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

ABSTRACT 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.