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Cell
Vol. 161 (2), 2015, Pages: 264–276

Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis

Jessica M. Yano , Kristie Yu , Gregory P. Donaldson , Gauri G. Shastri , Phoebe Ann , Liang Ma , Cathryn R. Nagler , Rustem F. Ismagilov , Sarkis K. Mazmanian , Elaine Y. Hsiao

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

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.

Graphical abstract

 

 
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