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

doi:10.1016/j.isci.2020.101798

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

iScience. 2020 Nov 13;23(12):101798. doi: 10.1016/j.isci.2020.101798. eCollection 2020 Dec 18.

Authors

Affiliations

¹ Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
² Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
³ Department of Bioengineering and ChEM-H, Stanford University, CA 94305, USA.
⁴ Department of Microbiology and Immunology, Stanford University, Stanford, CA 94304, USA.
⁵ Department of Pharmacy, Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, 77 Pu He Road, Shenbei New District, Shenyang 110122, P.R. China.

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.

Keywords: Microbiology; Rodent Gastroenterology.

Abstract

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