Multi-omics analysis reveals gut microbiota remodeling and lipid metabolism regulation during the treatment of nonalcoholic fatty liver disease with Yindan Pinggan capsule

Background Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disorder with limited treatment options. Yindan Pinggan capsule (YDPG), a traditional Chinese medicine, has demonstrated potential in managing liver diseases, yet its efficacy and mechanisms in NAFLD remain unclear. Methods A high-fat diet (HFD)-induced NAFLD mouse model was established. The major bioactive components of YDPG, including baicalin, geniposide, and glycyrrhizic acid, were quantified using UPLC-QQQ-MS/MS. Integrated 16S rRNA sequencing and serum metabolomics were employed to analyze gut microbiota and metabolic profiles. qPCR was used to assess gene expression related to lipid metabolism. Results YDPG treatment significantly reduced body weight, liver index, hepatic lipid accumulation, inflammation, and improved serum lipid profiles and liver function (AST/ALT). It reshaped gut microbiota by decreasing harmful genera (e.g., Clostridioides, Ileibacterium) and enriching beneficial ones (e.g., Dubosiella), while regulating key metabolites involving bile acids, short-chain fatty acids, and neurotransmitters. qPCR confirmed modulation of lipid metabolism genes (e.g., Pparg, Cyp7a1, Hmgcr). Conclusions YDPG alleviates NAFLD by modulating the gut-liver axis, restoring gut microbial balance, and correcting metabolic disorders, demonstrating its potential as a multi-target therapeutic agent for NAFLD.