Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis

Lixiang Zhai, Chunhua Huang, Ziwan Ning, Yijing Zhang, Min Zhuang, Wei Yang, Xiaolei Wang, Jingjing Wang, Lu Zhang, Haitao Xiao, Ling Zhao, Pallavi Asthana, Yan Y. Lam, Chi Fung Willis Chow, Jian Dong Huang, Shuofeng Yuan, Kui Ming Chan, Chun Su Yuan, Johnson Yiu Nam Lau, Hoi Leong Xavier Wong*Zhao Xiang Bian*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

16 Citations (Scopus)

Abstract

Diarrhea-predominant irritable bowel syndrome (IBS-D), a globally prevalent functional gastrointestinal (GI) disorder, is associated with elevated serotonin that increases gut motility. While anecdotal evidence suggests that the gut microbiota contributes to serotonin biosynthesis, mechanistic insights are limited. We determined that the bacterium Ruminococcus gnavus plays a pathogenic role in IBS-D. Monocolonization of germ-free mice with R. gnavus induced IBS-D-like symptoms, including increased GI transit and colonic secretion, by stimulating the production of peripheral serotonin. R. gnavus-mediated catabolism of dietary phenylalanine and tryptophan generated phenethylamine and tryptamine that directly stimulated serotonin biosynthesis in intestinal enterochromaffin cells via a mechanism involving activation of trace amine-associated receptor 1 (TAAR1). This R. gnavus-driven increase in serotonin levels elevated GI transit and colonic secretion but was abrogated upon TAAR1 inhibition. Collectively, our study provides molecular and pathogenetic insights into how gut microbial metabolites derived from dietary essential amino acids affect serotonin-dependent control of gut motility.

Original languageEnglish
Pages (from-to)33-44.e5
Number of pages12
JournalCell Host and Microbe
Volume31
Issue number1
Early online date9 Dec 2022
DOIs
Publication statusPublished - 11 Jan 2023

Scopus Subject Areas

  • Virology
  • Parasitology
  • Microbiology

User-Defined Keywords

  • aromatic trace amines
  • colonic secretion
  • gastrointestinal motility
  • gut microbiota
  • irritable bowel syndrome
  • phenethylamine
  • serotonin
  • trace amine-associated receptor 1
  • tryptamine

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