Yano, Jessica M. and Yu, Kristie and Donaldson, Gregory P. and Shastri, Gauri G. and Ann, Phoebe and Ma, Liang and Nagler, Cathryn R. and Ismagilov, Rustem F. and Mazmanian, Sarkis K. and Hsiao, Elaine Y. (2015) Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell, 161 (2). pp. 264-276. ISSN 0092-8674. http://resolver.caltech.edu/CaltechAUTHORS:20150409-093248232
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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.
|Additional Information:||Copyright © 2015 Elsevier Inc. All rights reserved. Received: September 25, 2014; Revised: December 16, 2014; Accepted: February 18, 2015; Published: April 9, 2015. The authors acknowledge the assistance of Andrew Stefka and Taylor Feehley (University of Chicago) for contributing pilot serum and fecal samples, Taren Thron, Sara McBride, and Alyssa Maskell for caring for the animals, Drs. Nathan Dalleska and Jesse Allen (Caltech) for conducting pilot LC/MS experiments, Said Bogatyrev (Caltech) for helpful advice, Natasha Shelby (Caltech) for editing the manuscript, and the late Dr. Paul H. Patterson for his valuable support. This work was supported by the NIH Director’s Early Independence Award (5DP5OD017924 to E.Y.H.), Caltech Center for Environmental Microbial Interactions Award (to E.Y.H.), National Science Foundatio (NSF) Emerging Frontiers in Research and Innovation Award (EFRI-1137089 to R.F.I. and S.K.M.), National Human Genome Research Institute (NHGRI) grant (R01HG005826 to R.F.I.), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant (DK078938 to S.K.M.) and National Institute of Mental Health (NIMH) grant (MH100556 to S.K.M.), National Institute of Allergy and Infectious Diseases (NIAID) grant (AI106302 to C.R.N.), and Food Allergy Research and Education (FARE) and University of Chicago Digestive Diseases Center Core Grant (P30DK42086 to C.R.N.).|
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|Deposited By:||Joy Painter|
|Deposited On:||09 Apr 2015 17:47|
|Last Modified:||09 Apr 2015 18:38|
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