbes corresponding with high and low GTA-478 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA477433

81
0.57
81
2.18
1.0E−75
−34.34

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v782
81
1.30
81
0.20
3.1E−05
4.29
0.15

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.46
81
3.38
5.1E−05
−4.16
7.41

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
81
4.28
81
0.95
5.6E−05
4.14
0.22

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v492
81
1.75
81
0.38
8.5E−05
4.03
0.22

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.93
81
4.70
9.5E−05
−4.00
5.08

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
81
7.20
81
1.95
1.5E−04
3.89
0.27

g_Blautia

k_Bacteria; p_Actinobacteria; c_Actinobacteria; o_Bifidobacteriales;
v949
81
0.10
81
0.90
1.9E−04
−3.82
9.13

f_Bifidobacteriaceae; g_Bifidobacterium; s_adolescentis

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.22
81
1.46
2.2E−04
−3.78
6.56

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.72
81
3.02
2.6E−04
−3.74
4.22

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v13337
81
0.00
81
0.15
2.7E−04
−3.73

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v490
81
4.17
81
0.40
3.4E−04
3.66
0.09

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2930
81
0.00
81
0.48
3.4E−04
−3.66

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.02
81
0.38
4.7E−04
−3.57
15.50

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v8216
81
0.01
81
0.19
4.8E−04
−3.57
15.00

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v529
81
0.14
81
1.41
7.2E−04
−3.45
10.36

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
81
1.26
81
4.44
7.2E−04
−3.45
3.53

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v1884
81
0.42
81
0.01
7.3E−04
3.44
0.03

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v942
81
0.30
81
1.56
7.8E−04
−3.43
5.25

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v158
81
7.56
81
2.75
8.2E−04
3.41
0.36

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
81
0.12
81
1.01
8.4E−04
−3.40
8.20

g_Coprococcus

k_Bacteria; p_Actinobacteria; c_Coriobacteriia; o_Coriobacteriales;
v1305
81
0.11
81
1.04
8.5E−04
−3.40
9.33

f_Coriobacteriaceae; g_Collinsella; s_aerofaciens

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v396
81
2.85
81
1.22
8.8E−04
3.39
0.43

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v7546
81
0.17
81
0.01
9.0E−04
3.38
0.07

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1218
81
0.31
81
1.37
9.3E−04
−3.37
4.44

g_Blautia

TABLE 11

Gut microbes corresponding with high and low GTA-484 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA483315

82
0.21
81
1.18
1.31E−52
−22.94

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5333
82
0.04
81
0.26
1.01E−04
−3.99
7.09

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v490
82
4.33
81
0.23
1.09E−04
3.97
0.05

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
82
0.82
81
4.21
2.83E−04
−3.71
5.15

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
82
0.48
81
2.90
3.20E−04
−3.68
6.10

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
82
0.29
81
1.51
3.67E−04
−3.64
5.15

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v4393
82
0.01
81
0.25
4.39E−04
−3.59
20.25

g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
82
4.23
81
1.28
5.74E−04
3.51
0.30

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1068
82
0.96
81
0.22
6.36E−04
3.48
0.23

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v14672
82
0.15
81
0.00
3.87E−04
3.39
0.00

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2874
82
0.41
81
0.06
9.90E−04
3.35
0.15

g_Faecalibacterium; s_prausnitzii

TABLE 12

Gut microbes corresponding with high and low GTA-490 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA489445

81
0.51
80
1.92
6.7E−66
−29.26

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.22
80
1.71
2.6E−05
−4.33
7.71

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.49
80
4.10
3.1E−05
−4.29
8.30

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.72
80
3.51
6.1E−05
−4.12
4.91

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.94
80
5.51
6.9E−05
−4.09
5.88

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
81
4.09
80
0.85
1.1E−04
3.98
0.21

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v13337
81
0.01
80
0.19
1.6E−04
−3.86
15.19

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1068
81
0.70
80
0.09
2.0E−04
3.81
0.12

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales
v1156
81
0.06
80
1.61
2.2E−04
−3.78
26.12

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v9826
81
0.22
80
0.00
3.8E−04
3.63
0.00

g_Bacteroides; s_uniformis

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v3283
81
0.11
80
0.61
4.9E−04
−3.56
5.51

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
81
0.11
80
0.93
5.0E−04
−3.55
8.33

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1423
81
0.21
80
1.31
6.2E−04
−3.49
6.25

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
81
1.47
80
4.74
6.4E−04
−3.48
3.22

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.02
80
0.36
6.6E−04
−3.48
14.68

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v5505
81
0.05
80
0.29
6.8E−04
−3.47
5.82

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v158
81
7.33
80
2.26
7.0E−04
3.46
0.31

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5333
81
0.06
80
0.28
7.5E−04
−3.44
4.45

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v184
81
11.21
80
2.55
8.1E−04
3.41
0.23

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
81
6.64
80
2.10
8.4E−04
3.41
0.32

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v490
81
5.31
80
0.46
8.4E−04
3.41
0.09

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v8216
81
0.01
80
0.19
9.1E−04
−3.38
15.19

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Clostridiaceae;
v8086
81
0.00
80
0.16
9.5E−04
−3.37

g_SMB53

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v3864
81
0.01
80
0.28
9.5E−04
−3.37
22.27

TABLE 13

Gut microbes corresponding with high and low GTA-492 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA491241

81
0.02
79
0.75
1.01E−62
−27.80

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v158
81
10.64
79
1.89
3.78E−07
5.12
0.18

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.46
79
4.14
2.60E−06
−4.88
9.06

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.38
79
3.97
2.98E−06
−4.85
10.39

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v967
81
0.21
79
2.01
7.62E−06
−4.63
9.59

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.19
79
1.57
7.67E−06
−4.63
8.48

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
81
0.99
79
4.99
9.21E−06
−4.58
5.05

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v3283
81
0.05
79
0.66
9.30E−06
−4.53
13.33

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1068
81
0.83
79
0.06
1.19E−05
4.52
0.08

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
81
3.57
79
0.48
1.41E−05
4.48
0.13

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v396
81
3.42
79
1.15
1.79E−05
4.42
0.34

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.60
79
5.10
2.05E−05
−4.39
8.43

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v717
81
0.47
79
2.77
5.37E−05
−4.15
5.91

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v125
81
2.52
79
10.48
6.00E−05
−4.12
4.16

g_Oscillospira

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v2977
81
0.43
79
0.04
9.02E−05
4.02
0.09

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2169
81
0.09
79
0.65
9.11E−05
−4.02
7.47

g_Dorea

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v282
81
1.53
79
6.44
9.60E−05
−4.00
4.21

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Clostridaceae
v4592
81
0.01
79
0.61
1.19E−04
−3.95
49.22

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5333
81
0.05
79
0.30
1.28E−04
−3.93
6.15

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5401
81
0.04
79
0.41
1.75E−04
−3.84
10.94

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2737
81
0.05
79
0.58
1.92E−04
−3.82
11.79

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v1679
81
0.17
79
1.01
2.15E−04
−3.79
5.86

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1423
81
0.16
79
1.15
2.46E−04
−3.75
7.18

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v111
81
4.33
79
15.13
2.48E−04
−3.75
3.49

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1218
81
0.22
79
1.30
2.58E−04
−3.74
5.87

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales
v183
81
1.95
79
6.38
2.83E−04
−3.71
3.27

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v2002
81
0.69
79
0.19
2.86E−04
3.71
0.27

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v1106
81
0.27
79
1.72
3.53E−04
−3.65
6.34

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v2503
81
0.49
79
0.14
3.59E−04
3.65
0.28

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v3564
81
0.05
79
0.59
3.84E−04
−3.63
12.05

f_Porphyromonadaceae; g_Parabacteroides; s_distasonis

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v1998
81
0.16
79
0.95
3.85E−04
−3.63
5.92

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v952
81
0.85
79
0.23
4.29E−04
3.60
0.27

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v871
81
0.33
79
2.20
4.71E−04
−3.57
6.61

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v7569
81
0.40
79
0.00
4.72E−04
3.57
0.00

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
81
5.72
79
1.56
4.98E−04
3.56
0.27

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v425
81
3.62
79
0.14
6.21E−04
3.49
0.04

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.01
79
0.32
6.34E−04
−3.49
25.63

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v979
81
0.42
79
1.71
6.62E−04
−3.47
4.07

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v11393
81
0.00
79
0.15
6.94E−04
−3.46

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v19274
81
0.00
79
0.15
6.94E−04
−3.46

f_Rikenellaceae; g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v4067
81
0.06
79
0.42
7.59E−04
−3.43
6.77

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v360
81
1.05
79
3.23
7.64E−04
−3.43
3.08

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales;
v535
81
0.83
79
2.72
7.94E−04
−3.42
3.29

f_[Mogibacteriaceae]

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v3353
81
0.01
79
0.46
8.14E−04
−3.41
36.91

g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v12412
81
0.01
79
0.19
8.28E−04
−3.41
15.38

g_Oscillospira

k_Bacteria; p_Proteobacteria; c_Betaproteobacteria; o_Burkholderiales,
v880
81
1.53
79
0.22
8.39E−04
3.40
0.14

f_Alcaligenaceae; g_Sutterella

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v8584
81
0.01
79
0.20
8.47E−04
−3.40
16.41

