title: Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.
abstract: The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biological processes.
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Jessica M
authors: JM
authors: Yano
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Kristie
authors: K
authors: Yu
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Gregory P
authors: GP
authors: Donaldson
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Gauri G
authors: GG
authors: Shastri
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Phoebe
authors: P
authors: Ann
authors: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Liang
authors: L
authors: Ma
authors: Department of Pathology and Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors: Cathryn R
authors: CR
authors: Nagler
authors: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Rustem F
authors: RF
authors: Ismagilov
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Sarkis K
authors: SK
authors: Mazmanian
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: ehsiao@caltech.edu.
authors: Elaine Y
authors: EY
authors: Hsiao
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D019439:Chromaffin Cells; D005769:Gastrointestinal Motility; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D051379:Mice; D064307:Microbiota; D010802:Phylogeny; D012701:Serotonin / Q000096:biosynthesis*
chemical_list: D012701:Serotonin