【摘要】 [目的]基于肺与大肠相表里理论，通过孟德尔随机化（Mendelian randomization, MR）方法分析肠道菌群和百日咳之间的因果关联。[方法]从MiBioGen数据库下载包含18 340名受试者的肠道菌群全基因组关联分析（genome-wide association analysis,GWAS）数据集，保留119种已知菌属作为暴露因素，以单核苷酸多态性（single nucleotide polymorphism, SNP）为工具变量。从FinnGen R10数据库下载包含169例患者的百日咳GWAS数据集用作结局变量。分别使用逆方差加权法、加权中位数法、MR-Egger、加权模式和简单模式方法进行MR分析，其中逆方差加权法为主要方法。利用Cochran Q检测异质性，使用MR-Egger和MR-PRESSO检验水平多效性，同时采用留一法进行敏感性分析。[结果]通过筛选共获得1 531个有效的工具变量，逆方差加权法结果显示，5个菌属与百日咳风险存在潜在因果关联，Fusicatenibacter[比值比（odd ratia,OR）=3.738]为风险因素，而Allisonella(OR=0.526)、Eubacterium brachy group(OR=0.525)、Clostridium sensu stricto 1(OR=0.306)和Ruminococcus torques group(OR=0.203)为保护因素。多种MR方法结果方向一致，且敏感性分析未发现明显的异质性、多效性。[结论] Fusicatenibacter与百日咳发生风险呈正相关，Allisonella、Eubacterium brachy group、Clostridium sensu stricto 1及Ruminococcus torques group与百日咳发生风险呈负相关，调节肠道菌群组成可能有助于百日咳的预防和干预。更多还原

【Abstract】 [Objective] Based on the theory of the exterior-interior relationship between the lung and the large intestine, to analyze the causal relationship between the gut microbiota and whooping cough by using the Mendelian randomization(MR) method. [Methods] A data set from the MiBioGen database comprising genome-wide association analysis(GWAS) data for 18 340 participants was downloaded, focusing on 119 known genera as exposure factors, with single nucleotide polymorphism(SNP) serving as instrumental variables. A whooping cough GWAS data set comprising 169 cases was sourced from the FinnGen R10 database to serve as the outcome variable. MR analysis was conducted by using several methods including the inverse variance weighted(primary method), weighted median, MR-Egger, weighted mode and simple mode. Heterogeneity was assessed by using Cochran’s Q, and pleiotropy was tested by using MR-Egger and MR-PRESSO, with leave-one-out sensitivity analysis also being implemented. [Results] A total of 1 531 valid instrumental variables were retained for the MR analyses. The inverse-variance weighted(IVW) approach identified potential causal associations between five bacterial genera and the risk of pertussis. Fusicatenibacter [odd ratio(OR)=3.738] emerged as a risk factor, whereas Allisonella(OR=0.526), the Eubacterium brachy group(OR=0.525), Clostridium sensu stricto 1(OR=0.306) and the Ruminococcus torques group(OR=0.203) were protective. Results were directionally consistent across multiple MR methods, and sensitivity analyses revealed no appreciable heterogeneity or horizontal pleiotropy. [Conclusion] Fusicatenibacter was positively associated with an increased risk of pertussis, whereas Allisonella, Eubacterium brachy group, Clostridium sensu stricto 1 and Ruminococcus torques group were inversely associated with pertussis risk. These findings suggested that modulating the composition of the gut microbiota may hold potential for the prevention and intervention of whooping cough.更多还原