Raspberry aqueous extract ameliorates MAFLD in mice by regulating gut microbiota and purine metabolism.

Introduction: Metabolism-associated fatty liver disease (MAFLD) has emerged as a severe worldwide public health burden with insufficient available clinical therapeutic strategies, which underscores the urgent demand for safe, natural dietary interventions. Raspberry ( Methods: In this study, raspberry aqueous extract (RE) was prepared to comprehensively investigate its ameliorative effects and underlying molecular mechanisms against MAFLD. MAFLD animal model was established in C57BL/6 mice via 12-week high-fat diet (HFD) feeding. From the 9th week, model mice were intragastrically administered with RE at doses of 1 g/kg/d and 2 g/kg/d for continuous intervention. Integrated multi-omics analyses including 16S rRNA microbial sequencing, serum/hepatic biochemical detection, histopathological examination, in vivo microbial colonization assay, and in vitro cellular and metabolomic experiments were performed to systematically clarify the regulatory mechanism. Results: RE treatment markedly improved the core pathological phenotypes of MAFLD mice, and significantly mitigated hepatic steatosis and hepatocellular injury. 16S rRNA sequencing demonstrated that RE remodeled the gut microbial dysbiosis, specifically elevating the abundance of beneficial genus Discussion: Collectively, our results elucidate that raspberry aqueous extract alleviates experimental MAFLD through the gut microbiota-purine metabolism-inosine regulatory axis, in which Ileibacterium and inosine act as the core synergistic mediators. This study provides solid preclinical experimental evidence for the development and application of raspberry as a promising functional food for the prevention and nutritional intervention of MAFLD.