Monascus pilosus SWM-008-Fermented Red Mold Rice and Its Monascinol Ameliorate Non-Alcoholic Fatty Liver Disease via Activation of the AMPK-ATGL Pathway and Enrichment of Butyrate-Producing Bacteria.

SWM-008 red mold rice, fermented by Monascus pilosus SWM-008, upregulates Akkermansia and supports gut barrier function and metabolic health, suggesting prebiotic-like and postbiotic-like effects. Its dual role suggests value for metabolic disorder management. Few interventions simultaneously enhance both Akkermansia and butyrate-producing bacteria, which underscores the unique potential of SWM-008. SWM-008 red mold rice, and its functional compound were administered to a high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) model in C57BL/6 mice for 18 weeks. In a HFD-induced NAFLD mouse model, SWM-008 and its bioactive compounds monascinol (Msol) and monascin (MS) reduced hepatic triglycerides (TG) (14.5% for SWM-008, 13.0% for Msol; p < 0.05), improved steatosis, and modulated gut microbiota. SWM-008 activated AMP-activated protein kinase (AMPK) and adipose triglyceride lipase (ATGL) while suppressing sterol regulatory element binding protein 1c (SREBP-1c) and fatty acid synthase (FASN), indicating reduced lipogenesis and enhanced lipolysis. Msol lowered cluster of differentiation 36 (CD36) and stimulated the AMPK/ATGL/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/carnitine palmitoyltransferase 1 (CPT-1) pathway. SWM-008 increased butyrate-producing Roseburia and Eubacterium, and Msol and MS raised fecal butyrate to over 2%, supporting gut-liver health. These findings support SWM-008 as a promising dietary strategy for gut-liver health in NAFLD.