ArticleFrontiers in pharmacology2026
Hyodeoxycholic acid ameliorates tacrolimus-induced diabetes by modulating the FXR-FGF15 axis.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Backgroud: Immunosuppressant tacrolimus (TAC) induces glucose metabolism disorder and diabetes mellitus (DM) closely associated with intestinal microbiota dysbiosis and reduced bile acid levels, and this study aimed to explore the ameliorative effect and underlying mechanism of hyodeoxycholic acid (HDCA) on TAC-induced DM in rat models. Methods: We first verified the critical role of intestinal microbiota and bile acids in the pathogenesis of TAC-induced DM via antibiotic-induced gut microbiota depletion, then orally administered HDCA (100 mg/kg) to TAC-induced diabetic rats to evaluate its protective efficacy, detecting glycolipid metabolism indices, targeted bile acid omics, FXR/TGR5 protein expression, serum and ileal GLP/FGF15 levels, and mRNA levels of key metabolic genes including Results: Antibiotic treatment significantly reduced BSH-active gut microbiota such as Conclusions: Collectively, HDCA exerts a significant ameliorative effect on TACinduced DM by regulating metabolic enzymes and altering bile acid profiles, with the core mechanism involving inhibited enterohepatic FXR-FGF15 axis, increased GLP-1 secretion and suppressed hepatic gluconeogenesis, all of which play key regulatory roles in this protective process.
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