两样本双向孟德尔随机化分析肠道微生物与脓毒症的因果关系

Two-sample bidirectional Mendelian randomization analysis of the causal relationship between gut microbiota and sepsis

目的采用双向孟德尔随机化(MR)方法,探讨211种肠道微生物与脓毒症之间的因果关系.方法利用微生物基因组多中心联盟(MiBioGen)肠道微生物基于全基因组关联研究(GWAS,n=18340)数据和芬兰数据库中脓毒症GWAS数据(n=286146).首先,根据预设条件筛选出与211个肠道微生物类群相对丰度显著相关的单核苷酸多态性(SNP)作为工具变量.主要的分析方法采用逆方差加权法,并使用效应指标优势比(OR)来评估MR结果.为验证结果的准确性、可靠性进行了留一法、异质性检验以及相干和不相干水平基因多效性检验.结果柯林斯菌属[Collinsella,OR=1.28,95%可信区间(95%CI)为1.06~1.56,P=0.01]、瘤胃球菌属(Ruminococcus,OR=1.19,95%CI为1.05~1.35,P=0.005)丰度升高会增加脓毒症的患病风险;普雷沃菌属(Prevotella,OR=0.88,95%CI为0.79~0.97,P=0.01)、厚壁菌门(Firmicutes,OR=0.86,95%CI为0.75~0.996,P=0.04)的丰度升高对脓毒症发病有保护作用,并且未发现明显的异质性和不相干水平多效性.结论Collinsella、Ruminococcus会增加脓毒症的发生风险,Prevotella、Firmicutes对脓毒症的发生有保护作用.

Objective To delve into the causal relationship between 21l gut microbiota and sepsis employing bidirectional Mendelian randomization(MR).Methods The gut microbiota genome-wide association study(CWAS)data from the Microbiome Genetics Consortium(MiBioGen,n=18340)and sepsis GWAS data from the FinnGen(n=286146)were harnessed for this study.Initially,single nucleotide polymorphisms(SNP)significantly associated with the relative abundance of 21l gut microbiota taxa were identified as instrumental variables using predefined selection criteria.The primary analytical approach was characterized by the application of inverse variance weighting(IVW),with the effect measure represented by the odds ratio(OR)to assess the results of MR.To ensure precision and reliability.analyses were conducted,including leave-one-out analysis,heterogeneity testing,and tests for pleiotropy at both coherent and incoherent levels.Results The increased risk of sepsis was associated with the elevated abundance of Collinsella[OR=1.28,95%confidence interval(95%CD)was 1.06-1.56,P=0.01]and Ruminococcus(OR=1.19.95%CI was 1.05-1.35,P=0.005).Furthermore,a protective effect against the development of sepsis was observed in association with the increased abundance of Prevotella(OR=0.88,95%CI was 0.79-0.97,P=0.01)and Firmicutes(OR=0.86,95%CI was 0.75-0.996,P=0.04).No obvious heterogeneity and irrelevant level pleiotropy were detected.Conclusion Collinsella and Ruminococcus increase the risk of sepsis,while Prevotella and Firmicutes have protective effects against sepsis.