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Veillonellaceae;
v479
81
0.05
79
6.11
8.56E−04
−3.40
123.81

g_Phascolarctobacterium

k_Bacteria; p_Firmicutes; c_Erysipelotrichi; o_Erysipelotrichales;
v14817
81
0.00
79
0.16
8.73E−04
−3.39

f_Erysipelotrichaceae; g_[Eubacterium]; s_biforme

k_Bacteria; p_Proteobacteria; c_Betaproteobacteria; o_Burkholderiales,
v2949
81
0.56
79
0.03
9.28E−04
3.38
0.05

f_Alcaligenaceae; g_Sutterella

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Clostridiaceae
v12858
81
0.00
79
0.20
9.30E−04
−3.37

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v333
81
1.25
79
5.86
9.58E−04
−3.37
4.70

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2461
81
0.14
79
0.63
9.59E−04
−3.37
4.66

g_Coprococcus

k_Bacteria; p_Proteobacteria; c_Betaproteobacteria; o_Burkholderiales,
v457
81
2.95
79
0.66
9.81E−04
3.36
0.22

f_Alcaligenaceae; g_Sutterella

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
81
0.14
79
0.92
9.98E−04
−3.35
6.80

g_Coprococcus

TABLE 14

Gut microbes corresponding with high and low GTA-494 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA493449

81
0.76
81
2.87
3.7E−66
−29.28

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2874
81
0.58
81
0.06
8.1E−05
4.05
0.11

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.38
81
2.91
1.1E−04
−3.97
7.61

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.70
81
4.17
1.3E−04
−3.91
5.93

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.46
81
3.21
1.3E−04
−3.91
7.03

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.16
81
1.35
1.4E−04
−3.90
8.38

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5333
81
0.05
81
0.30
1.7E−04
−3.85
6.00

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
81
4.28
81
1.05
2.0E−04
3.81
0.24

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v967
81
0.15
81
1.54
2.1E−04
−3.80
10.42

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
81
0.93
81
4.21
2.2E−04
−3.78
4.55

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v8216
81
0.00
81
0.17
2.2E−04
−3.78

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
81
7.37
81
2.14
2.8E−04
3.71
0.29

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v2563
81
0.04
81
0.65
3.8E−04
−3.63
17.67

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v14672
81
0.19
81
0.01
4.8E−04
3.57
0.07

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v717
81
0.38
81
2.27
4.9E−04
−3.56
5.94

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v5505
81
0.06
81
0.31
5.7E−04
−3.51
5.00

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v1384
81
0.15
81
0.80
6.8E−04
−3.47
5.42

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v333
81
0.90
81
4.17
7.0E−04
−3.46
4.63

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v13634
81
0.00
81
0.15
8.2E−04
−3.41

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.02
81
0.35
9.0E−04
−3.38
14.00

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2930
81
0.04
81
0.49
9.5E−04
−3.37
13.33

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v1884
81
0.37
81
0.04
9.7E−04
3.36
0.10

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v15255
81
0.12
81
0.00
9.9E−04
3.36
0.00

g_Bacteroides; s_uniformis

TABLE 15

Gut microbes corresponding with high and low GTA-502 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio
inverse

GTA501457

81
0.19
80
0.89
5.2E−55
−24.12

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales;
v8216
81
0.00
80
0.20
1.4E−04
−3.90

custom-character

#DIV/0.

f_Ruminococcaceae

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v12263
81
0.00
80
0.16
9.5E−04
−3.37

custom-character

#DIV/0.

f_Rikenellaceae; g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v4516
81
0.01
80
0.41
9.5E−04
−3.37
33.41
−0.02993

f_Rikenellaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales;
v527
81
0.43
80
3.05
3.8E−04
−3.63
7.06
−0.14167

f_Lachnospiraceae; g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales;
v806
81
1.65
80
0.65
9.1E−04
3.38
0.39
−2.54511

f_Lachnospiraceae

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales;
v2371
81
0.59
80
0.21
1.8E−04
3.83
0.36
−2.78867

f_Lachnospiraceae

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales;
v1791
81
0.90
80
0.25
3.2E−04
3.68
0.28
−3.60494

f_Lachnospiraceae; g_Dorea

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales;
v404
81
3.80
80
1.00
6.5E−04
3.48
0.26
−3.80247

f_Lachnospiraceae; g_Coprococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v4941
81
0.37
80
0.06
2.7E−04
3.73
0.17
−5.92593

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales;
v4835
81
0.41
80
0.01
8.6E−04
3.40
0.03
−32.5926

f_Lachnospiraceae; g_Coprococcus

TABLE 16

Gut microbes corresponding with high and low GTA-504 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA503459

81
0.17
80
0.77
8.4E−80
−36.87

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v3729
81
0.02
80
0.53
6.9E−05
−4.09
21.26

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v3710
81
0.04
80
0.35
1.4E−04
−3.91
9.45

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v9826
81
0.17
80
0.00
2.5E−04
3.75
0.00

g_Bacteroides; s_uniformis

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2237
81
0.63
80
0.16
2.6E−04
3.74
0.26

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.12
80
1.20
3.3E−04
−3.67
9.72

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v2034
81
0.15
80
0.89
3.5E−04
−3.65
5.99

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v7386
81
0.27
80
0.01
4.1E−04
3.61
0.05

g_Bacteroides; s_uniformis

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2930
81
0.00
80
0.48
4.4E−04
−3.59

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v47
81
11.05
80
52.38
5.0E−04
−3.55
4.74

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2874
81
0.48
80
0.06
5.0E−04
3.55
0.13

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v215
81
7.07
80
1.69
5.0E−04
3.55
0.24

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v12263
81
0.00
80
0.19
5.7E−04
−3.52

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v12
81
90.41
80
25.61
5.7E−04
3.52
0.28

g_Bacteroides; s_uniformis

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v7546
81
0.23
80
0.01
5.7E−04
3.52
0.05

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v1058
81
0.25
80
1.41
6.2E−04
−3.49
5.72

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.42
80
2.53
7.3E−04
−3.45
6.02

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v3447
81
0.44
80
0.04
8.1E−04
3.41
0.08

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v723
81
1.77
80
0.49
8.8E−04
3.39
0.23

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v8111
81
0.01
80
0.20
9.3E−04
−3.37
16.20

g_Ruminococcus; s_bromii

TABLE 17

Gut microbes corresponding with high and low GTA-512 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA511315

82
0.31
80
2.81
1.1E−50
−22.19

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v957
82
0.16
80
1.30
1.8E−05
−4.42
8.20

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
82
0.39
80
3.33
2.9E−05
−4.30
8.52

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
V1007
82
0.20
80
1.64
3.1E−05
−4.29
8.39

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v967
82
0.12
80
1.50
3.7E−05
−4.25
12.30

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
82
0.73
80
4.61
4.3E−05
−4.20
6.30

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
82
0.32
80
2.71
5.9E−05
−4.13
8.55

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v782
82
1.59
80
0.19
6.3E−05
4.11
0.12

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v188
82
9.22
80
2.58
7.1E−05
4.08
0.23

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v1540
82
0.05
80
0.85
8.1E−05
−4.05
17.42

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v284
82
5.67
80
1.34
9.2E−05
4.01
0.24

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
82
0.70
80
3.66
1.3E−04
−3.92
5.27

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v717
82
0.29
80
1.99
1.5E−04
−3.88
6.79

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v2737
82
0.01
80
0.54
2.2E−04
−3.78
44.08

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1423
82
0.13
80
1.16
2.3E−04
−3.77
8.67

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v942
82
0.26
80
1.60
2.4E−04
−3.76
6.25

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1068
82
0.93
80
0.25
3.3E−04
3.67
0.27

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v516
82
0.46
80
2.50
3.5E−04
−3.65
5.39

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v2874
82
0.50
80
0.06
3.6E−04
3.65
0.13

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v490
82
4.16
80
0.41
3.9E−04
3.62
0.10

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v10175
82
0.01
80
0.19
3.9E−04
−3.62
15.38

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v3283
82
0.05
80
0.38
3.9E−04
−3.62
7.69

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v294
82
1.18
80
5.08
4.3E−04
−3.60
4.29

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v13337
82
0.00
80
0.14
4.3E−04
−3.59

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1218
82
0.23
80
1.44
5.3E−04
−3.54
6.20

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v492
82
2.48
80
0.38
5.3E−04
3.54
0.15

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v4916
82
0.00
80
0.40
6.3E−04
−3.49

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v688
82
0.35
80
2.03
6.3E−04
−3.49
5.73

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Veillonellaceae;
v783
82
1.93
80
0.43
6.5E−04
3.48
0.22

g_Dialister

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v360
82
1.05
80
3.84
6.6E−04
−3.47
3.66

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v731
82
0.06
80
2.11
6.8E−04
−3.47
34.64

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
82
0.11
80
0.90
7.3E−04
−3.44
8.20

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v1123
82
0.21
80
1.40
7.5E−04
−3.44
6.75

f_Facalibecterium

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Veillonellaceae;
v617
82
2.13
80
0.63
7.9E−04
3.42
0.29

g_Dialister

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Veillonellaceae;
v7341
82
0.24
80
0.00
8.2E−04
3.41
0.00

g_Dialister

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellacaea;
v21051
82
0.00
80
0.13
8.5E−04
−3.40

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5168
82
0.04
80
0.29
8.5E−04
−3.40
7.86

g_Roseburia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v7465
82
0.24
80
0.04
8.8E−04
3.39
0.15

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1963
82
0.13
80
0.88
9.3E−04
−3.37
6.52

g_Blautia

TABLE 18

Gut microbes corresponding with high and low GTA-518 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA517473

82
0.17
81
0.85
1.9E−66
−29.32

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v9916
82
0.00
81
0.21
9.4E−04
−3.37

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v8216
82
0.01
81
0.20
5.0E−04
−3.56
16.20

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae
v13337
82
0.01
81
0.17
3.3E−04
−3.67
14.17

