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

Wen-Jia Li,1,* Chen Yao,2,* Lu Han,1 Ji-Hong Zhou,1 Rui-Ming Pang2 1Department of Pulmonary and Critical Care Medicine, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People’s Republic of China; 2Department of Orthopedics and Traumatology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ji-Hong Zhou, Department of Pulmonary and Critical Care Medicine, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People’s Republic of China, Email [email protected] Rui-Ming Pang, Department of Orthopedics and Traumatology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People’s Republic of China, Email [email protected]: The associations between gut microbiota and chronic obstructive pulmonary disease (COPD) have gained increasing attention and research interest among scholars. However, it remains unclear whether gut microbiota serves as a causal factor for COPD or if it is a consequence of the disease. Therefore, we investigated the causal relationship between COPD and gut microbiota, with intention of providing novel insights and references for clinical diagnosis and treatment.Methods: Based on the genome-wide association study (GWAS) data, we employed MR-Egger regression, random-effects inverse variance-weighted (IVW) method, and weighted median method for bidirectional Mendelian randomization (MR) analysis. We conducted Cochran’s Q test for heterogeneity assessment and performed multivariable analysis, sensitivity analysis, and heterogeneity testing to validate the reliability and stability of results.Results: Utilizing MR analysis, mainly employing the IVW method, we detected a collective of 11 gut microbiota species that exhibited associations with COPD. Among them, Bacteroidia, family XIII, Clostridium innocuum group, Barnesiella, Collinsella, Lachnospiraceae NK4A136 group, Lachnospiraceae UCG004, Lachnospiraceae UCG010, and Bacteroidales were found to be protective factors for COPD. On the other hand, Holdemanella and Marvinbryantia were identified as risk factors for COPD. Individuals with elevated levels of Holdemanella exhibited a 1.141-fold higher risk of developing COPD compared to their healthy counterparts, and those with increased levels of Marvinbryantia had a 1.154-fold higher risk. Reverse MR analysis yielded no evidence indicating a causal relationship between gut microbiota and COPD occurrence.Conclusion: Our study established a causal link between 11 specific gut microbiota species and COPD, offering novel insights and valuable references for targeted therapies in the clinical management of COPD. However, our results were mainly based on the analysis of database, and further clinical studies are needed to clarify the effects of gut microbiota on COPD and its specific protective mechanism.Keywords: gut microbiota, COPD, bidirectional MR, causal, association