Noni fruit phenolic-rich extract ameliorated non-alcoholic fatty liver disease through regulating gut microbiota and bile acids profiling by targeting FXR-FGF15 signaling.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally, covering a spectrum from simple hepatic steatosis to steatohepatitis. With limited pharmacological interventions available, there is growing interest in natural products for NAFLD prevention and management. The farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway plays a pivotal role in regulating bile acid (BA) and lipid metabolism, and its dysregulation is closely linked to NAFLD progression. RESULTS: Noni fruit phenolic-rich extract (NFE) treatment ameliorated high-fat diet (HFD)-induced increases in body weight and lipid accumulation in both serum and hepatic tissues, accompanied by reduced serum aspartate aminotransferase and alanine aminotransferase activities, indicating improved hepatic function and reduced liver injury. Moreover, NFE intervention modulated the expression of key components of the FXR-FGF15 signaling pathway, leading to downregulation of hepatic CYP7A1 and subsequent modulation of BA and lipid metabolism. Notably, NFE intervention can modulate the gut microbiota and its metabolic functions, thereby sustaining BA homeostasis through feedback regulation of the FXR-FGF15 pathway. CONCLUSION: In summary, NFE intervention alleviates high-fat diet (HFD)-induced NAFLD by modulating the FXR-FGF15 pathway, regulating bile acid metabolism, and reshaping gut microbiota. These results support the potential application of NFE as a nutritional intervention for NAFLD. © 2026 Society of Chemical Industry.