Yi Mai Granule Improves High‐Fat Diet–Induced Nonalcoholic Fatty Liver Disease in Mice by Regulating Gut Microbiota and Metabolites

Yi Mai granule (YMG) is a traditional Chinese medicine (TCM) herbal decoction consisting of two TCM formulas: Gua-Lou-Ban-Xia decoction and Si-Jun-Zi decoction. YMG has shown clinical benefit in the treatment of nonalcoholic fatty liver disease (NAFLD), which may be due to its regulatory effects on lipid metabolism. Previous studies have highlighted the importance of the gut microbiota and its metabolites in the use of TCM. However, the effect of YMG on the gut microbiota in the treatment of NAFLD remains unclear. In this study, we established an NAFLD model in <i>ApoE^-/-</i> mice and treated them with YMG. High-performance liquid chromatography was adopted to identify the chemical components of YMG. By mapping the candidate targets using network pharmacology, we found that the targets of the main components of YMG were significantly enriched in NAFLD-related pathways. Moreover, <i>16S rRNA</i> gene sequencing revealed that YMG affected the constitution and metabolism of the gut microbiota in NAFLD model mice, including lipid and carbohydrate metabolism. Similarly, metabolites related to lipid and carbohydrate metabolism in mouse serum were significantly altered by YMG. The correlation heat map and network analyses showed that the gut microbiota and metabolites affected by YMG were closely related to the blood lipid content. Collectively, YMG may exert therapeutic effects by affecting the metabolism of gut microbiota, thus regulating lipid and carbohydrate metabolism. These findings offer novel insight into the pharmacological mechanism of YMG in the treatment of NAFLD and provide theoretical bases for its clinical applications.