Hydrogen sulfide produced by the gut microbiota impairs host metabolism via reducing GLP-1 levels in male mice

被引：10

作者：

Qi, Qingqing ^{[1
]}

Zhang, Huijie ^{[1
]}

Jin, Zheyu ^{[1
]}

Wang, Changchun ^{[1
]}

Xia, Mengyu ^{[1
]}

Chen, Bandy ^{[2
]}

Lv, Bomin ^{[1
,3
]}

Diaz, Ludmila Peres ^{[4
]}

Li, Xue ^{[1
]}

Feng, Ru ^{[5
]}

Qiu, Mengdi ^{[1
]}

Li, Yang ^{[6
,7
]}

Meseguer, David ^{[2
]}

Zheng, Xiaojiao ^{[6
,7
]}

Wang, Wei ^{[1
]}

Song, Wei ^{[8
]}

Huang, He ^{[9
]}

Wu, Hao ^{[1
,3
]}

Chen, Lei ^{[5
]}

Schneeberger, Marc ^{[2
]}

Yu, Xiaofei ^{[1
,10
]}

机构：

[1] Fudan Univ, Fudan Microbiome Ctr, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China

[2] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA

[3] Fudan Univ, Human Phenome Inst, Shanghai, Peoples R China

[4] Yale Univ, Sch Med, Inst Biomol Design & Discovery, Dept Immunobiol, New Haven, CT USA

[5] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai, Peoples R China

[6] Shanghai Jiao Tong Univ, Ctr Translat Med, Shanghai Peoples Hosp 6, Sch Med, Shanghai, Peoples R China

[7] Shanghai Jiao Tong Univ, Shanghai Key Lab Diabet Mellitus, Shanghai Peoples Hosp 6, Sch Med, Shanghai, Peoples R China

[8] Wuhan Univ, Zhongnan Hosp, Med Res Inst, Frontier Sci Ctr Immunol & Metab,Dept Hepatobiliar, Wuhan, Peoples R China

[9] Fudan Univ, Inst Metab & Integrat Biol, Shanghai Key Lab Metab Remodeling & Hlth, Shanghai, Peoples R China

[10] Fudan Univ, Shanghai Engn Res Ctr Ind Microorganisms, Shanghai, Peoples R China

来源：

NATURE METABOLISM | 2024年 / 6卷 / 08期

基金：

中国国家自然科学基金;

关键词：

SULFATE REDUCTION; EXPRESSION; BACTERIA; ANTIGEN;

D O I：

10.1038/s42255-024-01068-x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Dysbiosis of the gut microbiota has been implicated in the pathogenesis of metabolic syndrome (MetS) and may impair host metabolism through harmful metabolites. Here, we show that Desulfovibrio, an intestinal symbiont enriched in patients with MetS, suppresses the production of the gut hormone glucagon-like peptide 1 (GLP-1) through the production of hydrogen sulfide (H2S) in male mice. Desulfovibrio-derived H2S is found to inhibit mitochondrial respiration and induce the unfolded protein response in intestinal L cells, thereby hindering GLP-1 secretion and gene expression. Remarkably, blocking Desulfovibrio and H2S with an over-the-counter drug, bismuth subsalicylate, improves GLP-1 production and ameliorates diet-induced metabolic disorder in male mice. Together, our study uncovers that Desulfovibrio-derived H2S compromises GLP-1 production, shedding light on the gut-relayed mechanisms by which harmful microbiota-derived metabolites impair host metabolism in MetS and suggesting new possibilities for treating MetS. The intestinal symbiont Desulfovibrio, which is enriched in individuals with metabolic syndrome, is found to suppress the production of GLP-1 in male mice. The over-the-counter drug bismuth subsalicylate inhibits the effect of Desulfovibrio and restores GLP-1 levels.

引用

页码：1601 / 1615

页数：30