Antibiotic‐Mediated Microbiota Depletion Suggests an Association Between Gastric Juice Dysbacteriosis and Abnormal Bile Acid Metabolism in Chronic Atrophic Gastritis Rats

Current research on chronic atrophic gastritis (CAG) has primarily focused on intestinal flora, while the role of gastric juice microecology remains poorly understood. This study investigated whether alterations in gastric juice microbiota and bile acid (BA) profiles are associated with CAG under microbiota perturbation. A CAG rat model was designed by a multifactor modeling method, and an antibiotic cocktail (Abx) was administered to deplete gastrointestinal microbiota. Full-length 16S rRNA gene sequencing and LC-MS technology were conducted to characterize microbial composition and metabolite profiles in gastric juice. An integrated strategy combining microbiome and metabolome data was employed to validate associations between microbiota and metabolites. CAG rats exhibited elevated proinflammatory cytokines and lipopolysaccharide (LPS) levels in gastric juice, accompanied by dysbacteriosis and aberrant BA profiles. After antibiotic treatment, LPS level and bile salt hydrolase (BSH) activity were reduced, along with the lower abundances of LPS-producing bacteria and multiple BA levels. Correlation analysis demonstrated a positive association between deoxycholic acid (DCA) and LPS-producing bacteria (Escherichia coli). These findings revealed that gastric juice dysbacteriosis and abnormal BA metabolism were relevant to the inflammatory status of CAG. This study provided multi-omics evidence supporting a potential involvement of gastric juice microecological imbalance in CAG progression.