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

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.