ArticleMolecular metabolism2018
Enterochromaffin 5-HT cells - A major target for GLP-1 and gut microbial metabolites.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 3 of them syntheses that pooled it.
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The trial behind it
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Who cites it
163 citing papers in PubMed, 3 syntheses or guidelines pooled it, 246 citations in OpenAlex.
- Clinical efficacy of non-pharmacological treatment of functional constipation: a systematic review and network meta-analysis.Frontiers in cellular and infection microbiology · 2025Pooled it
- Global research trajectories in gut microbiota and functional constipation: a bibliometric and visualization study.Frontiers in microbiology · 2024Pooled it
- The Role of Bacteria and Its Derived Metabolites in Chronic Pain and Depression: Recent Findings and Research Progress.The international journal of neuropsychopharmacology · 2020Pooled it
- Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels.PLoS biology · 2021Trial
- Trial
- Wheat Protein Hydrolysate Fortified With l-Arginine Enhances Satiation Induced by the Capsaicinoid Nonivamide in Moderately Overweight Male Subjects.Molecular nutrition & food research · 2019Trial
- How lipid ingestion is sensed: the mechanisms underlying intestinal hormone secretion.Clinical science (London, England : 1979) · 2026Review
- Platelet-derived serotonin epigenetically programs macrophage alternative activation to orchestrate type 2 airway inflammation.Cellular & molecular immunology · 2026Article
- Activation of peripheral muscarinic receptors rescues depressive-like behaviors via gut-brain-axis, involving parasympathetic excitation.Acta pharmacologica Sinica · 2026Article
- Study on the therapeutic effects of the primary active ingredients in cinnamon oil for constipation-predominant irritable bowel syndrome and their regulatory effects on the 5-HT signaling pathway and gut microbiota.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Age-Related Decreases in Colonic Neurokinin A Content and Release Monitored Using Electrochemical Immunosensors.Neurogastroenterology and motility · 2026Article
- Irritable Bowel Syndrome Clinical Care Gaps and the Potential of Future Therapeutics Based on Peripheral Visceral Afferent Modulation.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2026Review
- The Endoterpenoid System: A Membrane-Based Logic Framework for Integrating Cannabinoid, Olfactory, and Lipid-Sensitive Receptor Crosstalk.Journal of neuroscience research · 2026Review
- TGR5 is essential for protecting from chronic stress-induced learning and memory impairments in mice by modulating inflammation associated with the gut-brain axis.Journal of neuroinflammation · 2026Article
- GLP-1 agonists and the gut microbiome: A bidirectional relationship.British journal of clinical pharmacology · 2026Review
- Molecular vehicles for therapeutic delivery of lactate in exercise and medicine.Sports medicine and health science · 2026Review
- Short-Chain Fatty Acids Activate Myenteric Neurons and Delay Colonic Motility via Free Fatty Acid Receptors 2 and 3 in the Mouse.Neurogastroenterology and motility · 2026Article
- Efficient control of enterochromaffin versus islet differentiation from human pluripotent stem cell-derived pancreatic progenitors.Nature communications · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Glucagon-Like Peptide-1 Targets in the Human Nodose Ganglion.The Journal of comparative neurology · 2026Article
103 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectives5-HT storing enterochromaffin (EC) cells are believed to respond to nutrient and gut microbial components, and 5-HT receptor-expressing afferent vagal neurons have been described to be the major sensors of nutrients in the GI-tract. However, the molecular mechanism through which EC cells sense nutrients and gut microbiota is still unclear. METHODS AND
resultsTPH1, the 5-HT generating enzyme, and chromogranin A, an acidic protein responsible for secretory granule storage of 5-HT, were highly enriched in FACS-purified EC cells from both small intestine and colon using a 5-HT antibody-based method. Surprisingly, EC cells from the small intestine did not express GPCR sensors for lipid and protein metabolites, such as FFAR1, GPR119, GPBAR1 (TGR5), CaSR, and GPR142, in contrast to the neighboring GLP-1 storing enteroendocrine cell. However, the GLP-1 receptor was particularly highly expressed and enriched in EC cells as judged both by qPCR and by immunohistochemistry using a receptor antibody. GLP-1 receptor agonists robustly stimulated 5-HT secretion from intestinal preparations using both HPLC and a specific amperometric method. Colonic EC cells expressed many different types of known and potential GPCR sensors of microbial metabolites including three receptors for SCFAs, i.e. FFAR2, OLF78, and OLF558 and receptors for aromatic acids, GPR35; secondary bile acids GPBAR1; and acyl-amides and lactate, GPR132.
conclusionNutrient metabolites apparently do not stimulate EC cells of the small intestine directly but through a paracrine mechanism involving GLP-1 secreted from neighboring enteroendocrine cells. In contrast, colonic EC cells are able to sense a multitude of different metabolites generated by the gut microbiota as well as gut hormones, including GLP-1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.