The Causal Relationship Between Gut and Skin Microbiota and Chronic Obstructive Pulmonary Disease:A Bidirectional Two-Sample Mendelian Randomization Analysis

Background: Recently, numerous studies have explored the potential impact of gut microbiota on Chronic Obstructive Pulmonary Disease (COPD). However, the causal relationship between skin microbiota and COPD, as well as the differences and similarities between the relationships of gut microbiota and COPD, has not been thoroughly studied. Methods: We conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the relationships between gut and skin microbiota and COPD. The inverse variance weighted (IVW) method was used as the primary approach. MR- Egger, weighted median, and MR-PRESSO methods were used as supplementary approaches. Various sensitivity and stability analyses were conducted to validate the results. Genetic variations of gut microbiota were obtained from the FR02 cohort study. Genetic variations of skin microbiota were derived from the KORA FF4 and PopGen cohorts, with a total of 1,656 skin samples. GWAS data for COPD were obtained from the FinnGen consortium, including 18,266 COPD cases and 311,286 controls from European cohorts. Results: The results of IVW method of MR analysis showed that 10 gut microbiotas and 4 skin microbiotas were negatively associated with COPD [p < 0.05, odds ratio (OR) < 1]; 3 gut microbiotas and 6 skin microbiotas were positively associated with COPD (p < 0.05, OR > 1). None of them were heterogeneous or horizontally pleiotropic (p > 0.05) or reverse causality. Conclusion: This study revealed the causal relationships between gut and skin microbiota and COPD, offering fresh perspectives for the prevention, diagnosis, and management of COPD.