2. Academic Validation
  3. Hydrogen sulfide produced by the gut microbiota impairs host metabolism via reducing GLP-1 levels in male mice

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

  • Nat Metab. 2024 Jul 19. doi: 10.1038/s42255-024-01068-x.
Qingqing Qi # 1,  Huijie Zhang # 1,  Zheyu Jin # 1,  Changchun Wang 1,  Mengyu Xia 1,  Bandy Chen 2,  Bomin Lv 1 3,  Ludmila Peres Diaz 4,  Xue Li 1,  Ru Feng 5,  Mengdi Qiu 1,  Yang Li 6,  David Meseguer 2,  Xiaojiao Zheng 6,  Wei Wang 1,  Wei Song 7,  He Huang 8,  Hao Wu 1 3,  Lei Chen 9,  Marc Schneeberger 10,  Xiaofei Yu 11 12
Affiliations

Affiliations

  • 1 State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China.
  • 2 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
  • 3 Human Phenome Institute, Fudan University, Shanghai, China.
  • 4 Department of Immunobiology, Institute for Biomolecular Design and Discovery, Yale University School of Medicine, New Haven, CT, USA.
  • 5 Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 7 Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China.
  • 8 Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
  • 9 Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. lei.chen@sjtu.edu.cn.
  • 10 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA. marc.schneebergerpane@yale.edu.
  • 11 State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China. xiaofei_yu@fudan.edu.cn.
  • 12 Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, China. xiaofei_yu@fudan.edu.cn.
  • # Contributed equally.
PMID: 39030389 DOI: 10.1038/s42255-024-01068-x
Abstract

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.

Figures
Products