Abstract
INTRODUCTION: The gut microbiota and bile acids (BAs) have emerged as factors involved in the development of non-alcoholic fatty liver disease (NAFLD). Xiaohua Funing decoction (XFD) is a traditional Chinese medicine formula used for the treatment of NAFLD. Previous studies have indicated that XFD protects liver function, but the underlying mechanism remains unclear. METHODS: In this study, a Wistar rat model of NAFLD (Mod) was established via a high-fat diet. The effects of obeticholic acid (OCA) and XFD on Mod rats were subsequently evaluated. Wistar rats in the control (Con) group were fed a standard diet. There were eight rats in each group, and the treatment lasted for 12 weeks. Furthermore, metagenomic sequencing and BA metabolomic analyses were performed. RESULTS: Compared to the Con group, the Mod group presented significant differences in body and liver weights; serum total cholesterol (TC) and triglyceride (TG) levels; and liver TG, TC, and bile salt hydrolase levels (p < 0.05 or p < 0.01). Importantly, OCA and XFD administration normalized these indicators (p < 0.05 or p < 0.01). Pathology of the liver and white fat steatosis was observed in the Mod group, but steatosis was significantly alleviated in the OCA and XFD groups (p < 0.05 or p < 0.01). The abundances of Bacteroidales_bacterium, Prevotella_sp., bacterium_0.1xD8-71, and unclassified_g_Turicibacter in the Mod group were significantly different from those in the Con group (p < 0.05 or p < 0.01), whereas the abundance of Bacteroidales_bacterium was greater in the XFD group. A total of 17, 24, and 24 differentially abundant BAs were detected in the feces, liver, and serum samples from the Mod and Con groups, respectively (p < 0.05 or p < 0.01). In the feces, liver, and serum, XFD normalized the levels of 16, 23, and 14 BAs, respectively, including glycochenodeoxycholic acid, deoxycholic acid, murideoxycholic acid, lithocholic acid, 23-nordeoxycholic acid, and 3β-ursodeoxycholic acid. In addition, glycochenodeoxycholic acid was identified as a potential biomarker of NAFLD. DISCUSSION: In summary, our experiments revealed that XFD regulates the gut microbiota and BAs, providing beneficial effects on liver lipid accumulation in NAFLD.