双样本孟德尔随机化分析肠道菌群与慢性阻塞性肺疾病急性加重风险的因果关系研究

Association of gut microbiota with acute exacerbation of chronic obstructive pulmonary disease:a two-sample Mendelian randomization analysis

目的探索肠道菌群与慢性阻塞性肺疾病急性加重之间的因果关系。方法双样本孟德尔随机化研究使用MiBioGen联盟和EBI的全基因组关联研究数据,选取与肠道菌群密切相关的SNPs作为工具变量,探索其与慢阻肺急性加重风险的因果关系。逆方差加权分析法作为主要分析方法,敏感性分析用于检验MR分析结果是否可靠。结果分析结果显示,毛螺旋菌NK4A136群的丰度增加与慢阻肺急性加重风险显著降低相关(OR=0.72,95%CI:0.57~0.93,P=0.01),而梭状芽孢杆菌1群丰度的增加则显著增加慢阻肺急性加重风险(OR=1.46,95%CI:1.07~2.01,P=0.02)。敏感性分析,包括MR Egger回归,显示没有多效性和异质性的证据。结论肠道菌群与慢阻肺急性加重风险之间存在因果联系,其中毛螺旋菌NK4A136的丰度升高对慢阻肺患者具有保护作用,梭状芽孢杆菌1群则增加了慢阻肺急性的加重风险,为肠道菌群调节在AECOPD的治疗中提供了新方向。

Objective To explore the potential relationship between gut microbiota and acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods The Mendelian randomization(MR)study used genome-wide association study(GWAS)data from MiBioGen Consortium and EBI.The researchers chose SNPs,which were closely related to the gut microbiota,as instrumental variables to explore the potential relationship between SNPs and acute exacerbations of COPD.The primary analysis method was inverse variance weighted(IVW)analysis,and sensitivity analysis was used to verify the reliability of the MR analysis results.Results The analysis showed that an increase in Lachnospiraceae NK4A136 group significantly reduced the risk of acute exacerbation of COPD(OR=0.72,95%CI:0.57~0.93,P=0.01),whereas an increase in Clostridiumsensustricto1 abundance significantly increased the risk of acute COPD exacerbation risk(OR=1.46,95%CI:1.07~2.01,P=0.02).Sensitivity analyses,including MR Egger regression,showed no evidence of pleiotropy and heterogeneity.Conclusion There is a causal relationship between intestinal flora and the risk of acute exacerbation of COPD,in which the increased abundance of Trichospirochium NK4A136 has a protective effect on COPD patients,and Clostridium 1 group increases the risk of acute exacerbation of COPD,providing a new direction for the regulation of intestinal flora in the treatment of AECOPD.