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae
v2563
82
0.06
81
0.73
4.1E−04
−3.61
11.95

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v529
82
0.21
81
1.63
6.1E−04
−3.50
7.86

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v527
82
0.50
81
3.79
2.2E−05
−4.37
7.58

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1007
82
0.21
81
1.35
2.5E−04
−3.75
6.49

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v1702
82
0.16
81
1.02
9.3E−04
−3.37
6.46

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v5333
82
0.05
81
0.28
1.6E−04
−3.87
5.82

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v407
82
0.63
81
3.60
1.8E−05
−4.43
5.68

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Lachnospiraceae;
v385
82
0.90
81
5.12
7.8E−05
−4.05
5.68

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostrida; o_Clostridiales; f_Ruminococcaceae;
v324
82
1.32
81
4.99
1.9E−04
−3.82
3.79

g_Faecalibacterium; s_prausnitzii

TABLE 19

Gut microbes corresponding with high and low GTA-520 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA519475

81
0.30
79
1.21
7.8E−74
−33.59

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.02
79
0.42
2.0E−04
−3.81
16.92

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v8216
81
0.01
79
0.18
7.4E−04
−3.44
14.35

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v2563
81
0.06
79
0.78
2.0E−04
−3.81
12.71

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.22
79
1.47
1.6E−04
−3.86
6.61

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.48
79
3.15
1.5E−04
−3.89
6.55

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1702
81
0.16
79
1.05
8.9E−04
−3.39
6.55

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.88
79
4.63
4.1E−05
−1.22
5.29

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.59
79
3.08
1.4E−04
−3.90
5.19

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v333
81
1.14
79
4.73
5.5E−04
−3.52
4.17

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5333
81
0.07
79
0.29
8.7E−04
−3.39
3.93

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v324
81
1.33
79
4.22
7.2E−04
−3.45
3.16

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v782
81
1.12
79
0.20
5.0E−04
3.56
0.18

g_Coprococcus

TABLE 20

Gut microbes corresponding with high and low GTA-522 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA521477

81
0.15
81
0.77
4.8E−70
−31.27

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Clostridiaceae
v5030
81
0.02
81
0.30
7.9E−04
−3.42
12.00

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v2563
81
0.07
81
0.65
3.3E−04
−3.67
8.83

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v10175
81
0.02
81
0.20
8.6E−04
−3.40
8.00

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.60
81
2.44
5.3E−04
−3.53
4.04

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v385
81
1.04
81
3.77
5.9E−04
−3.51
3.63

g_Blautia

TABLE 21

Gut microbes corresponding with high and low GTA-524 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA523461

83
0.06
79
0.54
3.6E−78
−35.74

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v9350
83
0.00
79
0.23
6.7E−04
−3.47

g_Ruminococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v12263
83
0.00
79
0.18
3.3E−04
−3.41

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1902
83
0.05
79
0.68
4.1E−04
−3.61
14.18

g_Ruminococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1391
83
0.08
79
0.94
5.0E−04
−3.55
11.11

g_Roseburia; s_faecis

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v2563
83
0.07
79
0.71
7.8E−04
−3.42
9.81

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v6775
83
0.02
79
0.23
9.8E−04
−3.36
9.46

g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1754
83
0.12
79
0.90
6.2E−04
−3.49
7.46

g_Ruminococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v2034
83
0.10
79
0.68
4.9E−04
−3.56
7.09

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1007
83
0.22
79
1.51
8.9E−05
−4.02
6.95

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1423
83
0.17
79
1.11
5.0E−04
−3.56
6.60

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v3710
83
0.06
79
0.33
6.0E−04
−3.50
5.46

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v527
83
0.66
79
3.27
3.0E−04
−3.70
4.93

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v385
83
1.10
79
4.82
1.4E−04
−3.90
4.40

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v333
83
1.17
79
4.38
9.0E−04
−3.38
3.75

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1286
83
0.29
79
0.97
3.0E−04
−3.69
3.37

g_Blautia

k_Bacteria; p_Firmicutes; c_Bacilli; o_Lactobacillales; f_Streptococcaceae;
v92
83
21.10
79
1.77
6.2E−04
3.49
0.08

g_Streptococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2874
83
0.48
79
0.04
1.6E−04
3.86
0.08

g_Faecalibacterium; s_prausnitzii

TABLE 22

Gut microbes corresponding with high and low GTA-530 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA523467

82
0.06
81
0.50
8.9E−87
−10.78

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v5983
82
0.00
81
0.28
8.4E−05
−1.04

g_Ruminococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v8216
82
0.00
81
0.17
5.1E−04
−3.55

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v20488
82
0.00
81
0.12
9.2E−04
−3.38

g_Ruminococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v3729
82
0.02
81
0.47
2.8E−04
−3.71
19.23

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v3710
82
0.02
81
0.36
3.7E−05
−4.24
14.68

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v5504
82
0.02
81
0.23
7.4E−04
−3.44
9.62

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v2034
82
0.09
81
0.75
1.7E−04
−3.85
8.82

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v47
82
8.85
81
48.07
4.1E−04
−3.61
5.43

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1286
82
0.30
81
1.12
2.5E−04
−3.74
3.68

g_Blautia

TABLE 23

Gut microbes corresponding with high and low GTA-532 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA531469

81
0.11
81
0.61
1.6E−81
−37.72

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v439
81
0.09
81
3.41
8.5E−04
−3.40
39.43

g_Oscillospira

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v3729
81
0.04
81
0.62
7.8E−04
−3.42
16.67

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v5983
81
0.02
81
0.27
8.2E−04
−3.41
11.00

g_Ruminococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v3710
81
0.04
81
0.36
9.3E−05
−1.01
9.67

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1819
81
0.14
81
0.72
8.8E−04
−3.39
5.27

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1286
81
0.30
81
1.07
4.8E−04
−3.56
3.63

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1791
81
0.88
81
0.28
0.1E−04
3.38
0.32

g_Dorea

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1783
81
0.65
81
0.20
7.8E−04
3.43
0.30

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v5891
81
0.23
81
0.01
5.2E−04
3.54
0.05

g_Faecalibacterium; s_prausnitzii

TABLE 24

Gut microbes corresponding with high and low GTA-536 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA535473

81
0.15
80
0.75
1.1E−73
−33.35

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.02
80
0.40
2.8E−04
−3.72
16.20

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1902
81
0.06
80
0.68
7.2E−04
−3.45
10.93

g_Ruminococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v2563
81
0.06
80
0.66
7.7E−04
−3.43
10.73

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.51
80
2.95
4.3E−04
−3.56
5.83

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v407
81
0.62
80
2.81
2.9E−04
−3.71
4.56

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.98
80
4.18
5.9E−04
−3.50
4.28

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v10464
81
0.15
80
0.00
8.8E−04
3.39
0.00

g_Bacteroides; s_uniformis

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v782
81
1.21
80
0.18
3.1E−04
3.69
0.14

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v3066
81
0.27
80
0.04
6.4E−04
3.48
0.14

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2874
81
0.37
80
0.04
8.9E−04
3.39
0.10

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v6523
81
0.27
80
0.03
9.0E−04
3.38
0.09

g_Bacteroides; s_uniformis

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v9826
81
0.17
80
0.01
9.7E−04
3.36
0.07

g_Bacteroides; s_uniformis

TABLE 25

Gut microbes corresponding with high and low GTA-538 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA537475

81
0.71
80
2.83
9.2E−61
−26.76

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v8216
81
0.00
80
0.18
2.0E−04
−3.80

custom-character

#DIV/0.

f_Ruminococcaceae

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5431
81
0.01
80
0.23
5.0E−04
−3.55
18.22

g_Roseburia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v5504
81
0.01
80
0.20
9.3E−04
−3.37
16.20

f_Rikenellaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v4916
81
0.02
80
0.38
4.3E−04
−3.60
15.19

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v2563
81
0.05
80
0.66
4.6E−04
−3.58
13.42

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5168
81
0.02
80
0.25
6.7E−04
−3.47
10.12

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v527
81
0.41
80
2.88
1.6E−04
−3.86
7.06

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v967
81
0.26
80
1.58
5.9E−04
−3.51
6.07

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v385
81
0.70
80
4.14
1.0E−04
−3.98
5.88

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1998
81
0.14
80
0.76
9.6E−04
−3.36
5.61

f_Ruminococcaceae

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v333
81
0.90
80
4.86
1.2E−04
−3.94
5.40

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v3024
81
0.07
80
0.38
8.7E−04
−3.39
5.06

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1007
81
0.25
80
1.24
7.3E−04
−3.44
5.01

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v158
81
8.31
80
2.55
8.7E−04
3.39
0.31

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v513
81
1.96
80
0.54
4.2E−04
3.60
0.27

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v188
81
7.17
80
1.70
9.5E−05
4.00
0.24

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v284
81
4.35
80
0.86
8.7E−05
4.03
0.20

g_Blautia

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v14672
81
0.17
80
0.01
9.7E−04
3.36
0.07

f_Bacteroidaceae; g_Bacteroides

TABLE 26

Gut microbes corresponding with high and low GTA-540 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA539315

82
1.36
81
7.95
2.0E−52
−22.86

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v4916
82
0.00
81
0.31
3.7E−04
−3.64

k_Bacteria; p_Proteobacteria; c_Gammaproteobacteria; o_Enterobacteriales;
v13141
82
0.00
81
0.17
5.1E−04
−3.55

f_Enterobacteriaceae

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v2737
82
0.02
81
0.49
8.2E−04
−3.41
20.25

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v5168
82
0.01
81
0.25
6.7E−04
−3.47
20.25

