Characterization of Serotonin Signaling Components in Patients with Inflammatory Bowel Disease
Bibliographic record
Abstract
BACKGROUND: Tryptophan hydroxylase (TPH)1 catalyzes the biosynthesis of serotonin (5-hydroxytrptamine; 5-HT) in enterochromaffin (EC) cells, the predominant source of gut 5-HT. Secreted 5-HT regulates various gut functions through diverse 5-HT receptor (5-HTR) families, and 5-HT transporter (5-HTT) sequesters its activity via uptake into surrounding cells. In inflammatory bowel disease (IBD) mucosal 5-HT signaling is altered, including upregulated EC cell numbers and 5-HT levels. We examined key mucosal 5-HT signaling components and blood 5-HT levels and, as part of a pilot study, investigated the association between 5-HTT gene-linked polymorphic region (5HTTLPR) and Crohn's disease (CD). METHODS: In the context of inflammation, colonic expressions of TPH1, 5-HTT and 5-HTRs were studied in CD patients (n=15) and healthy controls (HC; n=10) using quantitative polymerase chain reaction (qPCR). We also investigated 5HTTLPR in 40 CD patients and HC utilizing PCR and measured platelet-poor plasma (PPP) and plasma 5-HT concentrations. RESULTS: Compared with HC, inflammation in CD patients was associated with elevated TPH1, 5-HTR3, 5-HTR4, 5-HTR7 and downregulated 5-HTT expressions. In our second cohort of participants, significantly higher PPP and plasma 5-HT levels and higher S-genotype (L/S+S/S) than L/L genotype were observed in CD patients compared with HC. CONCLUSION: Our results suggest that augmented mucosal 5-HT signaling and specific 5-HTTLPR genotype-associated decreased efficiency in 5-HT reuptake, the latter through increased 5-HT availability, may contribute to inflammation in CD patients. These findings revealed important information on various components of 5-HT signaling in intestinal inflammation which may ultimately lead to effective strategies targeting this pathway in IBD.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".