Gao Yaning, Chen Liang, Zhang Jianhong, Wen Zhengjun
Respiratory and Critical Care Medicine Department, Beijing Jingmei Group General Hospital, Beijing, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2025 Jul 3;20:2173-2182. doi: 10.2147/COPD.S518455. eCollection 2025.
The gut-lung axis, representing the communication between gut microbiota and the lungs, has been hypothesized to influence chronic obstructive pulmonary disease (COPD) development through modulation of the immune response. However, the causal role of gut microbiota in COPD and the potential mediating role of immune cells remain largely undetermined. This study aimed to uncover the causal relationship between gut microbiota and COPD and explore the potential mediating role of immune cells in this connection.
This study employed a two-step Mendelian randomization (MR) analysis to investigate the causal effect of gut microbiota on COPD and explore the potential mediating role of immune cells in this relationship. The inverse variance weighted method served as the primary MR analysis method.
MR analyses revealed statistically significant genetic associations between 28 gut microbiota and COPD. Among these, the genus demonstrated the strongest causal effect on COPD risk, exhibiting a significant positive association (odds ratio (OR) = 1.18, 95% confidence interval (CI): 1.03-1.36, = 0.03). Additionally, 15 immune cell traits displayed significant associations with . Notably, CD27 expressed on IgD CD38 B cells emerged as a potential contributor to COPD development (OR = 1.04, 95% CI: 1.00-1.07, = 0.03). We further explored the potential mediating effect of CD27 on IgD CD38 B cells in the relationship between and COPD.
Our MR analysis provided evidence for a causal association between gut microbiota and COPD, potentially mediated by immune cells.
肠-肺轴代表肠道微生物群与肺之间的通讯，据推测其可通过调节免疫反应影响慢性阻塞性肺疾病（COPD）的发展。然而，肠道微生物群在COPD中的因果作用以及免疫细胞的潜在中介作用在很大程度上仍未确定。本研究旨在揭示肠道微生物群与COPD之间的因果关系，并探讨免疫细胞在这一关系中的潜在中介作用。
本研究采用两步孟德尔随机化（MR）分析来研究肠道微生物群对COPD的因果效应，并探讨免疫细胞在这种关系中的潜在中介作用。逆方差加权法作为主要的MR分析方法。
MR分析揭示了28种肠道微生物群与COPD之间具有统计学意义的遗传关联。其中，该属对COPD风险的因果效应最强，呈现出显著的正相关（比值比（OR）=1.18，95%置信区间（CI）：1.03-1.36，P=0.03）。此外，15种免疫细胞特征与该属有显著关联。值得注意的是，IgD CD38 B细胞上表达的CD27成为COPD发展的一个潜在因素（OR = 1.04，95% CI：1.00-1.07，P = 0.03）。我们进一步探讨了CD27在该属与COPD关系中对IgD CD38 B细胞的潜在中介作用。
我们的MR分析为肠道微生物群与COPD之间的因果关联提供了证据，可能由免疫细胞介导。