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v6941
82
0.01
81
0.21
9.0E−04
−3.38
17.21

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v2563
82
0.04
81
0.60
8.7E−04
−3.39
16.53

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v6547
82
0.02
81
0.36
9.6E−04
−3.36
14.68

g_Anaerostipes

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v3093
82
0.05
81
0.46
7.2E−04
−3.45
9.36

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v967
82
0.17
81
1.51
2.4E−04
−3.75
8.82

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v323
82
0.90
81
6.63
7.0E−04
−3.46
7.35

g_Anaerostipes

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v527
82
0.41
81
2.77
3.2E−04
−3.68
6.67

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v3283
82
0.06
81
0.38
9.4E−04
−3.37
6.28

g_Dorea; s_formicigenerans

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v717
82
0.41
81
2.32
4.6E−04
−3.58
5.60

g_Faecalibibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v385
82
0.74
81
4.16
2.5E−04
−3.75
5.59

g_Blautis

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1007
82
0.23
81
1.21
9.7E−04
−3.36
5.22

g_Blautis

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v333
82
0.99
81
4.32
7.4E−04
−3.44
4.37

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v1691
82
0.18
81
0.67
2.6E−04
−3.73
3.64

g_Roseburia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v12957
82
0.15
81
0.00
8.9E−04
3.39
0.00

g_Coprococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v13964
82
0.16
81
0.00
4.7E−04
3.57
0.00

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v158
82
8.95
81
3.44
6.1E−04
3.50
0.38

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v4400
82
0.29
81
0.06
7.6E−04
3.43
0.21

g_Blautis

TABLE 27

Gut microbes corresponding with high and low GTA-550 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA549487

81
0.00
81
0.43
1.1E−70
−31.61

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v439
81
0.17
81
3.57
5.4E−04
−3.53
20.64

g_Oscillospira

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v3729
81
0.02
81
0.38
8.0E−04
−3.42
15.50

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Clostridiaceae
v5030
81
0.02
81
0.27
8.2E−04
−3.41
11.00

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v2563
81
0.09
81
0.78
3.5E−04
−3.65
9.00

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v2034
81
0.10
81
0.68
9.1E−04
−3.38
6.88

g_Bacteroides

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v47
81
7.74
81
43.90
8.1E−04
−3.41
5.67

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2
81
283.12
81
133.02
5.7E−04
3.52
0.47

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1392
81
0.94
81
0.32
8.7E−04
3.39
0.34

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v723
81
1.77
81
0.54
7.8E−04
3.43
0.31

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2464
81
0.44
81
0.14
6.9E−04
3.46
0.31

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1783
81
0.69
81
0.19
3.0E−04
3.70
0.27

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2505
81
0.49
81
0.11
8.6E−04
3.40
0.22

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v2917
81
0.47
81
0.07
5.7E−04
3.52
0.16

g_Coprococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v3447
81
0.47
81
0.06
9.5E−04
3.37
0.13

g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v5762
81
0.17
81
0.01
9.0E−04
3.38
0.07

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c Bacilli; o_Lactobacillales; f_Streptococcaceae;
v8681
81
0.31
81
0.01
7.6E−04
3.43
0.04

g_Streptococcus

Table 28: Gut microbes corresponding with high and low GTA-574 levels:

TABLE 29

Gut microbes corresponding with high and low GTA-576 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA575513

82
0.08
81
0.78
1.3E−68
−30.41

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Clostridiaceae
5030
82
0.02
81
0.30
7.3E−04
−3.45
12.15

k_Bacteria; p_Firmicutes; c_Bacilli; o_Lactobacillales; f_Streptococcaceae;
11309
82
0.15
81
0.00
8.9E−04
3.39
0.00

g_Streptococcus

TABLE 30

Gut microbes corresponding with high and low GTA-580 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA579517

81
−0.05
81
0.32
2.2E−72
−32.51

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1058
81
0.25
81
1.79
2.3E−05
−4.36
7.25

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v125
81
3.83
81
12.06
8.8E−05
−4.03
3.15

g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v21
81
23.67
81
90.96
1.3E−04
−3.91
3.84

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1783
81
0.69
81
0.15
1.4E−04
3.90
0.21

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1583
81
0.25
81
0.98
1.8E−04
−3.84
3.95

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1819
81
0.21
81
1.17
1.9E−04
−3.82
5.59

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v3887
81
0.05
81
0.33
1.9E−04
−3.82
6.75

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v773
81
0.51
81
2.01
1.9E−04
−3.82
3.98

g_Ruminococcus; s_bromii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v1211
81
0.11
81
1.28
2.2E−04
−3.78
11.56

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v439
81
0.11
81
6.14
2.3E−04
−3.77
55.22

g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2
81
268.67
81
109.30
2.3E−04
3.77
0.41

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1465
81
0.89
81
0.16
2.4E−04
3.76
0.18

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v2034
81
0.06
81
0.84
2.9E−04
−3.70
13.60

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v723
81
1.67
81
0.42
3.2E−04
3.68
0.25

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1154
81
0.27
81
2.16
3.6E−04
−3.65
7.95

g_Ruminococcus; s_bromii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Rikenellaceae;
v47
81
5.67
81
54.98
4.1E−04
−3.61
9.70

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1392
81
0.86
81
0.25
4.2E−04
3.60
0.29

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2591
81
0.09
81
0.65
4.9E−04
−3.56
7.57

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v4663
81
0.05
81
0.33
5.3E−04
−3.54
6.75

g_Ruminococcus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v4509
81
0.11
81
0.51
5.9E−04
−3.51
4.56

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v7176
81
0.01
81
0.31
5.9E−04
−3.51
25.00

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2464
81
0.43
81
0.11
7.0E−04
3.46
0.26

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v545
81
0.79
81
2.80
7.1E−04
−3.45
3.55

g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v1356
81
0.93
81
0.27
8.0E−04
3.42
0.29

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v950
81
0.00
81
2.12
8.6E−04
−3.40

g_Ostillospira

TABLE 31

Gut microbes corresponding with high and low GTA-590 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA589545

83
−0.16
78
0.09
6.3E−125
−73.80

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1356
83
1.04
78
0.15
3.8E−06
4.79
0.15

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2340
83
0.59
78
0.09
7.3E−06
4.64
0.15

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v215
83
10.13
78
2.58
1.0E−05
4.56
0.25

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2
83
312.16
78
102.50
1.1E−05
4.54
0.33

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v723
83
2.57
78
0.64
1.8E−05
4.42
0.25

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2206
83
0.63
78
0.06
1.9E−05
4.41
0.10

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2558
83
0.65
78
0.06
2.0E−05
4.40
0.10

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2044
83
0.58
78
0.12
4.7E−05
4.19
0.20

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1783
83
0.78
78
0.14
5.0E−05
4.17
0.18

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1465
83
1.06
78
0.13
5.0E−05
4.17
0.12

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1791
83
0.75
78
0.15
5.8E−05
4.13
0.21

f_Lachnospiraceae; g_Dorea

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v56
83
32.48
78
9.08
6.1E−05
4.12
0.28

f_Lachnospiraceae; g_Dorea

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2874
83
0.60
78
0.08
6.8E−05
4.09
0.13

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1978
83
0.67
78
0.15
7.2E−05
4.08
0.23

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v891
83
1.42
78
0.24
7.5E−05
4.07
0.17

f_Lachnospiraceae; g_Dorea

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2282
83
0.58
78
0.13
8.0E−05
4.05
0.22

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v10462
83
0.00
78
0.17
8.0E−05
−4.05

custom-character

#DIV/0.

f_Rikenellaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1566
83
1.06
78
0.17
8.5E−05
4.04
0.16

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2157
83
0.58
78
0.12
8.5E−05
4.03
0.20

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1392
83
0.88
78
0.22
8.5E−05
4.03
0.25

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v473
83
3.33
78
0.49
1.4E−04
3.90
0.15

f_Ruminococcaceae

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v4334
83
0.33
78
0.04
1.6E−04
3.87
0.12

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v3447
83
0.55
78
0.04
1.8E−04
3.84
0.07

f_Lachnospiraceae; g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v608
83
1.72
78
0.56
1.8E−04
3.83
0.33

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1673
83
0.71
78
0.19
1.8E−04
3.83
0.27

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1549
83
0.72
78
0.19
1.8E−04
3.83
0.27

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Clostridia; o_Bacteroidales;
v1211
83
0.04
78
0.90
2.0E−04
−3.80
24.83

f_Rikenellaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v927
83
1.84
78
0.49
2.1E−04
3.80
0.26

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v3526
83
0.42
78
0.08
2.4E−04
3.76
0.18

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v3579
83
0.43
78
0.05
2.4E−04
3.76
0.12

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v567
83
2.20
78
0.47
2.4E−04
3.76
0.22

f_Lachnospiraceae; g_Dorea

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2298
83
0.39
78
0.05
2.7E−04
3.73
0.13

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v8162
83
0.25
78
0.01
2.8E−04
3.72
0.05

f_Lachnospiraceae; g_Blautia

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v6347
83
0.24
78
0.01
2.9E−04
3.71
0.05

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1377
83
0.83
78
0.24
3.3E−04
3.67
0.29

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v352
83
4.48
78
0.69
3.5E−04
3.66
0.15

f_Ruminococcaceae; g_Faecalibacterium

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1580
83
0.92
78
0.13
3.5E−04
3.65
0.14

f_Ruminococcaceae; g_Faecalibacterium

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2135
83
0.64
78
0.13
3.7E−04
3.64
0.20

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v3672
83
0.37
78
0.04
3.7E−04
3.64
0.10

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1372
83
1.13
78
0.06
3.8E−04
3.63
0.06

