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

Zhiyan Luo,1,2,&ast; Gang Liao,1,3,4,&ast; Miaodi Meng,2,&ast; Xiufang Huang,5 Xiaohong Liu,6 Wujin Wen,1 Tiegang Yue,1 Weifeng Yu,1 Changjun Wang,3,4 Yong Jiang1 1Department of Respiratory and Critical Care Medicine, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, People’s Republic of China; 2The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 4Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 5Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changjun Wang, Email [email protected] Yong Jiang, Email [email protected]: 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.Keywords: chronic obstructive pulmonary disease, gut microbiota, skin microbiota, Mendelian randomization