BACKGROUND Chronic biliary disease,including cholangitis and cholecystitis,is attributed to ascending infection by intestinal bacteria.Development of a mouse model for bile duct inflammation is imperative for the adva...BACKGROUND Chronic biliary disease,including cholangitis and cholecystitis,is attributed to ascending infection by intestinal bacteria.Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches.Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver.Therefore,we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases.AIM To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases.METHODS We established a mouse biliary disease model by directly connecting the gallbladder and duodenum,enabling ascending infection into the biliary tract without traversing the sphincter of Oddi.RESULTS In the cholecystoduodenal anastomosis mouse model,we observed impaired epithelial structure,wall thickening,and macrophage recruitment in the gallbladder.Despite the absence of postoperative antibiotics,we detected no changes in serum proinflammatory cytokine levels,indicating no systemic inflammation.Moreover,patency between the gallbladder and duodenum was confirmed via common bile duct ligation.Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection,which significantly increased proinflammatory cytokine mRNA expression in the liver,duodenum,and ileum.These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum,leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans.CONCLUSION The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.展开更多
基金Supported by Korea Health Technology R&D Project through the Korea Health Industry Development Institute,Funded by the Ministry of Health&Welfare,Republic of Korea,No.HR20C0025 and No.HI22C1212the National Research Foundation of Korea Grant Funded by the Korea Government,No.RS-2023-00238188。
文摘BACKGROUND Chronic biliary disease,including cholangitis and cholecystitis,is attributed to ascending infection by intestinal bacteria.Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches.Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver.Therefore,we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases.AIM To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases.METHODS We established a mouse biliary disease model by directly connecting the gallbladder and duodenum,enabling ascending infection into the biliary tract without traversing the sphincter of Oddi.RESULTS In the cholecystoduodenal anastomosis mouse model,we observed impaired epithelial structure,wall thickening,and macrophage recruitment in the gallbladder.Despite the absence of postoperative antibiotics,we detected no changes in serum proinflammatory cytokine levels,indicating no systemic inflammation.Moreover,patency between the gallbladder and duodenum was confirmed via common bile duct ligation.Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection,which significantly increased proinflammatory cytokine mRNA expression in the liver,duodenum,and ileum.These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum,leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans.CONCLUSION The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.