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2696
83
0.51
78
0.10
4.1E−04
3.61
0.20

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1822
83
0.78
78
0.22
4.2E−04
3.60
0.28

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Clostridia; o_Bacteroidales;
v3729
83
0.01
78
0.45
4.3E−04
−3.60
37.24

f_Rikenellaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2186
83
0.61
78
0.12
4.4E−04
3.59
0.19

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v364
83
0.80
78
4.01
5.0E−04
−3.55
5.05

f_Ruminococcaceae

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1812
83
0.80
78
0.23
5.0E−04
3.55
0.29

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2237
83
0.70
78
0.14
5.3E−04
3.54
0.20

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v47
83
3.63
78
44.60
5.4E−04
−3.53
12.30

f_Rikenellaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1730
83
0.76
78
0.22
5.5E−04
3.53
0.29

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v438
83
3.25
78
0.27
5.5E−04
3.52
0.08

f_Ruminococcaceae; g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v652
83
2.31
78
0.51
5.9E−04
3.51
0.22

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v556
83
2.72
78
0.35
6.2E−04
3.49
0.13

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1739
83
0.66
78
0.17
6.3E−04
3.49
0.25

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2788
83
0.51
78
0.13
6.5E−04
3.48
0.25

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v6416
83
0.24
78
0.01
7.5E−04
3.44
0.05

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v4689
83
0.29
78
0.05
7.8E−04
3.42
0.18

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2138
83
0.67
78
0.15
8.0E−04
3.42
0.23

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales;
v2013
83
0.64
78
0.17
8.1E−04
3.42
0.26

f_Bacteroidaceae; g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v13610
83
0.17
78
0.00
8.2E−04
3.41
0.00

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v439
83
0.53
78
5.06
8.7E−04
−3.39
9.55

f_Ruminococcaceae; g_Oscillospira

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales
v3796
83
0.18
78
0.00
9.2E−04
3.38
0.00

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1534
83
0.89
78
0.23
9.4E−04
3.37
0.26

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v1583
83
0.10
78
0.64
9.5E−04
−3.37
6.65

f_Ruminococcaceae; g_Ruminococcus; s_bromii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales;
v2464
83
0.45
78
0.13
9.9E−04
3.36
0.29

f_Ruminococcaceae; g_Faecalibacterium; s_prausnitzii

TABLE 32

Gut microbes corresponding with high and low GTA-592 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA591555

81
−0.02
78
0.60
1.3E−48
−21.49

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae
v364
81
0.74
78
4.49
3.5E−04
−3.66
6.06

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v2874
81
0.43
78
0.05
3.2E−04
3.41
0.12

g_Faecalibacterium; s_prausnitzii

TABLE 33

Gut microbes corresponding with high and low GTA-594 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA593557

81
0.37
81
2.08
8.1E−52
−22.67

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcaceae;
v15704
81
0.00
81
0.15
8.2E−04
−3.41

g_Faecalibacterium; s_prausnitzii

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Clostridiaceae
v5030
81
0.01
81
0.31
2.4E−04
−3.76
25.00

k_Bacteria; p_Bacteroidetes; c_Bacteroidis; o_Bacteroidales; f_Rikenellaceae;
v7275
81
0.02
81
0.22
8.7E−04
−3.39
9.00

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Ruminococcacese;
v3121
81
0.21
81
0.00
6.2E−04
3.49
0.00

g_Ruminococcus

k_Bacteria; p_Firmicutes; c_Bacilli; o_Lactobacillales; f_Streptococcacese;
v10586
81
0.20
81
0.00
6.4E−04
3.48
0.00

g_Streptococcus

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v3514
81
0.27
81
0.06
5.2E−04
3.54
0.23

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Bacilli; o_Lactobacillales; f_Streptococcaceae;
v3501
81
0.63
81
0.10
7.4E−04
3.44
0.16

g_Streptoccoccus

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae;
v4161
81
0.21
81
0.02
8.9E−04
3.39
0.12

g_Blautia

TABLE 34

Gut microbes corresponding with high and low GTA-596 levels:

OTUs
OTUs
N1
meanQ1
N2
meanQ5
p value
tstatistic
ratio

GTA595559

82
0.19
81
1.61
3.1E−34
−15.63

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Lachnospiraceae
v2563
82
0.06
81
0.56
7.1E−04
−3.45
9.11

k_Bacteria; p_Firmicutes; c_Clostridia; o_Clostridiales; f_Clostridiaceae
v5030
82
0.04
81
0.33
7.5E−04
−3.44
9.11

k_Bacteria; p_Bacteroidetes; c_Bacteroidia; o_Bacteroidales; f_Bacteroidaceae;
v2467
82
0.44
81
0.12
8.9E−04
3.39
0.28

g_Bacteroides

k_Bacteria; p_Firmicutes; c_Bacilli; o_Lactobacillales; f_Streptococcaceae;
v3501
82
0.70
81
0.10
3.2E−04
3.68
0.14

g_Streptococcus

2. Measuring GTA Levels in Gut Microbe Samples

Three human, one dog and one pig fecal samples were incubated in brain heart infusion (BHI) media under aerobic and anaerobic conditions for 24, 48, 72 and 96 hours. Cell pellets were extracted by mechanical lysis and sonication in organic solvents, followed by the analysis of the solvents by tandem mass spectrometry to determine GTA levels.

Selected GTAs were detected in most samples above background levels. For example, GTA-445.4/383.4 and GTA 447.4/385.4 were detected at relatively low levels compared to a human serum sample, but still above background levels. GTAs 449.4/405.4, 463.4/419.4, 465.4 /403.4 were all detected at levels well above background and approaching 50% of a human serum sample, particularly at 72 hours across all conditions analyzed. These results are shown in FIGS. 4-9.

The results provide the first evidence that GTAs appear to be the products of gut microbes. The present invention therefore provides for the use of microbial sources to produce GTAs or to augment GTA levels in subjects by providing probiotics containing combinations of GTA-producing microbes. This can include the commercial production of GTAs using industrial fermentation systems, methods of isolating, selecting and/or enriching for microbial strains involved in GTA production.

One or more currently preferred embodiments have been described by way of example. It will be apparent to persons skilled in the art that a number of variations and modifications can be made without departing from the scope of the invention as defined in the claims.

REFERENCES

Ben-Neriah, Y. & M. Karin (2011) Inflammation meets cancer, with NF-kappaB as the matchmaker. Nat Immunol, 12, 715-23.

Chapkin, R., D. McMurray & J. Lupton (2007) Colon cancer, fatty acids and anti-inflammatory compounds. Curr Opin Gastroenterol, 23, 48-54.

Demaria, S., E. Pikarsky, M. Karin, L. Coussens, Y. Chen, E. El-Omar, G. Trinchieri, S. Dubinett, J. Mao, E. Szabo, A. Krieg, G. Weiner, B. Fox, G. Coukos, E. Wang, R. Abraham, M. Carbone & M. Lotze (2010) Cancer and inflammation: promise for biologic therapy. J Immunother, 33, 335-351.

Freitas, R. & C. A. M. Fraga (2018) NF-kappaB-IKKbeta pathway as a target for drug development: realities, challenges and perspectives. Curr Drug Targets.

Hussain, S. P. & C. C. Harris (2007) Inflammation and cancer: an ancient link with novel potentials. Int J Cancer, 121, 2373-80.

Itzkowitz, S. & X. Yio (2004) Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol, 287, G7-17.

Maccio, A. & C. Madeddu (2012) Inflammation and ovarian cancer. Cytokine, 58, 133-47.

Marusawa, H. & B. J. Jenkins (2014) Inflammation and gastrointestinal cancer: an overview. Cancer Lett, 345, 153-6.

Ritchie, S., P. Ahiahonu, D. Jayasinghe, D. Heath, J. Liu, Y. Lu, W. Jin, A. Kavianpour, Y. Yamazaki, A. Khan, M. Hossain, K. Su-Myat, P. Wood, K. Krenitsky, I. Takemasa, M. Miyake, M. Sekimoto, M. Monden, H. Matsubara, F. Nomura & D. Goodenowe (2010a) Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection. BMC medicine, 8.

Ritchie, S., D. Heath, Y. Yamazaki, B. Grimmalt, A. Kavianpour, K. Krenitsky, H. Elshoni, I. Takemasa, M. Miyake, M. Sekimoto, M. Monden, T. Tomonaga, H. Matsubara, K. Sogawa, K. Matsushita, F. Nomura & D. Goodenowe (2010b) Reduction of novel circulating long-chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age. BMC gastroenterology, 10.

Ritchie, S. A., H. Akita, I. Takemasa, H. Eguchi, E. Pastural, H. Nagano, M. Monden, Y. Doki, M. Mori, W. Jin, T. T. Sajobi, D. Jayasinghe, B. Chitou, Y. Yamazaki, T. White & D. B. Goodenowe (2013a) Metabolic system alterations in pancreatic cancer patient serum: potential for early detection. BMC Cancer, 13, 416.

Ritchie, S. A., B. Chitou, Q. Zheng, D. Jayasinghe, W. Jin, A. Mochizuki & D. B. Goodenowe (2015) Pancreatic cancer serum biomarker PC-594: Diagnostic performance and comparison to CA19-9. World J Gastroenterol, 21, 6604-12.

Ritchie, S. A., D. Heath, Y. Yamazaki, B. Grimmalt, A. Kavianpour, K. Krenitsky, H. Elshoni, I.

Takemasa, M. Miyake, M. Sekimoto, M. Monden, T. Tomonaga, H. Matsubara, K. Sogawa, K. Matsushita, F. Nomura & D. B. Goodenowe (2010c) Reduction of novel circulating long-chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age. BMC Gastroenterol, 10, 140.

