A multi-herb botanical formula ameliorates diet-induced non-alcoholic fatty liver disease associated with microbiota-dependent metabolic remodeling in mice.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbial dysbiosis and metabolic dysfunction, yet effective and sustainable therapeutic options remain limited. Wuqing Decoction (WQT), a multi-herb botanical formula containing Pueraria lobata and other medicinal and edible components, has shown metabolic regulatory potential, but its mechanistic basis in NAFLD remains unclear. Here, we evaluated the preventive and therapeutic effects of WQT in high-fat diet (HFD)-induced NAFLD mice and examined its microbiota-dependent mechanisms. WQT significantly alleviated hepatic steatosis, improved serum lipid profiles and liver injury markers, and reduced systemic inflammation, with more pronounced effects observed under preventive administration. Multi-omics analyses showed that WQT increased gut microbial diversity, altered community composition, and enriched beneficial taxa such as Akkermansia, Lactobacillus, and Ligilactobacillus. These changes were accompanied by coordinated shifts in fecal metabolites, including short-chain fatty acids, bile acid-related metabolites, and microbiota-derived phytochemical metabolites such as ginsenoside C-K. Hepatic transcriptomic profiling further demonstrated significant enrichment of fatty acid degradation and PPAR signaling pathways, indicating enhanced lipid catabolism and metabolic reprogramming. Importantly, antibiotic-mediated microbiota depletion markedly attenuated the metabolic, metabolomic, and transcriptional responses to WQT, whereas fecal microbiota transplantation partially restored these effects, supporting a microbiota-dependent mechanism. Collectively, these findings suggest that WQT ameliorates NAFLD through microbiota-dependent metabolic remodeling, which is associated with activation of the hepatic PPAR signaling network, highlighting its potential as a microbiota-targeted botanical intervention for metabolic liver disease.