Tryptophan‐synthesizing bacteria enhance colonic motility
Bibliographic record
Abstract
Abstract Background An emerging strategy to treat symptoms of gastrointestinal (GI) dysmotility utilizes the administration of isolated bacteria. However, the underlying mechanisms of action of these bacterial agents are not well established. Here, we elucidate a novel approach to promote intestinal motility by exploiting the biochemical capability of specific bacteria to produce the serotonin (5‐HT) precursor, tryptophan (Trp). Methods Mice were treated daily for 1 week by oral gavage of Bacillus (B.) subtilis (R0179), heat‐inactivated R0179, or a tryptophan synthase‐null strain of B. subtilis (1A2). Tissue levels of Trp, 5‐HT, and 5‐hydroxyindoleacetic acid (5‐HIAA) were measured and changes in motility were evaluated. Key results Mice treated with B. subtilis R0179 exhibited greater colonic tissue levels of Trp and the 5‐HT breakdown product, 5‐HIAA, compared to vehicle‐treated mice. Furthermore, B. subtilis treatment accelerated colonic motility in both healthy mice as well as in a mouse model of constipation. These effects were not observed with heat‐inactivated R0179 or the live 1A2 strain that does not express tryptophan synthase. Lastly, we found that the prokinetic effects of B. subtilis R0179 were blocked by coadministration of a 5‐HT 4 receptor (5‐HT 4 R) antagonist and were absent in 5‐HT 4 R knockout mice. Conclusions and inferences Taken together, these data demonstrate that intestinal motility can be augmented by treatment with bacteria that synthesize Trp, possibly through increased 5‐HT signaling and/or actions of Trp metabolites, and involvement of the 5‐HT 4 R. Our findings provide mechanistic insight into a transient and predictable bacterial strategy to promote GI motility.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
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 teacher head, 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".