Ritchie, S. A., D. Jayasinghe, G. F. Davies, P. Ahiahonu, H. Ma & D. B. Goodenowe (2011) Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity. J Exp Clin Cancer Res, 30, 59.

Ritchie, S. A., J. Tonita, R. Alvi, D. Lehotay, H. Elshoni, S. Myat, J. McHattie & D. B. Goodenowe (2013b) Low-serum GTA-446 anti-inflammatory fatty acid levels as a new risk factor for colon cancer. Int J Cancer, 132, 355-62.

Schwartsburd, P. (2004) Age-promoted creation of a pro-cancer microenvironment by inflammation: pathogenesis of dyscoordinated feedback control. Mech Ageing Dev, 125, 581-590.

Spehlmann, M. & L. Eckmann (2009) Nuclear factor-kappa B in intestinal protection and destruction. Curr Opin Gastroenterol, 25, 92-99.

Surh, Y., K. Chun, H. Cha, S. Han, Y. Keum, K. Park & S. Lee (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res, 480-481, 243-268.

Terzic, J., S. Grivennikov, E. Karin & M. Karin (2010) Inflammation and colon cancer. Gastroenterology, 138, 2101-2114 e5.

Wu, Y., S. Antony, J. L. Meitzler & J. H. Doroshow (2014) Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer Lett, 345, 164-73.

Xu, C., G. Shen, C. Chen, C. Gelinas & A. Kong (2005) Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells. Oncogene, 24, 4486-4495.

The above listed publications are each incorporated herein by reference in their entirety.

