Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3receptor expression via acetate production
Year: 2017
Type: article
Abstract: Serotonin [5-hydroxytryptamine (5-HT)], an important neurotransmitter and a paracrine messenger in the gastrointestinal tract, regulates intestinal secretion by its action primarily on 5-HT3and 5-HT4receptors. Recent studies highlight the role of gut microbiota in 5-HT biosynthesis. In this study, we determine whether human-derived gut microbiota affects host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age-matched Swiss Webster germ-free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice. 5-HT evoked a significantly greater increase in short-circuit current (Δ Isc) in GF compared with HM mice. Additionally, 5-HT3receptor mRNA and protein expression was significantly higher in GF compared with HM mice. Ondansetron, a 5-HT3receptor antagonist, inhibited 5-HT-evoked Δ Iscin GF mice but not in HM mice. Furthermore, a 5-HT3receptor-selective agonist, 2-methyl-5-hydroxytryptamine hydrochloride, evoked a significantly higher Δ Iscin GF compared with HM mice. Immunohistochemistry in 5-HT3A-green fluorescent protein mice localized 5-HT3receptor expression to enterochromaffin cells in addition to nerve fibers. The significant difference in 5-HT-evoked Δ Iscbetween GF and HM mice persisted in the presence of tetrodotoxin (TTX) but was lost after ondansetron application in the presence of TTX. Application of acetate (10 mM) significantly lowered 5-HT3receptor mRNA in GF mouse colonoids. We conclude that host secretory response to 5-HT may be modulated by gut microbiota regulation of 5-HT3receptor expression via acetate production. Epithelial 5-HT3receptor may function as a mediator of gut microbiota-driven change in intestinal secretion. NEW & NOTEWORTHY We found that gut microbiota alters serotonin (5-HT)-evoked intestinal secretion in a 5-HT3receptor-dependent mechanism and gut microbiota metabolite acetate alters 5-HT3receptor expression in colonoids. View this article's corresponding video summary at https://www.youtube.com/watch?v=aOMYJMuLTcw&feature=youtu.be .
Institutions: Mayo Clinic, University of Colorado Anschutz
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1692662918, MECHANISMS OF ALTERATION OF GASTROINTESTINAL MOTILITY BY GUT MICROBIOTA, G2958782402, G4345289906, G601308626, G8327299195, "Barrier function alterations in post-infectious irritable bowel syndrome", Mechanisms of alteration of gastrointestinal physiology by gut microbes, Mayo Center for Cell Signaling in Gastroenterology, Mechanisms of alteration of gastrointestinal physiology by gut microbes
OpenAlex ID: W2607428872