Indigenous Bacteria From the Gut Microbiota Regulate Host Serotonin Biosynthesis

Cell. 2015 Apr 9;161(2):264-76. doi: 10.1016/j.cell.2015.02.047.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacteria / classification
  • Bacteria / metabolism*
  • Blood Platelets / metabolism
  • Chromaffin Cells
  • Gastrointestinal Motility
  • Gastrointestinal Tract / microbiology*
  • Humans
  • Mice
  • Microbiota*
  • Phylogeny
  • Serotonin / biosynthesis*

Substances

  • Serotonin