Zhu Hongyu, Chen Caihua, Guo Haixie, Zhang Bo, Hu Quanteng
Department of Thoracic Surgery, Taizhou Hospital, Taizhou, Zhejiang, China.
Clin Respir J. 2025 Sep;19(9):e70120. doi: 10.1111/crj.70120.
Persistent inflammation is a crucial characteristic of idiopathic pulmonary fibrosis (IPF). Gut microbiota (GM) contribute to the occurrence and development of several pulmonary diseases through the "gut-lung axis." The genetic role of GM in IPF and the mediating effect of circulating inflammatory proteins.
A single nucleotide polymorphism (SNP) was used as an instrumental variable (IV) for exposure to evaluate the causal relationship between exposure and outcome. A two-step, two-sample Mendelian randomization study mainly based on an "inverse variance weighted (IVW)" approach was performed to explore the causal relationship between GM and IPF mediated by circulating inflammatory proteins.
The IVW way illustrated 12 taxa (Bacillales, Gastranaerophilales, Selenomonadales, Family XIII, Bacteroidaceae, Bacteroides, and Actinomyces, Bifidobacterium, Oscillibacter, Ruminococcus gnavus, Subdoligranulum, Veillonella) of GM and 8 circulating inflammatory proteins (CCL11, CXCL6, CXCL9, CCL8, CCL7, NRTN, STAMPB, and TGFa) had suggestive evidence of causality on IPF. The mediation MR demonstrated the causal pathway from Actinomyces to IPF was partly mediated by CCL11 (the mediation effect: 0.063, 95% CI [1.016-1.126]; p = 0.004) with a mediation proportion of 13.035%.
These findings may suggest a genetically predicted association between GM and IPF mediated by circulating inflammatory proteins.
持续性炎症是特发性肺纤维化（IPF）的关键特征。肠道微生物群（GM）通过“肠-肺轴”促进多种肺部疾病的发生和发展。GM在IPF中的遗传作用以及循环炎症蛋白的介导作用。
使用单核苷酸多态性（SNP）作为暴露的工具变量（IV）来评估暴露与结局之间的因果关系。进行了一项主要基于“逆方差加权（IVW）”方法的两步两样本孟德尔随机化研究，以探讨GM与由循环炎症蛋白介导的IPF之间的因果关系。
IVW方法表明，GM的12个分类群（芽孢杆菌目、嗜气厌氧杆菌目、月形单胞菌目、第十三科、拟杆菌科、拟杆菌属、放线菌属、双歧杆菌属、颤杆菌属、纤细瘤胃球菌、副拟杆菌属、韦荣球菌属）和8种循环炎症蛋白（CCL11、CXCL6、CXCL9、CCL8、CCL7、神经营养因子、STAMPB和转化生长因子α）对IPF具有因果关系的提示性证据。中介MR表明，从放线菌到IPF的因果途径部分由CCL11介导（中介效应：0.063，95%CI[1.016-1.126]；p=0.004），中介比例为13.035%。
这些发现可能提示GM与由循环炎症蛋白介导的IPF之间存在遗传预测的关联。
