Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut-Brain Axis

被引：106

作者：

Engevik, Melinda A. ^{[1
,5
]}

Luck, Berkley ^{[1
,5
]}

Visuthranukul, Chonnikant ^{[1
,5
,6
]}

Ihekweazu, Faith D. ^{[2
]}

Engevik, Amy C. ^{[7
]}

Shi, Zhongcheng ^{[1
,5
]}

Danhof, Heather A. ^{[3
]}

Chang-Graham, Alexandra L. ^{[3
]}

Hall, Anne ^{[1
,3
,5
]}

Endres, Bradley T. ^{[8
]}

Haidacher, Sigmund J. ^{[1
,5
]}

Horvath, Thomas D. ^{[1
,5
]}

Haag, Anthony M. ^{[1
,5
]}

Devaraj, Sridevi ^{[1
,5
]}

Garey, Kevin W. ^{[8
]}

Britton, Robert A. ^{[3
]}

Hyser, Joseph M. ^{[3
]}

Shroyer, Noah F. ^{[4
]}

Versalovic, James ^{[1
,5
]}

机构：

[1] Baylor Coll Med, Dept Pathol & Immunol, 1102 Bates Ave,Suite 830, Houston, TX 77030 USA

[2] Texas Childrens Hosp, Baylor Coll Med, Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Virol & Microbiol, Houston, TX 77030 USA

[4] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA

[5] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA

[6] Chulalongkorn Univ, Fac Med, Dept Pediat, Pediat Nutr Special Task Force Activating Res STA, Bangkok, Thailand

[7] Vanderbilt Univ, Dept Surg Sci, Med Ctr, Nashville, TN USA

[8] Univ Houston, Coll Pharm, Dept Pharm Practice & Translat Res, Houston, TX 77030 USA

来源：

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY | 2021年 / 11卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Serotonin; Serotonin Transporter; Bifidobacterium; Probiotics; Enteroids; Organoids; Enterochromaffin Cells; Free Fatty Acid Receptor (FFAR)2; Short-Chain Fatty Acids (SCFAs); CHAIN FATTY-ACIDS; IRRITABLE-BOWEL-SYNDROME; MARBLE-BURYING BEHAVIOR; ANXIETY-LIKE BEHAVIOR; HUMAN INTESTINAL ENTEROIDS; RANDOMIZED CLINICAL-TRIAL; EX-VIVO MODEL; ENTEROENDOCRINE CELLS; ENTEROPATHOGENIC INFECTION; GASTROINTESTINAL MOTILITY;

D O I：

10.1016/j.jcmgh.2020.08.002

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BACKGROUND & AIMS: The human gut microbiota can regulate production of serotonin (5-hydroxytryptamine [5-HTJ) from enterochromaffin cells. However, the mechanisms underlying microbial-induced serotonin signaling are not well understood. METHODS: Adult germ-free mice were treated with sterile media, live Bifidobacterium dentium, heat-killed B dentium, or live Bacteroides ovatus. Mouse and human enteroids were used to assess the effects of B dentium metabolites on 5-HT release from enterochromaffin cells. In vitro and in vivo short-chain fatty acids and 5-HT levels were assessed by mass spectrometry. Expression of tryptophan hydroxylase, short-chain fatty acid receptor free fatty acid receptor 2, 5-HT receptors, and the 5-HT re-uptake transporter (serotonin transporter) were assessed by quantitative polymerase chain reaction and immunostaining. RNA in situ hybridization assessed 5-HT-receptor expression in the brain, and 5-HT-receptor-dependent behavior was evaluated using the marble burying test. RESULTS: B dentium mono-associated mice showed increased fecal acetate. This finding corresponded with increased intestinal 5-HT concentrations and increased expression of 5-HT receptors 2a, 4, and serotonin transporter. These effects were absent in B ovatus-treated mice. Application of acetate and B dentium-secreted products stimulated 5-HT release in mouse and human enteroids. In situ hybridization of brain tissue also showed significantly increased hippocampal expression of 5-HT-receptor 2a in B dentium-treated mice relative to germfree controls. Functionally, B dentium colonization normalized species-typical repetitive and anxiety-like behaviors previously shown to be linked to 5-HT-receptor 2a. CONCLUSIONS: These data suggest that B dentium, and the bacterial metabolite acetate, are capable of regulating key components of the serotonergic system in multiple host tissues, and are associated with a functional change in adult behavior.

引用

页码：221 / 248

页数：28

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