Oral commensals are key mediators of shared airway host–microbe interactions in lung cancer and chronic obstructive pulmonary disease

Abstract Increased abundance of oral commensals in the lung microbiome affects survival and host gene expression in lung cancer. However, the interactions between host genes and microbes in lung diseases remain largely unknown. In this study, we applied topological network-based analysis to lung cancer and Chronic Obstructive Pulmonary Disease (COPD) using airway microbiome and host transcriptome data to identify key taxa and potential host-microbe interactions associated with these lung diseases. We show that while key driver species, identified as essential for community structure and function, differ between metagenomic and metatranscriptomic data, a common signature at both omic levels is the presence of oral commensals. By integrating existing human genetic and genomic findings, we identified shared host-microbe interactions relevant to lung cancer and COPD, including immune- and cancer-related genes and their interactions with both opportunistic pathogens and oral commensals. This study fills a critical gap in our understanding of the shared host–microbe interactions underlying lung cancer and COPD, providing a more integrated framework for investigating their common mechanisms.