Gut serotonin-producing cells as key targets of GLP-1 and gut microbial chemicals

High levels of the 5-HT generating enzyme TPH1 and chromogranin A were found in FACS-purified enterochromaffin cells from the small intestine and colon.

• Enterochromaffin cells in the small intestine lack receptors for lipid and protein metabolites, unlike neighboring GLP-1 storing cells.
• The GLP-1 receptor is significantly expressed in enterochromaffin cells, suggesting a role in nutrient sensing.
• GLP-1 receptor agonists effectively stimulated serotonin secretion from intestinal samples.
• Colonic enterochromaffin cells express various receptors for microbial metabolites, including those for short-chain fatty acids and bile acids.
• Nutrient metabolites may not directly stimulate small intestinal enterochromaffin cells but could act through GLP-1 produced by nearby enteroendocrine cells.

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