Integrated analysis of NAFLD mitigation mechanism by Ganoderma lucidum insoluble dietary fiber based on transcriptomics, metabolomics and gut microbiota

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, modulating lipid disorders, and improving oxidative stress. Furthermore, GIDF likely regulated lipid metabolism through pathways such as Cytochrome P450, Retinol metabolism, and Peroxisome Proliferator-Activated Receptor 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 , Blautia , Clostridium , and Akkermansia .The results from the co-administration of antibiotics and GIDF further demonstrated that the ameliorative effects of GIDF on NAFLD are dependent on the presence of gut microbiota. Metabolomic analysis indicated that GIDF upregulated levels of L-cysteine, S-adenosylmethionine (SAMe), and 5'-methylthioadenosine (MTA), while downregulating 13(S)-HODE, thereby modulating amino acid and lipid metabolism. These findings validate that GIDF alleviates NAFLD via the gut-liver axis and may serve as a promising nutritional supplement.