Bile acid metabolism involved into the therapeutic action of Xiaojianzhong Tang via gut microbiota to treat chronic atrophic gastritis in rats

Background: As a classical traditional Chinese medicine (TCM), Xiaojianzhong Tang (XJZ) is effective in treating chronic atrophic gastritis (CAG). However, the pharmacological mechanism of XJZ has not been fully explained. Purpose: The purpose of this study was to investigate the mechanism of XJZ against CAG rats via gut microbiome using a multi-omics approach. Methods: The rat cecal contents were analyzed through the integration of an untargeted metabolomic approach based on ultra-high performance liquid chromatography coupled with the quadrupole-time of flight mass spectrometry (UHPLC-QTOF-MS) and 16S rRNA gene sequencing. Finally, the interaction of differential metabolites with bile acid (BA)-related targets was verified by molecular docking. Results: A new strategy was adopted to screen out the differential metabolites based on the comprehensive evaluation of VIP, |log2(FC)|, -ln(p-value) and |p(corr)|. As results, XJZ showed favor regulations on the screened metabolites, cholic acid, deoxycholic acid, glycoursodeoxycholic acid, taurochenodesoxycholic acid, docosahexaenoic acid and L-isoleucine. The 16S rRNA gene sequencing analysis showed that XJZ could regulate gut microbiota disturbances in CAG rats, especially bile acid (BA) metabolism-related bacteria (Butyricimonas, Desulfovibrio, Bacteroides, Parabacteroides, Acetobacter and Alistipes). Molecular docking further showed that the differential metabolites regulated by XJZ had a good docking effect on BA-related targets. Conclusion: The current work indicated that XJZ's therapeutic action was strongly linked to BA-related microorganisms and metabolic processes. These findings provided new insights into the effects of XJZ for the treatment of CAG.