肠道菌群介导睾酮对子宫内膜异位症影响的孟德尔随机化分析  

Mendelian randomization analysis of gut microbiota-mediated effects of testosterone on endometriosis

作　　者：李晓颖 马秀丽[1] 孙凌逸 李娜[1] 阙绮莹 吴晓婷 仇梦 LI Xiao-ying;MA Xiu-li;SUN Ling-yi;LI Na;QUE Qi-ying;WU Xiao-ting;QIU Meng(Obstetrics and Gynecology Department of Dongzhimen Hospital,Beijing University of Chinese Medicine,No.5,Dongcheng District,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院妇科,北京100700

出　　处：《现代预防医学》2024年第20期3816-3822,共7页Modern Preventive Medicine

基　　金：国家自然科学基金面上项目(81774360);北京中医药大学东直门医院2023科技创新专项(DZMKJCX-2023-006)。

摘　　要：目的基于孟德尔随机化分析探讨睾酮和子宫内膜异位症之间的因果关系,并确定和量化肠道菌群作为潜在介质的作用。方法使用IEUGWAS数据库中的睾酮(n=199569)和子宫内膜异位症(病例组8288例,对照组68969例)的汇总数据分别作为暴露和结局,MiBioGen联盟的肠道菌群汇总数据(n=18340)作为中介,进行双向、两步法孟德尔随机化分析。采用逆方差加权法、MR-Egger回归法、加权中位数法、加权模型法和简单模型法评估因果关系,敏感性分析检验结果是否稳健。结果逆方差加权法显示睾酮与子宫内膜异位症呈负向因果关系(OR=0.804,95%CI:0.670~0.964,P=0.018);反向孟德尔随机化显示,子宫内膜异位症对睾酮不呈现因果效应(OR=0.991,95%CI:0.958~1.026,P=0.616);肠道菌群中的黑色杆菌纲占睾酮(中介占比:17.21%,95%CI:0.090~0.264,P=0.035)相关的子宫内膜异位症风险降低的17.21%。结论睾酮是子宫内膜异位症的保护性因素之一,睾酮水平低会增加子宫内膜异位症的患病风险。肠道菌群可能是睾酮对子宫内膜异位症因果关系的中介因素。Objective To explore the causal relationship between testosterone and endometriosis,andto identify and quantify the role of gut microbiota as a potential mediator through Mendelian randomization analysis.Methods Utilizing the summary data from the IEU GWAS database for testosterone(n=199569)and endometriosis(8288 cases and 68969 controls)as the exposure and outcome variables,and the aggregated gut microbiota data from the MiBioGen Consortium(n=18340)as the mediator,a bidirectional,two-step Mendelian randomization analysis was conducted.Causal relationships were assessed using inverse varianceweighted,MR-Egger,weighted median,weighted model,and simple modelto assess causality,while sensitivity analysis was conducted to ensure the robustness of the findings.Results Impact of testosterone on endometriosis:Inverse variance weighted estimates suggested that testosterone had negative causal effects on endometriosis(OR=0.804,95%CI:0.670-0.964,P=0.018).Impact of endometriosis on testosterone:Reverse Mendelian randomization showed that endometriosis did not present a causal effect on testosterone(OR=0.991,95%CI:0.958-1.026,P=0.616).The class Melainabacteria,one of the gut microbiotas,accounted for a 17.21%reduction in the risk of endometriosis associated with testosterone(mediation proportion:17.21%,95%CI:0.090-0.264,P=0.035).Conclusion Testosterone is one of the protective factors of endometriosis.Low testosterone levels increase the risk of endometriosis.Gut microbiota may be a mediator of the causal effect of testosterone on endometriosis.

关 键 词：孟德尔随机化 子宫内膜异位症 睾酮 肠道菌群 因果推断 

分 类 号：R711.71[医药卫生—妇产科学]