VSL#3 Co-Administration Is Associated with Altered Early-Phase Obeticholic Acid Exposure in MASLD Mice

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, and its global incidence continues to increase. MASLD can progress from simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, effective preventive and therapeutic options remain limited. In this study, obeticholic acid (OCA) and the probiotic mixture VSL#3 were co-administered to a mouse model of MASLD to modulate gut microbiota and bile acid metabolism.

Methods

Male C57BL/6 mice were fed a WD to induce MASLD and treated with OCA, VSL#3, or both. Gut microbiota was analyzed by 16S rRNA sequencing, bile acid (BA) composition was assessed by LC–MS/MS, hepatic and intestinal gene expression was determined by quantitative real-time PCR (qPCR) and immunohistochemistry, and unconjugated OCA pharmacokinetics (PK) were evaluated.