基于孟德尔随机化分析肠道微生物群与哮喘的因果关系

The Causal Relationship between Gut Microbiota and Asthma Based on Mendelian Randomization

摘要: 目的：本研究旨在通过孟德尔随机化(Mendelian Randomization, MR)分析探讨肠道微生物群与哮喘之间的因果关系。方法：从MiBioGen数据库下载人类肠道微生物群数据集，包含18,340名参与者的遗传数据，保留196个细菌类群作为暴露因素。结局变量数据来自IEU OpenGWAS数据库，包含39,049例哮喘患者和298,110例对照。采用逆方差加权(Inverse Variance Weighted, IVW)、MR-Egger、简单模式(Simple Mode, SM)、加权中位数(Weighted Median, WM)和加权模式(Weighted Mode, WME)方法进行孟德尔随机化分析，其中IVW法作为主要分析方法。敏感性分析用于验证结果的可靠性。结果：IVW分析结果显示，Candidatus Soleaferrea属(OR = 1.009, 95% CI: 1.003~1.015, P = 0.002)、克里斯滕森菌科R-7群(OR = 1.019, 95% CI: 1.009~1.029, P < 0.001)、阿克曼氏菌(OR = 1.008, 95% CI: 1.000~1.016, P = 0.049)和毛螺菌属(OR = 1.027, 95% CI: 1.015~1.038, P < 0.001)与哮喘发病风险增加有关，而严格梭菌属1 (OR = 0.992, 95% CI: 0.984~1.000, P = 0.045)和双歧杆菌(OR = 0.989, 95% CI: 0.982~0.995, P < 0.001)与哮喘发病风险降低有关。此外，敏感性分析显示未发现异常SNPs。结论：本研究发现6种肠道微生物群与哮喘之间存在因果关系。Candidatus Soleaferrea属、克里斯滕森菌科R-7群、阿克曼氏菌和毛螺菌属与哮喘发病风险增加有关，而严格梭菌属1和双歧杆菌与哮喘发病风险降低有关。

Abstract: Objective: The aim of this study is to explore the causal relationship between intestinal microbiota and asthma through Mendelian Randomization (MR) analysis. Method: The human gut microbiota dataset, encompassing genetic data from 18,340 participants and including 196 bacterial taxa as exposure factors, was downloaded from the MiBioGen database. Outcome variable data were sourced from the IEU OpenGWAS database, comprising 39,049 asthma patients and 298,110 controls. Mendelian Randomization (MR) analysis was conducted using the Inverse Variance Weighted (IVW), MR-Egger, Simple Mode (SM), Weighted Median (WM), and Weighted Mode (WME) methods, with IVW serving as the primary analytical approach. Sensitivity analyses were performed to validate the reliability of the results. Results: The IVW analysis revealed that the genera Candidatus Soleaferrea (OR = 1.009, 95% CI: 1.003~1.015, P = 0.002), Christensenellaceae R-7 group (OR = 1.019, 95% CI: 1.009~1.029, P < 0.001), Akkermansia (OR = 1.008, 95% CI: 1.000~1.016, P = 0.049), and Lachnospira (OR = 1.027, 95% CI: 1.015~1.038, P < 0.001) were associated with an increased risk of asthma. In contrast, Clostridium sensu stricto 1 (OR = 0.992, 95% CI: 0.984~1.000, P = 0.045) and Bifidobacterium (OR = 0.989, 95% CI: 0.982~0.995, P < 0.001) were associated with a decreased risk of asthma. Sensitivity analysis did not identify any outlier SNPs. Conclusion: This study identified causal relationships between six gut microbiota and asthma. Specifically, the genera Candidatus Soleaferrea, Christensenellaceae R-7 group, Akkermansia, and Lachnospira were associated with an increased risk of asthma, whereas Clostridium sensu stricto 1 and Bifidobacterium were associated with a decreased risk of asthma.