Genetic analysis links oral microbiota to COPD risk in East Asian population

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of global mortality. Emerging evidence suggests the oral microbiome may contribute to COPD progression, though causal relationships remain elusive. Methods: Using bidirectional Mendelian randomization (MR) on East Asian genome-wide association study (GWAS) summary data, we assessed causal links between oral microbial taxa and COPD risk. Subsequently, hub genes in COPD bulk RNA sequencing data were identified by integrating the Protein-Protein Interaction (PPI) network with machine learning, followed by target validation using single-cell RNA sequencing, immune infiltration analysis, and molecular docking. Results: Forward MR identified 48 taxa associated with COPD, primarily from genera such as Fusobacterium, Prevotella, and Streptococcus. Reverse MR detected 79 taxa affected by COPD, mainly involving Campylobacter, Rothia, and Streptococcus. Through the PPI network, machine learning screening, and multi-omics analysis validation, MPDZ emerged as a key hub gene, upregulated in Ciliated cells and linked to immune dysregulation. Molecular docking revealed six candidate drugs with strong binding affinity to MPDZ. Conclusion: Our study provides insights for the development of personalized treatment strategies for COPD and offers preliminary candidate targets and drugs for future drug development.