Revealing the mechanism of Ganoderma lucidum insoluble dietary fiber alleviating NAFLD through transcriptomics and metabolomics.

The study established a mouse model of NAFLD induced by a 12-week high-fat diet (HFD). Utilizing hepatic transcriptomics, 16S rDNA sequencing, and metabolomics, the study examined the mechanisms by which GIDF exerts hepatic protection and modulates lipid metabolism in NAFLD through the gut-liver axis.The results demonstrated that GIDF supplementation significantly alleviated NAFLD characteristics in mice, including reducing biomarkers associated with hepatic lipid deposition and injury(Serum cholesterol, Serum triglycerides, lipopolysaccharide (LPS), TNF-α, etc.), modulating lipid disorders, and improving oxidative stress. GIDF likely regulated lipid metabolism through pathways such as Cytochrome P450, Retinol metabolism, and PPAR signaling, while increasing the expression of ileal tight junction proteins (ZO-1 and Occludin), thereby repairing the intestinal barrier.GIDF altered gut microbiota composition, promoting the growth of Lactobacillus and Akkermansia.Furthermore, GIDF upregulated levels of L-cysteine, S-adenosylmethionine (SAMe), and 5'-methylthioadenosine (MTA), while downregulating 13(S)-HODE. These findings validate that GIDF alleviates NAFLD and may serve as a promising nutritional supplement.