Circulating cytokines mediate the risk of COPD: A mediation analysis based on 473 gut microbiota and 91 circulating cytokines

In recent years, the roles of gut microbiota and circulating cytokines in chronic obstructive pulmonary disease (COPD) have gradually attracted attention. However, it remains unclear whether cytokines act as mediators from gut microbiota to COPD. This study utilized the mediation Mendelian randomization analysis method to explore the potential causal effects of gut microbiota and cytokines on COPD and reveal the potential mechanistic connections between them. We aggregated data from large-scale genome-wide association studies. Inverse variance weighted was used as the primary statistical method, and a series of sensitivity analyses were conducted to test the reliability of the Mendelian randomization results. We identified 24 gut microbiota species that show robust associations with COPD risk, with results supported by sensitivity analyses. Specifically, 11 gut microbiota species may increase the risk of COPD, while the remaining 13 species have a protective effect. Additionally, we observed associations between 7 circulating cytokines and COPD risk, among which 6 may increase the disease risk and 1 may reduce the disease risk. Mediation analysis revealed the complex regulatory roles of 4 key cytokines (LIF, IL-1A, CXCL10, CD6) between gut microbiota and COPD. This study reveals that circulating cytokines can act as potential mediators between gut microbiota and COPD. These findings not only deepen our understanding of the pathophysiological mechanisms of COPD but also provide new perspectives for the early intervention and treatment of COPD.