摘要
目的:评估肠道菌群与非结核分枝杆菌肺感染(non-tuberculous mycobacteria lung infection,NTM-LI)之间的因果方向。方法:采用两样本双向孟德尔随机化(Mendelian randomization,MR)分析。肠道菌群与NTM-LI的全基因组关联研究汇总数据分别来自GWAS Catalog和芬兰数据库。工具变量筛选基于全基因组显著性、连锁不平衡分析和弱工具变量检验。主要使用逆方差加权法(IVW)评估因果效应,辅以MR-Egger、加权中位数、简单众数和加权众数法验证。通过Cochran Q、留一法、MR-Egger截距检验和MR-PRESSO评估异质性、敏感性和水平多效性。反向MR分析采用相同流程。结果:IVW分析显示,特定肠道菌群丰度变化与NTM-LI发病风险明显相关。其中,羊毛状臭气杆菌(OR=1.798,95%CI:1.017~3.180,P=0.044)、懒惰脱硫弧菌(OR=1.508,95%CI:1.069~2.128,P=0.019)及汉氏布劳特氏菌(OR=2.487,95%CI:1.222~5.062,P=0.012)被识别为风险因子。相反,苏黎世杆菌科(OR=0.570,95%CI:0.343~0.949,P=0.031)、RUG420 sp900317985(OR=0.153,95%CI:0.036~0.649,P=0.011)、厚壁菌门E(OR=0.084,95%CI:0.009~0.814,P=0.033)、人肠道杆菌属(OR=0.386,95%CI:0.197~0.756,P=0.006)和CAG-145 sp000435615(OR=0.575,95%CI:0.357~0.927,P=0.023)表现出保护效应。未发现明显异质性、水平多效性或离群值干扰。反向MR未支持NTM-LI对菌群的反向因果。结论:本研究通过MR揭示特定肠道菌群与NTM-LI之间存在一定的因果关系,靶向调控这些菌群或为NTM-LI防治提供新策略。
Objective:To assess the causal direction between gut microbiota and non-tuberculous mycobacteria lung infection(NTM-LI).Methods:This study used a bidirectional two-sample Mendelian randomization(MR).Genome-wide association studies(GWAS)data of gut microbiota and NTM-LI were obtained from the GWAS Catalog and the FinnGen databases,respectively.Instrumental variables(IV)were selected based on genome-wide significance thresholds,linkage disequilibrium analysis,and weak instrumental variable screening.The primary causal effect assessed using the inverse-variance weighted(IVW)method,supplemented by using MR-Egger,weighted median,simple mode,and weighted mode methods.Heterogeneity,sensitivity,and horizontal pleiotropy were evaluated using Cochran’s Q test,leave-one-out analysis,MR-Egger intercept test,and MR-PRESSO,respectively.Reverse MR analysis followed the same protocol.Results:IVW analysis revealed that changes in the abundance of specific gut microbiota taxa were significantly associated with the risk of NTM-LI.Odoribacter laneus(OR=1.798,95%CI:1.017-3.180,P=0.044),Desulfovibrio piger(OR=1.508,95%CI:1.069-2.128,P=0.019)and Blautia hansenii(OR=2.487,95%CI:1.222-5.062,P=0.012)could increase the risk of NTM-LI.Conversely,Turicibacteraceae(OR=0.570,95%CI:0.343-0.949,P=0.031),RUG420 sp900317985(OR=0.153,95%CI:0.036-0.649,P=0.011),Firmicutes E(OR=0.084,95%CI:0.009-0.814,P=0.033),Enteroscipio(OR=0.386,95%CI:0.197-0.756,P=0.006),and CAG-145 sp000435615(OR=0.575,95%CI:0.357-0.927,P=0.023)could reduce the risk of NTM-LI.No significant heterogeneity,horizontal pleiotropy,and outlier interference was detected.Furthermore,reverse MR analysis did not support effect of NTM-LI on gut microbiota composition.Conclusion:This MR analysis reveals a potential causal relationship between specific gut microbiota and NTM-LI.Targeted modulation of these specific gut microbial taxa holds promise as a novel intervention strategy for the prevention and treatment of NTM-LI.
作者
谭霄
李芳萍
张谦
张美家
Tan Xiao;Li Fangping;Zhang Qian;Zhang Meijia(Clinical Pharmacy Department,Weifang NO.2 People’s Hospital,Shandong Province,Weifang 261041,China;College of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China)
出处
《中国防痨杂志》
北大核心
2026年第1期121-130,共10页
Chinese Journal of Antituberculosis
基金
潍坊市卫生健康委科研项目(WFWSJK-2025-209)
潍坊市科技发展计划项目(2025YX065)。
关键词
肠道菌群
分枝杆菌感染
肺疾病
因果律
孟德尔随机化
Gut microbiota
Mycobacterium infections
Lung diseases
Causality
Mendelian randomization
