Stachyose Attenuates Hepatic Cholesterol Deposition in Nonalcoholic Fatty Liver Mice via Gut Microbiota-Driven Bile Acid Profile Remodeling.

Nonalcoholic fatty liver disease (NAFLD), driven by liver lipid accumulation, presents a global health challenge. Bile acid metabolism critically regulates cholesterol homeostasis, but whether prebiotic stachyose can modulate it for NAFLD intervention is unknown. In NAFLD mice induced by a high-fat-high-sucrose diet, stachyose (200 mg/kg bw, 20 weeks) expanded the bile acid pool, elevating the primary bile acids (such as cholic acid and chenodeoxycholic acids) in both serum and liver while reducing secondary bile acid levels. Mechanistically, stachyose upregulated the expression of bile acid synthesis enzymes CYP7A1 and CYP27A1 by inactivating the farnesoid X receptor (FXR)-small heterodimer partner (SHP) pathway, attributed to reducing the high-affinity ligand taurodeoxycholic acid level. Concurrently, it suppressed gut bile salt hydrolase (BSH) and 7α-dehydroxylase (7α-DH) activities, along with Bacteroides abundance, thereby suppressing secondary bile acid biotransformation. In conclusion, these findings highlight stachyose's ability to restore bile acid homeostasis in NAFLD, providing a novel theoretical basis for preventive and therapeutic strategies.