肠道微生物与细菌性肺炎易感性的因果关系:双样本双向孟德尔随机化研究及cML-MA的应用

The causal relationship between gut microbiota and bacterial pneumonia:A two-sample bidirectional mendelian randomization study and application of cML-MA

目的通过孟德尔随机化研究方法探究肠道菌群与细菌性肺炎易感性之间的因果关系。方法使用三种不同的孟德尔随机化分析方法,对211个肠道菌群类群与细菌性肺炎之间的关系进行211次双样本分析,并进行反向孟德尔随机化分析。以随机效应逆方差加权法(IVW)作为主要结果,并采用其他方法作为补充参考。结果柔膜菌纲(OR=1.14,95%CI 1.02~1.27,P=0.02)、放线菌科(OR=1.17,95%CI 1.02~1.35,P=0.03)、放线菌目(OR=1.17,95%CI 1.01~1.35,P=0.03)以及软壁菌门(OR=1.14,95%CI 1.02~1.27,P=0.02)的丰度升高与细菌性肺炎易感性的增加有关;消化球菌科(OR=0.88,95%CI 0.78~0.98,P=0.02)、直肠拟梭菌群(OR=0.85,95%CI 0.75~0.97,P=0.02)和鞘螺菌科UCG001(OR=0.90,95%CI 0.83~0.99,P=0.03)的丰度升高与细菌性肺炎的发病风险降低相关。一系列敏感性分析以及条件孟德尔随机化分析(cML-MA)的结果表示该研究结果可靠。反向孟德尔随机化未发现反向因果关联。结论肠道微生物的丰度升高与细菌性肺炎的易感性增加或降低相关,肠道菌群在细菌性肺炎发病机制中有重要作用,提供了潜在干预措施的新思路。

Objective To investigate the causal relationship between gut microbiota and susceptibility to bacterial pneumonia by using Mendelian randomization(MR)study.Methods Three different Mendian randomization analysis methods were employed in this study to analyze the relationship between 211 gut microbiota taxa and bacterial pneumonia in 211 paired samples,followed by reverse Mendian randomization analysis.The inverse variance weighting(IVW)method was used as the main outcome,with other methods serving as supplementary references.Results The study revealed that increased abundance of Mollicutes(OR=1.14,95%CI 1.02-1.27,P=0.02),Actinomycetaceae(OR=1.17,95%CI 1.02-1.35,P=0.03),Actinomycetales(OR=1.17,95%CI 1.01-1.35,P=0.03),and Tenericutes(OR=1.14,95%CI 1.02-1.27,P=0.02)was associated with increased susceptibility to bacterial pneumonia.Furthermore,increased abundance of Peptococcaceae(OR=0.88,95%CI 0.78-0.98,P=0.02),Eubacteriumrectalegroup(OR=0.85,95%CI 0.75-0.97,P=0.02),and Lachnospiraceae UCG001(OR=0.90,95%CI 0.83-0.99,P=0.03)was associated with a decreased risk of bacterial pneumonia.Sensitivity analysis and cML-MA results supported the reliability of the study findings.Reverse Mendelian randomization did not find reverse causality.Conclusions The results of this study demonstrate a correlation between increased abundance of certain gut microbial taxa and increased or decreased susceptibility to bacterial pneumonia.This gut microbiota plays an important role in the pathogenesis of bacterial pneumonia.The article provides novel insights for future researches and potential intervention strategies.