Quyu Huazhuo Decoction alleviates non-Alcoholic steatohepatitis via remodeling the gut microbiota and regulating bile acid and short-chain fatty acid metabolism.

Non-alcoholic steatohepatitis (NASH), a globally prevalent metabolic disorder, exhibits a complex and incompletely understood pathogenesis with limited clinical treatment options available. Studies have shown that Quyu Huazhuo Decoction (QYHZD) can effectively reduce insulin resistance and improve liver function in NASH patients, though its underlying mechanisms remain unclear. Using a high-fat diet (HFD)-induced NASH rat model, the present study employed 16S rDNA sequencing along with targeted metabolomics of bile acids (BAs) and short-chain fatty acids (SCFAs) to systematically evaluate the therapeutic effects of QYHZD. The results showed that QYHZD significantly alleviated HFD-induced obesity, hepatic steatosis, inflammatory response, and glucose and lipid metabolism dysregulation. The intervention also reshaped the gut microbiota, promoting the growth of beneficial bacteria such as Akkermansia and Roseburia, while suppressing harmful taxa including Klebsiella and Desulfovibrio. Metabolomics analysis indicated that QYHZD intervention upregulated protective BAs (e.g., UDCA, CDCA, and their conjugated forms) and SCFAs (e.g., butyric acid and valeric acid), along with reduced production of toxic BAs such as DCA. In conclusion, this study revealed that QYHZD improves the progression of NASH through multi-axis regulation of "microbiota-BA/SCFA-metabolism", providing experimental evidence and mechanistic insights for the use of traditional Chinese medicine in treating metabolic liver diseases.