Investigation of “Microbial-mitochondrial” cross-talk to explore the compatibility mechanism of Xiaojianzhong Tang against chronic atrophic gastritis rats

Chronic atrophic gastritis (CAG) is one of the common digestive disorders. Xiaojianzhong Tang (XJZ) is a classic traditional Chinese medicine prescription (TCMP) used for the treatment of chronic atrophic gastritis, but its compatibility mechanism has not been fully clarified. This study integrated 16S rRNA sequencing, metabolomics, and molecular docking to explore the role of “Microbial mitochondrial” cross-talk in the treatment of CAG with XJZ and its subtracted formulas. CAG could cause disorders in gastric mucosal microbiota and gastric tissue metabolism. 17 gastric tissue differential metabolites were directly or indirectly derived from microbes and were associated with mitochondrial function. Further research had found that CAG could also cause mitochondrial metabolic disorders, with 18 mitochondrial metabolites involved in purine metabolism, glutathione metabolism, biosynthesis of various other secondary metabolites, nicotinate and nicotinamide metabolism, and aminoacyl-tRNA biosynthesis. XJZ showed the strongest effect, followed by XJZ-C (XJZ without “complement drug”) and XJZ-A (XJZ without “assistant drug”), and XJZ-P (XJZ without “principal drug”) the least. Protein-protein interaction (PPI) and molecular docking showed that mitochondrial metabolic enzymes could be potentially affected by microbial metabolites. In conclusion, there was a cross-talk between gastric mucosal microbes and mitochondria. In the treatment of CAG by XJZ, “principal drug” was the most important, and “assistant drug” and “complement drug” could assist the “principal drug”.