Characteristics Of Gastric Flora And Changes Of Bile Acid Metabolism In Patients With Bile Reflux Gastritis

BackgroundBile reflux gastritis(BRG)can cause inflammation,gastric mucosa atrophy,and diseases such as stomach cancer.Alkaline bile flowing back into the stomach affects the intragastric environment and can alter the gastric bacterial community.Besides,the composition of conjugated bile acids in the stomach increased significantly in patients with bile reflux,suggesting that due to the particularity of the gastric environment,bile acid profile may have changed during the process of bile flowing back into the stomach after entering the intestine,which may then affect the entire bile acid pool.Further investigation of gastric microbiota and bile acid metabolism is helpful to reveal the pathogenesis of BRG.AimsWe sought to identify the characteristics of the stomach mucosal microbiota in patients with BRG,the change of bile acid profile during bile reflux,and the characteristics of the serum bile acid profile in to further search for biomarkers in the diagnosis of BRG.MethodsPatients with chronic gastritis patients with and without bile reflux were recruited.Serum samples,mucosa samples and gastric fluid samples were collected.Patients undergoing nasobiliary drainage due to choledocholithiasis were recruited and bile duct samples were collected.16S-rRNA gene analysis was used to determine the bacterial profile in patients with and without bile reflux.LS-MC analysis was used to determine the difference of bile acid profile between bile reflux and bile duct bile and to explore the characteristics of serum bile acid in patients with bile reflux.ResultsIn the absence of H.pylori infection,the richness(based on the Sobs and Chaol indices;P<0.05)and diversity(based on Shannon indices;P<0.05)of gastric mucosa microbiota were higher in patients with bile reflux patients than in those without.There was a marked difference in the microbiota structure between patients with and without bile reflux(ANOSIM,R=0.058,P=0.011).While the genera,Comamonas,Halomonas,Bradymonas,Pseudomonas,Marinobacter,Arthrobacter,and Shewanella were enriched in patients with bile reflux,the genera,Haemophilus,Porphyromonas,and Subdoligranulum,were enriched in those without bile reflux.Compared with bile duct bile,the concentration of total bile acid in gastric bile was significantly decreased.The proportion of isoLCA,HCA,and UDCA decreased significantly(P<0.01;P<0.001;P<0.01).The serum bile acid profile in patients with bile reflux was significantly changed,and binary logistic regression analysis suggested that Total free bile acid and DCA were independent risk factors for bile reflux gastritis(P<0.05;P<0.01).ROC curve analysis suggested that the ratio of GHCA to total BAs was a good biomarker for the diagnosis of BRG,with a sensitivity of 85.7%and a specificity of 85.7%.ConclusionOur results demonstrate that bile reflux significantly alters the composition of the gastric microbiota and may be characterized by the disorder of bile acid metabolism.Gastric microbiota changes and bile acid metabolism disorders may play an important role in the pathogenesis of BRG.Gastric microbiota changes associated with bile reflux are expected to be potential therapeutic targets for this disease.Detection of serum bile acid profile provides a new direction for clinical non-invasive diagnosis of BRG.