Claims

1. A method for increasing gastric tract acid (GTA) production in a mammalian subject, comprising administering a therapeutically-effective amount of a composition comprising at least one live or attenuated culture containing a microbial species selected from the genus Blautia, species Faecalibacterium prausnitzii, genus Bacteroides, family Ruminococcaceae, family Lachnospiraceae, genus Coprococcus, genus Roseburia, genus Oscillospira, species Ruminococcus bromii, genus Ruminococcus, family Costridiaceae, species Dorea formicigenerans, species Bacteroides uniformis, genus Dorea, genus Streptococcus, order Clostridiales, genus Anaerostipes, genus Dialister, species Bifidobacterium adolescentis, family Coriobacteriaceae, genus Faecalibacterium, genus Sutterella, species Bacteroides ovatus, genus Parabacteroides, genus Ruminococcus, species Bacteroides faecis, species Eubacterium biforme, genus Phascolartobacterium, and family Enterobacteriaceae; or a prebiotic composition which increases growth and/or viability of said microbial species in the gut; wherein the composition increases the synthesis of at least one GTA dicarboxylic fatty acid metabolite in said subject.
2. The method of claim 1, wherein the method further comprises a step of measuring circulating levels of one or more GTA dicarboxylic fatty acid metabolite in a subject, and administering said composition if the levels of said one or more GTA dicarboxylic fatty acid metabolite in said subject are lower than a predetermined control level, an earlier test value for said subject, or a normal level for healthy subjects.
3. The method of claim 2, wherein the control comprises a predetermined threshold value for said at least one GTA dicarboxylic fatty acid metabolite.
4. The method of claim 1, wherein said composition comprises a live or attenuated culture of a microbial species from the genus Blautia, a live or attenuated culture of Faecalibacterium prausnitzii, or a combination thereof, within a pharmaceutically-acceptable carrier suitable for administration to the gastrointestinal tract of said subject.
5. The method of claim 1, wherein said GTA dicarboxylic fatty acid metabolite is a dicarboxylic fatty acid between 28 and 36 carbons comprised of a dimeric fatty acid structure of two shorter chains ranging between 14 and 18 carbons in length joined by a single or double bond.
6. The method of claim 1, wherein said GTA dicarboxylic fatty acid metabolite is selected from the group consisting of: GTA-446, GTA-448, GTA-450, GTA-452, GTA-464, GTA-466, GTA-468, GTA-474, GTA-476, GTA-478, GTA-484, GTA-490, GTA-492, GTA-494, GTA-502, GTA-504, GTA-512, GTA-518, GTA-520, GTA-522, GTA-524, GTA-530, GTA-532, GTA-536, GTA-538, GTA-540, GTA-550, GTA-574, GTA-576, GTA-580, GTA-590, GTA-592, GTA-594, and GTA-596.
7. The method of claim 1, wherein said GTA dicarboxylic fatty acid metabolite has an accurate neutral mass within 1 PPM Dalton mass accuracy of 446.3396 (GTA-446), 448.3553 (GTA-448), 450.3709 (GTA-450), 452.3866 (GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), 468.3814 (GTA-468), 474.3736 (GTA-474), 476.3866 GTA-476, 478.4022 (GTA-478), 484.3764 (GTA-484), 490.3658 (GTA-490), 492.3815 (GTA-492), 494.3971 (GTA-494), 502.4022 (GTA-502), 504.4195 (GTA-504), 512.4077 (GTA-512), 518.3974 (GTA-518), 520.4128 (GTA-520), 522.4284 (GTA-522), 524.4441 (GTA-524), 530.4335 (GTA-530), 532.4492 (GTA-532), 536.4077 (GTA-536), 538.4233 (GTA-538), 540.4389 (GTA-540), 550.4597 (GTA-550), 574.4597 (GTA-574), 576.4754 (GTA-576), 580.5067 (GTA-580), 590.4546 (GTA-590), 592.4703 (GTA-592), 594.4859 (GTA-594), or 596.5016 (GTA-596).
8. The method of claim 1, wherein said GTA dicarboxylic fatty acid metabolite has a molecular formula of C28H46O4 (GTA-446), C28H48O4 (GTA-448), C28H50O4 (GTA-450), C28H52O4 (GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), C28H52O(GTA-468), C30H50O4 (GTA-474), C30H52O4 GTA-476, C30H54O4 (GTA-478), C28H52O6 (GTA-484), C30H50O5 (GTA-490), C30H52O5 (GTA-492), C30H54O5 (GTA-494), C32H54O4 (GTA-502), C32H56O4 (GTA-504), C30H56O6 (GTA-512), C32H54O5 (GTA-518), C32H56O5 (GTA-520), C32H58O5 (GTA-522), C32H60O5 GTA-524, C34H58O4 (GTA-530), C34H60O4 (GTA-532), C32H56O6 (GTA-536), C32H58O6 (GTA-538), C32H60O6 (GTA-540), C34H62O5 (GTA-550), C36H62O5 (GTA-574), C36H64O5 (GTA-576), C36H68O5 (GTA-580), C36H62O6 (GTA-590), C36H64O6 (GTA-592), C36H66O6 (GTA-594), or C36H68O6 (GTA-596).
9. The method of claim 2, wherein said GTA dicarboxylic fatty acid metabolite is measured using collision induced dissociation (CID) tandem mass spectrometry and is selected from one or more of the GTA dicarboxylic fatty acid metabolites listed below: GTA-446, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 446.3396, the molecular formula of C28H46O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 445: 427, 409, 401, and 383,GTA-448, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 448.3553, the molecular formula of C28H48O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 447: 429, 411, 403, and 385,GTA-450, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 450.3709, the molecular formula of C28H50O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 449: 431, 413, 405, and 387,GTA-452, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 452.3866, the molecular formula of C28H52O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 451: 433, 407, and 389,GTA-464, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 464.3522, the molecular formula of C28H48O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 463: 445, 419, 401, and 383,GTA-466, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 466.3661, the molecular formula of C28H50O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 465: 447, 421, and 403,GTA-468, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 468.3814, having the molecular formula of C28H52O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 467: 449, 423, and 405,GTA-474, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 474.3736, having the molecular formula of C30H50O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 473: 455, 429, and 411,GTA-476, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 476.3866, having the molecular formula of C30H52O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 475: 457, 431, 439 and 413,GTA-478, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 478.4022, having the molecular formula of C30H54O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 477: 459, 433, 441 and 415,GTA-484, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 484.3764, having the molecular formula of C28H52O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 483: 465, 315, 439 483, 421, and 447,GTA-490, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 490.3658, having the molecular formula of C30H50O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 489: 445, 471, 427 and 319,GTA-492, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 492.3815, having the molecular formula of C30H52O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 491: 241, 249, 267, 473, and 447,GTA-494, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 494.3971, having the molecular formula of C30H54O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 493: 475, 215, and 449,GTA-502, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 502.4022, having the molecular formula of C32H54O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 501: 483, 457, 465 and 439,GTA-504, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 504.4195, having the molecular formula of C32H56O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 503: 485, 459, 467 and 441,GTA-512, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 512.4077, having the molecular formula of C30H56O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 511: 493, 315, and 467,GTA-518, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 518.3974, having the molecular formula of C32H54O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 517: 499, 473, 499, 481 and 445,GTA-520, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 520.4128, having the molecular formula of C32H56O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 519: 501, 457, 475, 459, 447 and 483,GTA-522, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 522.4284, having the molecular formula of C32H58O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 521: 503, 459, 477, 504, 441 and 485,GTA-524, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 524.4441, having the molecular formula of C32H60O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 523: 505, 461, 479, 506, 443 and 487,GTA-530, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 530.4335, having the molecular formula of C34H58O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 529: 467, 511 and 485,GTA-532, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 532.4492, having the molecular formula of C34H60O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 531: 513, 469, 487 and 495,GTA-536, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 536.4077, having the molecular formula of C32H56O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ion of parent [M−H] mass 535: 473,GTA-538, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 538.4233, having the molecular formula of C32H58O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 537: 519, 475, 493, 501 and 457,GTA-540, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 540.4389, having the molecular formula of C32H60O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 539: 315, 521, 495 and 477,GTA-550, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 550.4597, having the molecular formula of C34H62O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 549: 487, 531, 251, 253, 513, 469 and 506,GTA-574, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 574.4597, having the molecular formula of C36H62O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 573:295, 223, 555 and 511, GTA-576, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 576.4754, having the molecular formula of C36H64O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 575: 277, 297, 557, 513 and 495,GTA-580, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 580.5067, having the molecular formula of C36H68O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 579: 561, 543, 535, 517 and 499,GTA-590, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 590.4546, having the molecular formula of C36H62O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ion of parent [M−H] mass 589: 545,GTA-592, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 592.4703, having the molecular formula of C36H64O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 591: 555 and 113,GTA-594, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 594.4859, having the molecular formula of C36H66O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 593: 557 371, 315 and 277, andGTA-596, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 596.5016, having the molecular formula of C36H68O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 595: 279, 315, 297, 577 and 559.
10. The method of claim 1, wherein said GTA dicarboxylic fatty acid metabolite is GTA-446, having the formula C28H46O4 and the structure:
11. A method for determining gastrointestinal inflammation status within the body by measuring circulating levels of one or more GTA dicarboxylic fatty acid metabolite, wherein said GTA dicarboxylic fatty acid metabolite is a dicarboxylic fatty acid between 28 and 36 carbons comprised of a dimeric fatty acid structure of two shorter chains ranging between 14 and 18 carbons in length joined by a single or double bond, wherein if a level one or more of said GTA dicarboxylic fatty acid metabolites in said subject are lower than a predetermined control level, an earlier test value for said subject, or a normal level for healthy subjects, the subject is assessed as having or being at risk for gastrointestinal inflammation.
12. The method of claim 11, wherein said GTA dicarboxylic fatty acid metabolite is selected from the group consisting of: GTA-446, GTA-448, GTA-450, GTA-452, GTA-464, GTA-466, GTA-468, GTA-474, GTA-476, GTA-478, GTA-484, GTA-490, GTA-492, GTA-494, GTA-502, GTA-504, GTA-512, GTA-518, GTA-520, GTA-522, GTA-524, GTA-530, GTA-532, GTA-536, GTA-538, GTA-540, GTA-550, GTA-574, GTA-576, GTA-580, GTA-590, GTA-592, GTA-594, and GTA-596.
13. The method of claim 12, wherein said GTA dicarboxylic fatty acid metabolite has an accurate neutral mass within 1 PPM Dalton mass accuracy of 446.3396 (GTA-446), 448.3553 (GTA-448), 450.3709 (GTA-450), 452.3866 (GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), 468.3814 (GTA-468), 474.3736 (GTA-474), 476.3866 GTA-476, 478.4022 (GTA-478), 484.3764 (GTA-484), 490.3658 (GTA-490), 492.3815 (GTA-492), 494.3971 (GTA-494), 502.4022 (GTA-502), 504.4195 (GTA-504), 512.4077 (GTA-512), 518.3974 (GTA-518), 520.4128 (GTA-520), 522.4284 (GTA-522), 524.4441 (GTA-524), 530.4335 (GTA-530), 532.4492 (GTA-532), 536.4077 (GTA-536), 538.4233 (GTA-538), 540.4389 (GTA-540), 550.4597 (GTA-550), 574.4597 (GTA-574), 576.4754 (GTA-576), 580.5067 (GTA-580), 590.4546 (GTA-590), 592.4703 (GTA-592), 594.4859 (GTA-594), or 596.5016 (GTA-596).
14. The method of claim 12, wherein said GTA dicarboxylic fatty acid metabolite has a molecular formula of C28H46O4 (GTA-446), C28H48O4 (GTA-448), C28H50O4 (GTA-450), C28H52O4 (GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), C28H52O(GTA-468), C30H50O4 (GTA-474), C30H52O4 GTA-476, C30H54O4 (GTA-478), C28H52O6 (GTA-484), C30H50O5 (GTA-490), C30H52O5 (GTA-492), C30H54O5 (GTA-494), C32H54O4 (GTA-502), C32H56O4 (GTA-504), C30H56O6 (GTA-512), C32H54O5 (GTA-518), C32H56O5 (GTA-520), C32H58O5 (GTA-522), C32H60O5 GTA-524, C34H58O4 (GTA-530), C34H60O4 (GTA-532), C32H56O6 (GTA-536), C32H58O6 (GTA-538), C32H60O6 (GTA-540), C34H62O5 (GTA-550), C36H62O5 (GTA-574), C36H64O5 (GTA-576), C36H68O5 (GTA-580), C36H62O6 (GTA-590), C36H64O6 (GTA-592), C36H66O6 (GTA-594), or C36H68O6 (GTA-596).
15. The method of claim 11, wherein said GTA dicarboxylic fatty acid metabolite is measured using collision induced dissociation (CID) tandem mass spectrometry and is selected from one or more of the GTA dicarboxylic fatty acid metabolites listed below: GTA-446, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 446.3396, the molecular formula of C28H46O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 445: 427, 409, 401, and 383,GTA-448, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 448.3553, the molecular formula of C28H48O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 447: 429, 411, 403, and 385,GTA-450, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 450.3709, the molecular formula of C28H50O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 449: 431, 413, 405, and 387,GTA-452, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 452.3866, the molecular formula of C28H52O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 451: 433, 407, and 389,GTA-464, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 464.3522, the molecular formula of C28H48O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 463: 445, 419, 401, and 383,GTA-466, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 466.3661, the molecular formula of C28H50O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 465: 447, 421, and 403,GTA-468, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 468.3814, having the molecular formula of C28H52O, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 467: 449, 423, and 405,GTA-474, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 474.3736, having the molecular formula of C30H50O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 473: 455, 429, and 411,GTA-476, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 476.3866, having the molecular formula of C30H52O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 475: 457, 431, 439 and 413,GTA-478, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 478.4022, having the molecular formula of C30H54O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 477: 459, 433, 441 and 415,GTA-484, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 484.3764, having the molecular formula of C28H52O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 483: 465, 315, 439 483, 421, and 447,GTA-490, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 490.3658, having the molecular formula of C30H50O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 489: 445, 471, 427 and 319,GTA-492, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 492.3815, having the molecular formula of