Serotonin Signaling in Gastrointestinal Disorders
Summary
Serotonin (5-hydroxytryptamine, 5-HT) is a key modulator of gut function, orchestrating motility, secretion and visceral sensitivity. More than 90 % of the body’s serotonin is synthesised by enterochromaffin cells in the intestinal mucosa via the enzyme tryptophan hydroxylase 1. Once released into the gut lumen and lamina propria, serotonin engages diverse 5-HT receptor subtypes on enteric neurons, smooth muscle cells and immune cells to coordinate peristalsis, fluid secretion and pain perception. The serotonin transporter (SERT) regulates extracellular 5-HT availability by recapturing the transmitter into epithelial cells and platelets. Dysregulation of this finely balanced signalling system underpins a spectrum of gastrointestinal disorders, including irritable bowel syndrome, inflammatory bowel disease and postoperative diarrhoea. Emerging evidence highlights an interplay between microbial metabolites, bile acids and serotonin biosynthesis, whereby alterations in the gut microbiota can shift tryptophan metabolism towards serotonin or indole pathways, with profound effects on intestinal homeostasis and immune modulation. Understanding these mechanisms reveals opportunities for novel therapeutic interventions, from receptor-targeted drugs to dietary modulation of microbiota-derived metabolites.
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Serotonin Signaling in Gastrointestinal Disorders publication trend
The graph below shows the total number of articles in serotonin signaling in gastrointestinal disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Enterochromaffin cells: specialised epithelial cells in the gut mucosa that synthesise and release serotonin.
Tryptophan hydroxylase 1 (Tph1): the rate-limiting enzyme in peripheral serotonin synthesis from the amino acid tryptophan.
Serotonin transporter (SERT): a membrane protein responsible for reuptake of extracellular serotonin into cells, controlling its availability.
5-HT receptors (5-hydroxytryptamine receptors): a family of G protein-coupled and ligand-gated ion channel receptors mediating serotonin’s effects on target cells.
Bile acids: cholesterol-derived metabolites secreted into the intestine that facilitate fat digestion and modulate enteroendocrine signalling.
Gut microbiota: the community of microorganisms inhabiting the gastrointestinal tract, influencing host metabolism and immune responses.
References
- Gut microbiota alteration after cholecystectomy contributes to post-cholecystectomy diarrhea via bile acids stimulating colonic serotonin. Gut Microbes (2023).
- Gut microbiota dysbiosis deteriorates immunoregulatory effects of tryptophan via colonic indole and LBP/HTR2B-mediated macrophage function. The ISME Journal: Multidisciplinary Journal of Microbial Ecology (2024).
- Regulation of gut luminal serotonin by commensal microbiota in mice. PLOS ONE (2017).
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