Lactococcus garvieae aggravates cholestatic liver disease by increasing intestinal permeability and enhancing bile acid reabsorption  

作　　者：Man Liu Ying-Lan Ji Yu-Jie Hu Ying-Xi Su Jie Yang Xiao-Yi Wang Hong-Yu Chu Xue Zhang Shi-Jing Dong Hui Yang Yu-Hang Liu Si-Min Zhou Li-Ping Guo Ying Ran Yan-Ni Li Jing-Wen Zhao Zhi-Guang Zhang Mei-Yu Piao Lu Zhou 

机构地区：[1]Department of Gastroenterology and Hepatology,General Hospital,Tianjin Medical University,Tianjin 300070,China [2]Department of Gastroenterology,The Second Hospital of Tianjin Medical University,Tianjin 300211,China [3]Department of Gastroenterology,Tianjin Medical University General Hospital Airport Hospital,Tianjin 300308,China [4]Department of Gastroenterology and Hepatology,Tianjin Third Central Hospital,Tianjin 300170,China

出　　处：《World Journal of Gastroenterology》2025年第10期103-117,共15页世界胃肠病学杂志(英文)

基　　金：Supported by Tianjin Health Research Project,No.TJWJ2024QN005;Beijing iGandan Public Welfare Foundation Artificial Liver Special Fund,No.iGandanF-1082024-RGG122.

摘　　要：BACKGROUND Although an association between gut microbiota and cholestatic liver disease(CLD)has been reported,the precise functional roles of these microbes in CLD pathogenesis remain largely unknown.AIM To explore the function of gut microbes in CLD pathogenesis and the effects of gut microbiota on intestinal barrier and bile acid(BA)metabolism in CLD.METHODS Male C57BL/6J mice were fed a 0.05%3,5-diethoxycarbonyl-1,4-dihydrocollidine diet for 2 weeks to induce CLD.The sterile liver tissues of mice were then meticulously harvested,and bacteria in homogenates were identified through culture methods.Furthermore,16S ribosomal DNA sequencing was employed to analyze sterile liver samples collected from eight patients with primary biliary cholangitis(PBC)and three control individuals with hepatic cysts.The functional roles of the identified bacteria in CLD pathogenesis were assessed through microbiota transfer experiments,involving the evaluation of changes in intestinal permeability and BA dynamics.RESULTS Ligilactobacillus murinus(L.murinus)and Lactococcus garvieae(L.garvieae)were isolated from the bacterial culture of livers from CLD mice.L.murinus was prevalently detected in PBC patients and controls,whereas L.garvieae was detected only in patients with PBC but not in controls.Mice inoculated with L.garvieae exhibited increased susceptibility to experimental CLD,with both in vitro and in vivo indicating that L.garvieae disrupted the intestinal barrier function by down-regulating the expression of occludin and zonula occludens-1.Moreover,L.garvieae administration significantly upregulated the expression of the apical sodium-dependent BA transporter in the terminal ileum and increased serum BA levels.CONCLUSION L.garvieae contributes to excessive BA-induced hepatobiliary injury and liver fibrosis by increasing intestinal permeability and enhancing BA reabsorption.

关 键 词：CHOLESTASIS MICROBIOTA Lactococcus garvieae Intestinal permeability Bile acid 

分 类 号：R575[医药卫生—消化系统]