Integrated omics revealed the altered colonic microenvironment after inhibition of peripheral serotonin synthesis by LP533401
Bibliographic record
Abstract
Abstract Gut‐derived 5‐hydroxytryptamine (5‐HT), known as serotonin, plays a crucial role in regulating gastrointestinal functions. However, the impact of disruptions in gut‐derived 5‐HT synthesis on the early gut microbiome and intestinal microenvironment remains unclear. In this study, LP533401, an inhibitor targeting peripheral 5‐HT synthesis, was administered orally to neonatal rats starting at 4 days post‐birth. By day 11, inhibition of gut‐derived 5‐HT resulted in altered colonic morphology, characterized by increased crypt depth and reduced myenteric thickness. To investigate the mechanisms underlying these alterations, we employed a combination of metagenomics, mucosal transcriptome, and untargeted metabolomics on colonic samples. Metagenome profiling revealed an upregulation in the microbial two‐component system (ko02020) and tyrosine metabolism (ko00350), with minimal effects on taxa abundances. Transcriptome profiling analysis indicated the discriminant expression of genes enriched in pathogen infection‐responsive signaling (e.g., Salmonella and Yersinia infection) and the Wnt signaling pathway that affected stem cell proliferation. Consistent with increased crypt depth, marker genes related to cell proliferation were excessively activated. Metabolomics analysis indicated lower ascorbate level and higher succinic acid level, correlating with 5‐HT concentrations and increased crypt depth. Additionally, altered metabolic pathways (e.g., nucleotide metabolism, signal transduction, metabolism of cofactors and vitamins) suggested an impact on the colonic function. In summary, early inhibition of gut‐derived 5‐HT may unfavorably reshape the colonic microenvironment, affecting gut morphology, microbial function, stem cell proliferation, and mucosal metabolism.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".