Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion

被引：335

作者：

Bhattarai, Yogesh ^{[1
]}

Williams, Brianna B. ^{[2
,3
]}

Battaglioli, Eric J. ^{[1
]}

Whitaker, Weston R. ^{[4
]}

Till, Lisa ^{[5
]}

Grover, Madhusudan ^{[1
,5
]}

Linden, David R. ^{[5
]}

Akiba, Yasutada ^{[6
,7
,8
]}

Kandimalla, Karunya K. ^{[9
]}

Zachos, Nicholas C. ^{[10
]}

Kaunitz, Jonathan D. ^{[6
,7
,8
,11
]}

Sonnenburg, Justin L. ^{[4
]}

Fischbach, Michael A. ^{[2
,3
]}

Farrugia, Gianrico ^{[1
,5
,12
]}

Kashyap, Purna C. ^{[1
,5
]}

机构：

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

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

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

[4] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94304 USA

[5] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA

[6] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA

[7] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA

[8] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA

[9] Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA

[10] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Baltimore, MD 21205 USA

[11] Univ Calif Los Angeles, Dept Surg, Sch Med, Los Angeles, CA 90095 USA

[12] Mayo Clin, Div Gastroenterol & Hepatol, Jacksonville, FL 32224 USA

来源：

CELL HOST & MICROBE | 2018年 / 23卷 / 06期

关键词：

ARYL-HYDROCARBON RECEPTOR; CHAIN FATTY-ACIDS; 5-HT4; RECEPTOR; TRYPTOPHAN-METABOLITES; INTESTINAL SECRETION; SEROTONIN; RAT; NEUROTRANSMITTER; PHYSIOLOGY; MOTILITY;

D O I：

10.1016/j.chom.2018.05.004

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Tryptamine, a tryptophan-derived monoamine similar to 5-hydroxytryptamine (5-HT), is produced by gut bacteria and is abundant in human and rodent feces. However, the physiologic effect of tryptamine in the gastrointestinal (GI) tract remains unknown. Here, we show that the biological effects of tryptamine are mediated through the 5-HT4 receptor (5-HT4R), a G-protein-coupled receptor (GPCR) uniquely expressed in the colonic epithelium. Tryptamine increases both ionic flux across the colonic epithelium and fluid secretion in colonoids from germ-free (GF) and humanized (ex-GF colonized with human stool) mice, consistent with increased intestinal secretion. The secretory effect of tryptamine is dependent on 5-HT4R activation and is blocked by 5-HT4R antagonist and absent in 5-HT4R-/- mice. GF mice colonized by Bacteroides thetaiotaomicron engineered to produce tryptamine exhibit accelerated GI transit. Our study demonstrates an aspect of host physiology under control of a bacterial metabolite that can be exploited as a therapeutic modality.

引用

页码：775 / +

页数：16

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