5-Hydroxytryptamine (serotonin) in the gastrointestinal tract.
Level 5 - mechanism / opinion, no new human data
Narrative review summarizing animal and mechanistic research
PubMed 23222853 · doi:10.1097/MED.0b013e32835bc703
What was done
This narrative review summarizes findings regarding the biological functions of gut 5-hydroxytryptamine (serotonin, 5-HT). The discussed evidence focuses on mechanistic insights from transgenic mouse models, specifically tryptophan hydroxylase 1 knockout (TPH1KO, lacking enterochromaffin cell 5-HT), tryptophan hydroxylase 2 knockout (TPH2KO, lacking neuronal 5-HT), and serotonin transporter knockout models.
What was found
The abstract reports no quantitative data. It notes that neuronal 5-HT appears more important for constitutive gastrointestinal transit than enteroendocrine 5-HT, though TPH2KO mice also exhibit an incomplete complement of enteric neurons, obscuring whether slowed transit results from missing serotonergic transmission or broader neuronal deficiency. Neuronal 5-HT promotes mucosal growth, maintenance, and neurogenesis. Enteroendocrine-derived 5-HT is involved in intestinal inflammation, with inflammation severity decreasing in TPH1KO mice and increasing with serotonin transporter deletion. Enteroendocrine 5-HT also acts hormonally to inhibit osteoblast proliferation and promote liver regeneration.
Why it matters
The review outlines how gut serotonin functions beyond simple peristaltic initiation, acting as a neurotransmitter, paracrine factor, growth factor, and endocrine hormone affecting intestinal motility, mucosal integrity, inflammation, and extra-intestinal organ physiology.
Limits
As a narrative review, it provides no systematic search methodology, meta-analytic synthesis, or quantitative effect sizes. The reported mechanisms rely on rodent genetic knockout models, and structural neurodevelopmental defects in TPH2KO models confound the distinction between signaling and developmental effects. Human clinical data were not reported in the abstract.
Cited by
- supports 95% of the body's serotonin is produced in the digestive tract.