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

Abstract 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, serum metabolomics, and liver transcriptomics were employed to analyze gut microbiota and metabolic profiles, and gene expression. qPCR was used to evaluate the expression of key regulatory genes. Results YDPG treatment significantly reduced body weight, liver index, hepatic lipid accumulation, and inflammation, while improving serum lipid profiles and liver function (AST/ALT). Integrated multi-omics analyses revealed that YDPG 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. Liver transcriptome profiling further identified that YDPG exerted its effects primarily through the PPAR signaling pathway and primary bile acid biosynthesis pathway. These findings were confirmed by qPCR, which validated the modulation of key genes (Pparg, Scd1, Cyp7a1, Cyp39a1) involved in the relevant pathways. 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.