Changes Of Intestinal Flora In Patients With Extrahepatic Cholangiocarcinoma And Analysis Of Its Influencing Factors

ObjectiveStudy the variation of the specificity of the intestinal flora in patients with extrahepatic cholangiocarcinoma,and analyzed the influencing factors of intestinal flora in patients with extrahepatic cholangiocarcinoma,and hope to provide reliable theory basis from the perspective of intestinal flora.MethodsA total of 26 stool samples were collected from hospitalized patients in the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2020,including 16 patients with extrahepatic cholangiocarcinoma and 20 patients with common bile duct stones.The same period was collected.Stool samples of 10 healthy adults who were examined in the First Affiliated Hospital of Zhengzhou University.Statistics of the clinical data of the extrahepatic cholangiocarcinoma group,common bile duct stones group,and healthy group,as well as the treatment of drugs(including acid inhibitors,antibiotics and hepatoprotective drugs)and percutaneous liver puncture biliary drainage.Using the bacterial 16Sr RNA absolute quantitative sequencing technology to analyze the intestinal flora diversity and species structure of the three groups of research subjects,and then use LEfSe analysis to find out the significant enrichment of the extrahepatic cholangiocarcinoma group,Spearman correlation analysis was used to analyze the correlation between different bacterial groups,clinical indicators and drug use.Results1.There was no significant difference in age and gender between the extrahepatic cholangiocarcinoma group,the common bile duct stones group and the healthy group(P>0.05),while the liver function indexes were statistically different between the three groups(P<0.05).The comparison between the two groups found that compared with the common bile duct stones group,the extrahepatic cholangiocarcinoma group had no significant differences in alanine aminotransferase,aspartate aminotransferase and γ-glutamyl transpeptidase(all P>0.05).The total bilirubin,direct bilirubin,and alkaline phosphatase in the extrahepatic cholangiocarcinoma group were significantly higher than those in the common bile duct stones group,and the difference was statistically significant(all P<0.05).Compared with the healthy group,the extrahepatic cholangiocarcinoma group showed statistical differences in liver function indexes(all P<0.05).2.A diversity analysis showed that the Observed species and Chaol indexes of the three groups of extrahepatic cholangiocarcinoma,healthy and common bile duct stones were not statistically different(all P>0.05),while the Shannon index was statistically different(P<0.05).The comparison between the two groups showed that the Shannon index of the extrahepatic cholangiocarcinoma group was similar to that of the healthy group(P>0.05),but higher than that of the common bile duct stones group(P<0.05);β diversity analysis showed the difference in the composition of the gallbladder of the extrahepatic cholangiocarcinoma group and common bile duct stones group and healthy group(P<0.05)3.Analysis of significant differences between groups(LEfSe analysis)shows that Prevotella,Lactobacillus,Megasphaera,Sutterella were significantly enriched in the extrahepatic cholangiocarcinoma group(all P<0.05).4.Correlation analysis(Spearman correlation analysis)between differential flora and clinical indicators and drug use shows that Prevotella was negatively correlated with the use of antibiotics,acid inhibitors and hepatoprotective drugs(all r<0,P<0.05);Lactobacillus,Megasphaera,Sutterella are positively correlated with total bilirubin and direct bilirubin(all r>0,P<0.05).In addition,Lactobacillus is also positively correlated with alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,y-glutamy transpeptidase and age(all r>0,P<0.05),Megasphaera and alkaline phosphatase are positively correlated(r>0,P<0.05),Sutterella and aspartame aminotransferase are positively correlated(r>0,P<0.05).Conclusion1.Compared with healthy people and patients with common bile duct stones,the intestinal flora of patients with extrahepatic cholangiocarcinoma has undergone significant changes,mainly including Prevotella,Lactobacillus,Megasphaera and Sutterella were significantly enriched.2.The change of intestinal flora in patients with extrahepatic cholangiocarcinoma is closely related to the progression of the disease and the use of drugs.