肠道菌群在胆道良性疾病中致病作用的全基因组孟德尔随机化研究  

Genome-wide Mendelian randomization study of the pathogenic role of gut microbiota in benign biliary tract diseases

作　　者：赵经委 侯煜铖 杨自逸 周哲 龚伟[1] Zhao Jingwei;Hou Yucheng;Yang Ziyi;Zhou Zhe;Gong Wei(Department of General Surgery,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Biliary Tract Disease Research Research Institute of Biliary Tract Disease Shanghai Research Center of Tract Disease,Shanghai 200092,China;Department of Cardiovascular Surgery,the First Affiliated Hospital of Soochow University,Suzhou 215006,China)

机构地区：[1]上海交通大学医学院附属新华医院普外科、上海市胆道疾病研究重点实验室、上海交通大学医学院胆道疾病研究所、上海市胆道疾病研究中心,上海200092 [2]苏州大学附属第一医院心脏大血管外科,苏州215006

出　　处：《中华外科杂志》2024年第3期216-222,共7页Chinese Journal of Surgery

基　　金：国家自然科学基金(82172628);上海市胆道疾病研究重点实验室基金项目(17DZ2260200)。

摘　　要：目的通过全基因组孟德尔随机化分析探究肠道菌群和胆道良性疾病的因果关系。方法本研究为回顾性观察性研究。选择MiBioGen联盟中18340个样本的肠道菌群全基因组关联研究数据作为暴露组,从FinnGen联盟R8获取胆道疾病全基因组关联研究数据作为结局组,包括1491例原发性硬化性胆管炎、32894例胆石症、3770例非结石性胆囊炎和34461例胆囊炎病例。筛选单核苷酸多态性作为工具变量,采用孟德尔随机化方法推定暴露与结局的因果关系,以逆方差加权法(IVW)作为主要依据,辅以异质性、多效性和灵敏性检验。结果Coprococcus 2属与胆石症(IVW OR=0.88,95%CI:0.80~0.97,P=0.012)、广义胆囊炎(IVW OR=0.88,95%CI:0.80~0.97,P=0.011)风险降低有关;Coprococcus 3属与胆石症(IVW OR=1.15,95%CI:1.02~1.30,P=0.019)、非胆石性胆囊炎(IVW OR=1.48,95%CI:1.08~2.04,P=0.016)和广义胆囊炎(IVW OR=1.17,95%CI:1.02~1.33,P=0.020)风险增加有关;Peptococcus属与胆石症(IVW OR=1.08,95%CI:1.02~1.13,P=0.005)、广义胆囊炎(IVW OR=1.07,95%CI:1.02~1.13,P=0.010)风险增加有关;Clostridiumsensustricto 1属与胆石症(IVW OR=1.16,95%CI:1.02~1.31,P=0.020)、广义胆囊炎(IVW OR=1.16,95%CI:1.03~1.30,P=0.015)风险增加有关。Eubacterium hallii属与原发性硬化性胆管炎(IVW OR=1.43,95%CI:1.03~1.99,P=0.033)风险增加有关;Eubacterium ruminantium属(IVW OR=0.87,95%CI:0.76~1.00,P=0.043)和Methanobrevibacter属(IVW OR=0.81,95%CI:0.68~0.98,P=0.027)与非胆石性胆囊炎风险降低有关。结论8种肠道菌属可能在胆道良性疾病中有致病作用,其中Eubacterium hallii属会导致原发性硬化性胆管炎发生风险增加,Peptococcus属会导致胆石症、广义胆囊炎发生风险增加,Clostridiumsensustricto 1属会导致胆石症、广义胆囊炎发生风险增加,Coprococcus 3属与胆石症、广义胆囊炎具有多重相关性。Objective To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization.Methods This is a retrospective observational study.The data from the genome-wide association study of the gut microbiota from 18340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group.There were 1491 cases of primary sclerosing cholangitis,32894 cases of cholelithiasis,3770 cases of acalculous cholecystitis,and 34461 cases of cholecystitis.Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes.The inverse variance weighting method(IVW)was used as the main basis,supplemented by heterogeneity,pleiotropy and sensitivity tests.Results Coprococcus 2 was associated with a reduced risk of cholelithiasis(IVW OR=0.88,95%CI:0.80 to 0.97,P=0.012)and cholecystitis(IVW OR=0.88,95%CI:0.80 to 0.97,P=0.011).Coprococcus 3 was associated with cholelithiasis(IVW OR=1.15,95%CI:1.02 to 1.30,P=0.019)and acalculous cholecystitis(IVW OR=1.48,95%CI:1.08 to 2.04,P=0.016)and cholecystitis(IVW OR=1.17,95%CI:1.02 to 1.33,P=0.020).Peptococcus was associated with an increased risk of cholelithiasis(IVW OR=1.08,95%CI:1.02 to 1.13,P=0.005)and cholecystitis(IVW CI=1.07,95%CI:1.02 to 1.13,P=0.010).Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis(IVW OR=1.16,95%CI:1.02 to 1.31,P=0.020)and cholecystitis(IVW OR=1.16,95%CI:1.03 to 1.30,P=0.015).Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis(IVW OR=1.43,95%CI:1.03 to 1.99,P=0.033).Eubacterium ruminantium(IVW OR=0.87,95%CI:0.76 to 1.00,P=0.043)and Methanobrevibacter(IVW OR=0.81,95%CI:0.68 to 0.98,P=0.027)were associated with a reduced risk of acalculous cholecystitis.Conclusions Eight intestinal bact

关 键 词：胆道疾病 胆囊炎 孟德尔随机化 肠道菌群 良性疾病 胆石症 

分 类 号：R575[医药卫生—消化系统]