C30H52O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 491: 241, 249, 267, 473, and 447,GTA-494, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 494.3971, having the molecular formula of C30H54O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 493: 475, 215, and 449,GTA-502, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 502.4022, having the molecular formula of C32H54O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 501: 483, 457, 465 and 439,GTA-504, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 504.4195, having the molecular formula of C32H56O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 503: 485, 459, 467 and 441,GTA-512, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 512.4077, having the molecular formula of C30H56O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 511: 493, 315, and 467,GTA-518, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 518.3974, having the molecular formula of C32H54O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 517: 499, 473, 499, 481 and 445,GTA-520, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 520.4128, having the molecular formula of C32H56O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 519: 501, 457, 475, 459, 447 and 483,GTA-522, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 522.4284, having the molecular formula of C32H58O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 521: 503, 459, 477, 504, 441 and 485,GTA-524, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 524.4441, having the molecular formula of C32H60O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 523: 505, 461, 479, 506, 443 and 487,GTA-530, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 530.4335, having the molecular formula of C34H58O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 529: 467, 511 and 485,GTA-532, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 532.4492, having the molecular formula of C34H60O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 531: 513, 469, 487 and 495,GTA-536, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 536.4077, having the molecular formula of C32H56O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ion of parent [M−H] mass 535: 473,GTA-538, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 538.4233, having the molecular formula of C32H58O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 537: 519, 475, 493, 501 and 457,GTA-540, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 540.4389, having the molecular formula of C32H60O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 539: 315, 521, 495 and 477,GTA-550, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 550.4597, having the molecular formula of C34H62O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 549: 487, 531, 251, 253, 513, 469 and 506,GTA-574, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 574.4597, having the molecular formula of C36H62O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 573: 295, 223, 555 and 511,GTA-576, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 576.4754, having the molecular formula of C36H64O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 575: 277, 297, 557, 513 and 495,GTA-580, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 580.5067, having the molecular formula of C36H68O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 579: 561, 543, 535, 517 and 499,GTA-590, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 590.4546, having the molecular formula of C36H62O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ion of parent [M−H] mass 589: 545,GTA-592, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 592.4703, having the molecular formula of C36H64O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 591: 555 and 113,GTA-594, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 594.4859, having the molecular formula of C36H66O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 593: 557 371, 315 and 277, andGTA-596, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 596.5016, having the molecular formula of C36H68O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 595: 279, 315, 297, 577 and 559.
16. The method of claim 11, wherein said GTA dicarboxylic fatty acid metabolite is GTA-446, having the formula C28H46O4 and the structure:
17. A kit for detecting and treating a gastric tract acid (GTA) insufficiency in a mammalian subject, comprising: a blood specimen collection device for collecting a blood sample from said mammalian subject,packaging and instructions for submitting the blood sample to a central processing facility to test levels in said blood sample of one or more GTA dicarboxylic fatty acid metabolite, wherein said GTA dicarboxylic fatty acid metabolite is a dicarboxylic fatty acid between 28 and 36 carbons comprised of a dimeric fatty acid structure of two shorter chains ranging between 14 and 18 carbons in length joined by a single or double bond; andinstructions for obtaining the results of testing said blood sample from the central processing facility, wherein in the case of a positive test result comprising a detected low GTA level, a GTA-augmenting anti-inflammatory prebiotic, probiotic, or synthetic GTA product is provided.
18. The kit of claim 17, wherein the GTA-augmenting anti-inflammatory prebiotic, probiotic, or synthetic GTA product is a composition comprising at least one live or attenuated culture containing a microbial species selected from the genus Blautia, species Faecalibacterium prausnitzii, genus Bacteroides, family Ruminococcaceae, family Lachnospiraceae, genus Coprococcus, genus Roseburia, genus Oscillospira, species Ruminococcus bromii, genus Ruminococcus, family Costridiaceae, species Dorea formicigenerans, species Bacteroides uniformis, genus Dorea, genus Streptococcus, order Clostridiales, genus Anaerostipes, genus Dialister, species Bifidobacterium adolescentis, family Coriobacteriaceae, genus Faecalibacterium, genus Sutterella, species Bacteroides ovatus, genus Parabacteroides, genus Ruminococcus, species Bacteroides faecis, species Eubacterium biforme, genus Phascolartobacterium, and family Enterobacteriaceae; or a prebiotic composition which increases growth and/or viability of said microbial species in the gut; wherein the composition increases the synthesis of at least one GTA dicarboxylic fatty acid metabolite in said subject.
19. The kit of claim 17, wherein said composition is provided if the levels of said one or more GTA dicarboxylic fatty acid metabolite in said subject are lower than a predetermined control level, an earlier test value for said subject, or a normal level for healthy subjects.
20. The kit of claim 19, wherein the control comprises a predetermined threshold value for said at least one GTA dicarboxylic fatty acid metabolite.
21. The kit of claim 17, wherein said composition comprises a live or attenuated culture of a microbial species from the genus Blautia, a live or attenuated culture of Faecalibacterium prausnitzii, or a combination thereof, within a pharmaceutically-acceptable carrier suitable for administration to the gastrointestinal tract of said subject.
22. The kit of claim 17, wherein said GTA dicarboxylic fatty acid metabolite is selected from the group consisting of: GTA-446, GTA-448, GTA-450, GTA-452, GTA-464, GTA-466, GTA-468, GTA-474, GTA-476, GTA-478, GTA-484, GTA-490, GTA-492, GTA-494, GTA-502, GTA-504, GTA-512, GTA-518, GTA-520, GTA-522, GTA-524, GTA-530, GTA-532, GTA-536, GTA-538, GTA-540, GTA-550, GTA-574, GTA-576, GTA-580, GTA-590, GTA-592, GTA-594, and GTA-596.
23. The kit of claim 22, wherein said GTA dicarboxylic fatty acid metabolite has an accurate neutral mass within 1 PPM Dalton mass accuracy of 446.3396 (GTA-446), 448.3553 (GTA-448), 450.3709 (GTA-450), 452.3866 (GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), 468.3814 (GTA-468), 474.3736 (GTA-474), 476.3866 GTA-476, 478.4022 (GTA-478), 484.3764 (GTA-484), 490.3658 (GTA-490), 492.3815 (GTA-492), 494.3971 (GTA-494), 502.4022 (GTA-502), 504.4195 (GTA-504), 512.4077 (GTA-512), 518.3974 (GTA-518), 520.4128 (GTA-520), 522.4284 (GTA-522), 524.4441 (GTA-524), 530.4335 (GTA-530), 532.4492 (GTA-532), 536.4077 (GTA-536), 538.4233 (GTA-538), 540.4389 (GTA-540), 550.4597 (GTA-550), 574.4597 (GTA-574), 576.4754 (GTA-576), 580.5067 (GTA-580), 590.4546 (GTA-590), 592.4703 (GTA-592), 594.4859 (GTA-594), or 596.5016 (GTA-596).
24. The kit of claim 22, wherein said GTA dicarboxylic fatty acid metabolite has a molecular formula of C28H46O4 (GTA-446), C28H48O4 (GTA-448), C28H50O4 (GTA-450), C28H52O4 (GTA-452), 464.3522 (GTA-464), 466.3661 (GTA-466), C28H52O(GTA-468), C30H50O4 (GTA-474), C30H52O4 GTA-476, C30H54O4 (GTA-478), C28H52O6 (GTA-484), C30H50O5 (GTA-490), C30H52O(GTA-492), C30H54O5 (GTA-494), C32H54O4 (GTA-502), C32H56O4 (GTA-504), C30H56O6 (GTA-512), C32H54O5 (GTA-518), C32H56O5 (GTA-520), C32H58O5 (GTA-522), C32H60O5 GTA-524, C34H58O4 (GTA-530), C34H60O4 (GTA-532), C32H56O6 (GTA-536), C32H58O6 (GTA-538), C32H60O6 (GTA-540), C34H62O5 (GTA-550), C36H62O5 (GTA-574), C36H64O5 (GTA-576), C36H68O5(GTA-580), C36H62O6(GTA-590), C36H64O6 (GTA-592), C36H66O6 (GTA-594), or C36H68O6 (GTA-596).
25. The kit of claim 17, wherein said GTA dicarboxylic fatty acid metabolite is measured using collision induced dissociation (CID) tandem mass spectrometry and is selected from one or more of the GTA dicarboxylic fatty acid metabolites listed below: GTA-446, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 446.3396, the molecular formula of C28H46O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 445: 427, 409, 401, and 383,GTA-448, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 448.3553, the molecular formula of C28H48O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 447: 429, 411, 403, and 385,GTA-450, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 450.3709, the molecular formula of C28H50O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 449: 431, 413, 405, and 387,GTA-452, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 452.3866, the molecular formula of C28H52O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 451: 433, 407, and 389,GTA-464, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 464.3522, the molecular formula of C28H48O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 463: 445, 419, 401, and 383,GTA-466, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 466.3661, the molecular formula of C28H50O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 465: 447, 421, and 403,GTA-468, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 468.3814, having the molecular formula of C28H52O, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 467: 449, 423, and 405,GTA-474, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 474.3736, having the molecular formula of C30H50O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 473: 455, 429, and 411,GTA-476, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 476.3866, having the molecular formula of C30H52O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 475: 457, 431, 439 and 413,GTA-478, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 478.4022, having the molecular formula of C30H54O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 477: 459, 433, 441 and 415,GTA-484, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 484.3764, having the molecular formula of C28H52O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 483: 465, 315, 439 483, 421, and 447,GTA-490, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 490.3658, having the molecular formula of C30H50O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 489: 445, 471, 427 and 319,GTA-492, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 492.3815, having the molecular formula of C30H52O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 491: 241, 249, 267, 473, and 447,GTA-494, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 494.3971, having the molecular formula of C30H54O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 493: 475, 215, and 449,GTA-502, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 502.4022, having the molecular formula of C32H54O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 501: 483, 457, 465 and 439,GTA-504, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 504.4195, having the molecular formula of C32H56O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 503: 485, 459, 467 and 441,GTA-512, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 512.4077, having the molecular formula of C30H56O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 511: 493, 315, and 467,GTA-518, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 518.3974, having the molecular formula of C32H54O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 517: 499, 473, 499, 481 and 445,GTA-520, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 520.4128, having the molecular formula of C32H56O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 519: 501, 457, 475, 459, 447 and 483,GTA-522, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 522.4284, having the molecular formula of C32H58O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 521: 503, 459, 477, 504, 441 and 485,GTA-524, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 524.4441, having the molecular formula of C32H60O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 523: 505, 461, 479, 506, 443 and 487,GTA-530, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 530.4335, having the molecular formula of C34H58O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 529: 467, 511 and 485,GTA-532, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 532.4492, having the molecular formula of C34H60O4, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 531: 513, 469, 487 and 495,GTA-536, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 536.4077, having the molecular formula of C32H56O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ion of parent [M−H] mass 535: 473,GTA-538, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 538.4233, having the molecular formula of C32H58O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 537: 519, 475, 493, 501 and 457,GTA-540, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 540.4389, having the molecular formula of C32H60O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 539: 315, 521, 495 and 477,GTA-550, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 550.4597, having the molecular formula of C34H62O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 549: 487, 531, 251, 253, 513, 469 and 506,GTA-574, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 574.4597, having the molecular formula of C36H62O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 573: 295, 223, 555 and 511,GTA-576, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 576.4754, having the molecular formula of C36H64O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 575: 277, 297, 557, 513 and 495,GTA-580, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 580.5067, having the molecular formula of C36H68O5, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 579: 561, 543, 535, 517 and 499,GTA-590, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 590.4546, having the molecular formula of C36H62O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ion of parent [M−H] mass 589: 545,GTA-592, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 592.4703, having the molecular formula of C36H64O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 591: 555 and 113,GTA-594, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 594.4859, having the molecular formula of C36H66O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 593: 557 371, 315 and 277, andGTA-596, having an accurate neutral mass within 1 PPM Dalton mass accuracy of 596.5016, having the molecular formula of C36H68O6, and characterized by a OD MS/MS fragmentation pattern using N2 as collision gas and analyzed in atmospheric pressure chemical ionization (APCI) under negative ionization comprising daughter ions of parent [M−H] mass 595: 279, 315, 297, 577 and 559.
26. The kit of claim 17, wherein said GTA dicarboxylic fatty acid metabolite is GTA-446, having the formula C28H46O4 and the structure:
27. The kit of claim 17, wherein said gastric tract acid (GTA) insufficiency is an indicator of a gastrointestinal (GI) inflammatory state.

PCT Information

Filing Document	Filing Date	Country	Kind
PCT/CA2019/050449	4/12/2019	WO	00

Provisional Applications (1)

	Number	Date	Country
	62657500	Apr 2018	US

LONG CHAIN DICARBOXYLIC FATTY ACID (LCDFA) PRODUCING MICROBES AND USES THEREOF

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Provisional Applications (1)