Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease

Yogesh Bhattarai, Si Jie, David R. Linden, Sayak Ghatak, Ruben A.T. Mars, Brianna B. Williams, Meng Pu, Justin L. Sonnenburg, Michael A. Fischbach, Gianrico Farrugia, Lei Sha, Purna C. Kashyap

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies emphasize the role of microbial metabolites in regulating gastrointestinal (GI) physiology through activation of host receptors, highlighting the potential for inter-kingdom signaling in treating GI disorders. In this study, we show that tryptamine, a tryptophan-derived bacterial metabolite, stimulates mucus release from goblet cells via activation of G-protein-coupled receptor (GPCR) 5-HT4R. Germ-free mice colonized with engineered Bacteroides thetaiotaomicron optimized to produce tryptamine (Trp D+) exhibit decreased weight loss and increased mucus release following dextran sodium sulfate treatment when compared with mice colonized with control B. thetaiotaomicron (Trp D-). Additional beneficial effects in preventing barrier disruption and lower disease activity index were seen only in female mice, highlighting sex-specific effects of the bacterial metabolite. This study demonstrates potential for the precise modulation of mucus release by microbially produced 5-HT4 GPCR agonist as a therapeutic strategy to treat inflammatory conditions of the GI tract.

Original languageEnglish (US)
Article number101798
JournaliScience
Volume23
Issue number12
DOIs
StatePublished - Dec 18 2020

Keywords

  • Microbiology
  • Rodent Gastroenterology

ASJC Scopus subject areas

  • General

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