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

被引：47

作者：

Bhattarai, Yogesh ^{[1
]}

Jie, Si ^{[1
]}

Linden, David R. ^{[2
]}

Ghatak, Sayak ^{[1
]}

Mars, Ruben A. T. ^{[1
]}

Williams, Brianna B. ^{[3
,4
]}

Pu, Meng ^{[1
]}

Sonnenburg, Justin L. ^{[5
]}

Fischbach, Michael A. ^{[3
,4
]}

Farrugia, Gianrico ^{[1
,2
]}

Sha, Lei ^{[6
]}

Kashyap, Purna C. ^{[1
,2
]}

机构：

[1] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Physiol & Biomed Engn, 200 First St SW, Rochester, MN 55905 USA

[3] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[4] Stanford Univ, ChEM H, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94304 USA

[6] China Med Univ, Sch Pharm, Dept Pharm, Dept Neuroendocrine Pharmacol, 77 Pu He Rd, Shenyang 110122, Peoples R China

来源：

ISCIENCE | 2020年 / 23卷 / 12期

关键词：

BARRIER; DECARBOXYLASES; PERMEABILITY; EXPRESSION; STRESS;

D O I：

10.1016/j.isci.2020.101798

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：25

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