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.

肠道菌群失调与代谢综合征 (MetS) 的发病机制有关，并可能通过有害代谢物损害宿主代谢。在这里，我们发现Desulfovibrio是一种在 MetS 患者体内富集的肠道共生体，它通过在雄性小鼠中产生硫化氢 (H ₂ S) 来抑制肠道激素胰高血糖素样肽 1 (GLP-1) 的产生。研究发现，脱硫弧菌衍生的 H ₂ S 可抑制线粒体呼吸并诱导肠道 L 细胞中的未折叠蛋白反应，从而阻碍 GLP-1 分泌和基因表达。值得注意的是，用非处方药次水杨酸铋阻断Desulfovibrio和 H ₂ S，可以改善雄性小鼠 GLP-1 的产生并改善饮食诱导的代谢紊乱。总之，我们的研究发现脱硫弧菌衍生的 H ₂ S 会损害 GLP-1 的产生，揭示了有害微生物群衍生代谢物通过肠道中继机制损害 MetS 中的宿主代谢，并提出了治疗 MetS 的新可能性。