The Association Between Oral Microbiota and Chronic Obstructive Pulmonary Disease: An Integrated Study of Genetic Causal Inference and Bioinformatics Analysis

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. 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. Forward MR identified 43 taxa associated with COPD, primarily from genera such as Fusobacterium, Prevotella, and Streptococcus. Reverse MR detected 73 taxa affected by COPD, mainly involving Campylobacter_A, 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 and Endothelial cells during early stages of COPD and linked to immune dysregulation. Molecular docking revealed six candidate drugs with strong binding affinity to MPDZ. Our study provides insights for the development of personalized treatment strategies for COPD and offers preliminary candidate targets and drugs for future drug development.