Wei-Mi-Shu Decoction ameliorates gastric mucosal injury in chronic gastritis with liver-stomach disharmony syndrome through the gut microbiota-hepatic bile acid metabolism axis

Introduction Chronic gastritis (CG) is a high‐incidence disease in the digestive system, and liverstomach disharmony syndrome (LSD) is a relatively common syndrome type. This study aimed to evaluate the role and possible mechanism of traditional Chinese medicine Wei‐Mi‐Shu Decoction (WMS) in treating LSDCG. Methods The CG and LSDCG animal models were established and treated with WMS to observe the TCM syndrome scores and behavioral changes, histopathological alterations of the gastric mucosa, and expressions of pro‐inflammatory cytokines and tight junction proteins. Then, the changes of gut microbiota and bile acids (BAs) were analyzed by microbiota sequencing and mass spectrometry, and the protein expressions of BA receptors were detected by immunohistochemistry and WB. Finally, Lgr5‐positive (Lgr5 + ) gastric cells were observed by immunofluorescence staining, the expression of gastric mucosal cell differentiation markers was detected by RT‐qPCR, and the fatty acid oxidation (FAO) of Lgr5 + cells was observed by fluorescence double staining. Results WMS reduced the TCM syndrome scores, increased the autonomous activity ability, and improved gastric mucosal injury, inflammatory response, and gastric mucosal barrier disruption in the CG and LSDCG model rats. WMS also regulated the intestinal microbiota and BA metabolism of model rats, and promoted the levels of PPARα and RXR. In addition, WMS attenuated the loss of Lgr5 + gastric stem cells and promoted their differentiation and FAO. Conclusion In conclusion, WMS promoted the differentiation of Lgr5 + gastric stem cells, potentially involving the gut microbiotahepatic BA metabolism axis to repair gastric mucosal injury in LSDCG.