Hou Nianzong, Zhang Zhenhong, Song Weiwei, Wang Lin, Xu Guoxiang, Zhang Rumin, Yang Yulong, Wang Kai
Center of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, School of Medicine, Tongji University, Shanghai, China.
Center of Translational Medicine, Zibo Central Hospital, Binzhou Medical University, Zibo, Shandong, China.
J Cell Mol Med. 2025 Sep;29(17):e70839. doi: 10.1111/jcmm.70839.
The gut-lung axis plays a pivotal role in pneumonia pathogenesis, with immune regulation serving as a key mechanistic link between gut microbiota and disease progression. Despite established associations among gut microbiota, immune cell traits and pneumonia, their causal interplay and underlying mechanisms remain poorly elucidated. To investigate the causal relationships between gut microbiota and pneumonia and quantify the mediating effects of immune cell traits using Mendelian randomisation (MR), we performed a two-sample MR and multivariable MR (MVMR) analysis employing inverse-variance weighted (IVW) as the primary method. Genetic instruments for 211 gut microbiota taxa and 731 immune cell traits were derived from genome-wide association studies (GWAS). Mediation analysis was conducted to estimate immune cell-mediated effects on microbiota-pneumonia associations. Genetically predicted abundance of the Oxalobacteraceae family was positively associated with pneumonia risk (OR: 1.090; 95% CI: 1.010-1.175; p = 0.026). Mediation analysis revealed that CD16 monocytes significantly mediated this relationship (Mediated Effect: 0.025, proportion mediated: 29.1%). This study provides genetic evidence supporting Oxalobacteraceae as a causal risk factor for pneumonia, partially mediated through CD16 monocyte regulation. These findings offer novel insights into microbiome-directed immunomodulatory strategies for pneumonia prevention.
肠-肺轴在肺炎发病机制中起关键作用，免疫调节是肠道微生物群与疾病进展之间的关键机制联系。尽管肠道微生物群、免疫细胞特征与肺炎之间已建立关联，但其因果相互作用和潜在机制仍不清楚。为了研究肠道微生物群与肺炎之间的因果关系，并使用孟德尔随机化（MR）量化免疫细胞特征的中介作用，我们采用逆方差加权（IVW）作为主要方法进行了两样本MR和多变量MR（MVMR）分析。211种肠道微生物分类群和731种免疫细胞特征的遗传工具来自全基因组关联研究（GWAS）。进行中介分析以估计免疫细胞对微生物群-肺炎关联的介导作用。草酸杆菌科的遗传预测丰度与肺炎风险呈正相关（OR：1.090；95%CI：1.010-1.175；p = 0.026）。中介分析显示，CD16单核细胞显著介导了这种关系（介导效应：0.025，介导比例：29.1%）。本研究提供了遗传证据，支持草酸杆菌科作为肺炎的因果危险因素，部分通过CD16单核细胞调节介导。这些发现为肺炎预防的微生物群导向免疫调节策略提供了新见解。
