孟德尔随机化分析肠道菌群与系统性硬皮病的因果关系  

Analyze the causal relationship between gut microbiota and systemic sclerosis and pathogenic bacteria based using Mendelian randomization

作　　者：徐经纬 韩立[2] 郭克磊 孟庆良 卞华 XU Jingwei;HAN Li;GUO Kelei;MENG Qingliang;BIAN Hua(Department of Rheumatology,College of Bone Injury,Henan University of Traditional Chinese Medicine,Zhengzhou 450000,Henan Province,China;不详)

机构地区：[1]河南中医药大学骨伤学院风湿病科,河南郑州450000 [2]南阳理工学院河南省张仲景方药与免疫调节重点实验室,河南南阳473004

出　　处：《微生物学免疫学进展》2024年第3期52-58,共7页Progress In Microbiology and Immunology

基　　金：国家自然科学基金项目(82074415);中原科技创新领军人才项目(234200510006)。

摘　　要：目的利用孟德尔随机化(Mendelian randomization,MR)分析肠道菌群与系统性硬皮病(systemic sclerosis,SSc)之间的因果关系。方法获取肠道菌群和SSc的全基因组关联研究(genome-wide association study,GWAS)数据,筛选出强工具变量(instrumental variable,IV),以逆方差加权法(inverse-variance weighting,IVW)为主,MR-Egger、加权中位数法(weighted median estimate,WME)作为补充,评价因果效应。再使用Cochran Q检验、MR-PRESSO检验、MR-Egger截距检验和留一法分析评估结果的稳健性。最后,绘制工具变量相关的森林图、散点图及漏斗图等。结果MR分析共鉴定出4种肠道菌群(Collinsella属、RuminococcaceaeUCG003属、Subdoligranulum属和NB1n目),均与SSc的关联效应值差异具有统计学意义(P<0.05)。IVW:Collinsella属(OR:7.260;95%CI:1.595~33.057);RuminococcaceaeUCG003属(OR:5.046;95%CI:1.463~17.400);Subdoligranulum属(OR:0.150;95%CI:0.038~0.588);NB1n目(OR:0.389;95%CI:0.184~0.819);其余2种方法跟IVW法结果一致。Cochran Q检验显示不存在异质性,MR-PRESSO检验没有发现离群值,MR-Egger截距检验表明结果不存在水平多效性,留一法分析支持结果的稳健性。结论MR分析结果支持肠道菌群和SSc存在潜在的因果关系,Collinsella属和RuminococcaceaeUCG003属与SSc发病风险呈正相关,Subdoligranulum属和NB1n目与SSc发病风险呈负相关,需要更多的研究来揭示肠道菌群如何影响SSc发病。Objective Analysis of the causal relationship between intestinal flora and systemic sclerosis(SSc)using Mendelian randomization(MR).Methods We obtained genome-wide association study(GWAS)data of GI flora and SSc,screened out strong instrumental variables(instrumental variable,IV)and evaluated the causal effect by inverse-variance weighting(IVW),supplemented by MR-Egger and weighted median estimate(WME).Then,using Cochran's Q test,MRPRESSO test,MR-Egger intercept test and leave-one-out method to evaluate robustness of results.Finally,forest plots,scatter plots and funnel plots related to instrumental variables were drawn.Results A total of 4 bacterial taxa were identified exhibit significant association with SSc(Collinsella genus,RuminococcaceaeUCG0033 genus,Subdoligranulum genus and NBln order)(all P<0.05).IVW:Collinsella genus(OR:7.260;95%CI:1.595-33.057),RuminococcaceaeUCG003 genus(OR:5.046;95%CI:1.463-17.400),Subdoligranulum genus(OR:0.150;95%CI:0.038-0.588);order NBIn(OR:0.389;95%CI:0.184-0.819).The results of the other two methods were consistent with IVW.Cochran Q test showed no heterogeneity,MR-PRESSO test did not find outliers,the MR-Egger intercept test showed that the results were not horizontally multivariat,and leave-one-out analysis supported robustness of the results.Conclusion The results of MR analysis supported the existence of potential causal relationship between gut microbiota and SSc.Collinsella and RuminococcaceaeUCGO03 genus were positively correlated with the risk of SSc,while Subdoligranulum genus and the order NBln were negatively correlated with the risk of SSc.More research is needed to reveal how gut microbiota influences the pathogenesis of SSc.

关 键 词：肠道菌群 系统性硬皮病 孟德尔随机化 因果关系 单核苷酸多态性 逆方差加权法 

分 类 号：R392[医药卫生—免疫学]