两样本孟德尔随机化分析肠道菌群与肝外胆管癌的因果关系  

Two-sample Mendelian randomization of the relationship between gut microbiota and the risk of extrahepatic cholangiocarcinoma

作　　者：王小磊 方骏 王安 朱武晖[1] 史光军[2] WANG Xiaolei;FANG Jun;WANG An;ZHU Wuhui;SHI Guangjun(Department of Hepatobiliary Surgery,Qingdao Third Peoples Hospital,Qingdao 266041,Shandong,China;Department of Hepatobiliary Surgery,Qingdao Municipal Hospital,Qingdao 266011,Shandong,China)

机构地区：[1]青岛市第三人民医院肝胆外科,山东青岛266041 [2]青岛市市立医院肝胆外科,山东青岛266011

出　　处：《山东大学学报(医学版)》2025年第4期44-50,共7页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金面上项目(ZR202103030420)。

摘　　要：目的采用两样本孟德尔随机化(Mendelian randomization,MR)方法评估肠道菌群与肝外胆管癌之间的因果关系。方法从MiBioGen数据库下载人类肠道菌群的全基因组关联研究(genome-wide association study,GWAS)数据作为暴露因素,从GWAS Catalog官网获取肝外胆管癌GWAS数据作为结局,使用随机效应逆方差加权法、加权中位数法、MR-Egger回归、简单模式和加权模式等5种方法进行MR分析,探索肠道菌群与肝外胆管癌发病风险之间的因果关系,并对MR结果进行敏感性分析、异质性检验、多效性检验,评估结果的可靠性和准确性。结果最终筛选出55个与肠道菌群有关的工具变量。MR结果显示颤螺菌属(OR=6.705,95%CI:1.612~27.890,P=0.009)、普氏菌属7(OR=2.565,95%CI:1.108~5.940,P=0.028)和Family_XIII_AD3011_group(OR=5.513,95%CI:1.186~25.620,P=0.029)与肝外胆管癌之间呈正向因果关系;氨基酸球菌科(OR=0.113,95%CI:0.026~0.500,P=0.004)、乳酸杆菌科(OR=0.349,95%CI:0.132~0.924,P=0.034)和丁酸弧菌属(OR=0.493,95%CI:0.252~0.963,P=0.039)与肝外胆管癌之间呈负向因果关系,同时MR Egger、加权中位数法、简单模式和加权模式与逆方差加权法的结果方向一致。敏感性分析结果提示不存在水平多效性及异质性,MR结果可靠。结论颤螺菌属、普氏菌属7、Family_XIII_AD3011_group、氨基酸球菌科、乳酸杆菌科和丁酸弧菌属与肝外胆管癌之间具有潜在因果关系。Objective To evaluate the causal relationship between gut microbiota and extrahepatic cholangiocarcinoma(ECC)by using two-sample Mendelian randomization(MR)analysis.Methods Genome-wide association study(GWAS)data of human gut microbiota were obtained from the official website of MiBioGen Alliance as exposure factors,and GWAS data of ECC were obtained from the official website of GWAS Catalog as the outcome.Five methods,including random effect inverse variance weighting,weighted median,MR-Egger regression,simple model and weighted model,were used to conduct two-sample MR to explore the causal relationship between gut microbiota and the risk of ECC.Sensitivity analysis,heterogeneity test and pleiotropy test were also conducted to evaluate the reliability and accuracy of the results.Results Finally,55 instrumental variables related to gut microbiota were selected.MR results showed that the Oscillospira(OR=6.705,95%CI:1.612-27.890,P=0.009),Prevotella 7(OR=2.565,95%CI:1.108-5.940,P=0.028)and Family_XIII_AD3011_group(OR=5.513,95%CI:1.186-25.620,P=0.029)were positively correlated with ECC.There was a negative causal relationship between Acidaminococcaceae(OR=0.113,95%CI:0.026-0.500,P=0.004),Lactobacillaceae(OR=0.349,95%CI:0.132-0.924,P=0.034),Butyrivibrio(OR=0.493,95%CI:0.252-0.963,P=0.039)and ECC.The direction of MR Egger,weighted median method,simple model and weighted model was consistent with inverse variance weighted method.Sensitivity analysis showed no horizontal pleiotropy and heterogeneity,and MR results were reliable.Conclusion There is a potential causal relationship between Oscillospira,Prevotella 7,Family_XIII_AD3011_group,Acidaminococcaceae,Lactobacillaceae,Butyrivibrio and ECC.

关 键 词：肠道菌群 肝外胆管癌 孟德尔随机化 全基因组关联研究 因果关系 

分 类 号：R735.7[医药卫生—肿瘤]