Hydrogen Sulfide Producers Drive a Diarrhea-Like Phenotype and a Methane Producer Drives a Constipation-Like Phenotype in Animal Models
Bibliographic record
Abstract
We recently demonstrated that diarrhea-predominant irritable bowel syndrome (IBS-D) subjects have higher relative abundance (RA) of hydrogen sulfide (H 2 S)-producing Fusobacterium and Desulfovibrio species, and constipation-predominant IBS (IBS-C) subjects have higher RA of methanogen Methanobrevibacter smithii . In this study, we investigate the effects of increased methanogens or H 2 S producers on stool phenotypes in rat models. Adult Sprague–Dawley rats were fed high-fat diet (HFD) for 60 days to increase M. smithii levels, then gavaged for 10 days with water (controls) or methanogenesis inhibitors. To increase H 2 S producers, rats were gavaged with F. varium or D. piger . Stool consistency (stool wet weight (SWW)) and gas production were measured. 16S rRNA gene sequencing was performed on stool samples. In HFD diet-fed rats ( N = 30), stool M. smithii levels were increased ( P < 0.001) after 52 days, correlating with significantly decreased SWW ( P < 0.0001) at 59 days ( R = − 0.38, P = 0.037). Small bowel M. smithii levels decreased significantly in lovastatin lactone-treated rats ( P < 0.0006), and SWW increased (normalized) in lovastatin hydroxyacid-treated rats ( P = 0.0246), vs. controls ( N = 10/group). SWW increased significantly in D. piger -gavaged rats ( N = 16) on day 10 ( P < 0.0001), and in F. varium -gavaged rats ( N = 16) at all timepoints, vs. controls, with increased stool H 2 S production. 16S sequencing revealed stool microbiota alterations in rats gavaged with H 2 S producers, with higher relative abundance (RA) of other H 2 S producers, particularly Lachnospiraceae and Bilophila in F. varium -gavaged rats, and Sutterella in D. piger -gavaged rats. These findings suggest that increased M. smithii levels result in a constipation-like phenotype in a rat model that is partly reversible with methanogenesis inhibitors, whereas gavage with H 2 S producers D. piger or F. varium results in increased colonization with other H 2 S producers and diarrhea-like phenotypes. This supports roles for the increased RA of methanogens and H 2 S producers identified in IBS-C and IBS-D subjects, respectively, in contributing to stool phenotypes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".