Dietary anthocyanins alleviate age-dependent hepatic steatosis by expanding Limosilactobacillus reuteri and modulating gut microbiota–bile acid–hepatic FXR signaling

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent in aging populations. Dietary anthocyanins have been shown to exert metabolic benefits in aging and age-associated metabolic disorders. However, its role in protecting against age-dependent hepatic steatosis and the underlying mechanisms remain poorly defined. APPROACH AND RESULTS: In 18-month-old mice, dietary cyanidin-3-O-β-glucoside (Cy-3-G) markedly reduced hepatic triglyceride accumulation and improved serum liver enzyme levels without altering systemic glucose metabolism, body composition, or muscle function. Transcriptomic and pathway analyses identified hepatic farnesoid X receptor (FXR) signaling as the primary mediator of Cy-3-G-induced improvements in lipid metabolism. Studies in hepatocyte-specific FXR knockout mice confirmed that this pathway is essential, while in vitro assays showed that Cy-3-G does not directly activate FXR in hepatocytes, underscoring the importance of microbiota-derived signals. Notably, Limosilactobacillus reuteri was identified as a key bacterium expanded by Cy-3-G, which increased bile salt hydrolase activity and promoted the breakdown of FXR-inhibitory tauro-β-MCA. Fecal microbiota transfer, synthetic community cultures, and direct L. reuteri supplementation further validated its causal role in lowering tauro-β-MCA and improving hepatic steatosis. CONCLUSIONS: Cy-3-G alleviates age-dependent hepatic steatosis by selectively promoting L. reuteri expansion and reshaping bile acid composition to activate hepatic FXR signaling. These findings identify a gut microbiota-mediated mechanism by which a dietary anthocyanin mitigates age-related MASLD.