A Gly-β-muricholic acid and FGF15 combination therapy synergistically reduces "humanized" bile acid pool toxicity in cholestasis mice.

ABSTRACT: Hydrophobic bile acid-mediated hepatobiliary injury is a major driver of cholestasis progression. Most anticholestasis treatments being tested clinically are based on a single agent, which does not always sufficiently alleviate bile acid toxicity to slow disease progression. This study investigates a therapeutic strategy of combining glycine-conjugated β-muricholic acid (Gly-βMCA) and fibroblast growth factor-15 (FGF15) to alleviate bile acid hepatobiliary toxicity in Cyp2c70 KO mice that lack endogenous muricholic acid (MCA) synthesis and have a "humanized" hydrophobic bile acid pool composition. The effects of the single and combination treatments on bile acid metabolism, liver injury, and gut microbiome were investigated in female Cyp2c70 KO mice with progressive cholangiopathy and port

SUBMITTER: Hasan MN 

PROVIDER: S-EPMC12702073 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature