The translational potential of the lung microbiome as a biomarker and a therapeutic target for chronic obstructive pulmonary disease

Abstract Chronic obstructive pulmonary disease (COPD) is a major chronic lung disease with a leading global morbidity and mortality. Emerging evidence suggests that the lung microbiome, the collection of the microorganisms in the lung, plays a crucial role in COPD pathogenesis. The lung microbiome alters in COPD during the acute exacerbations, associates with clinical phenotypes and inflammatory endotypes, and predicts treatment response, lung function decline and mortality, suggesting it could be a potential biomarker for COPD phenotyping, prognosis and personalized therapies. The lung microbiome produces metabolites that interact with host immunity and contribute to COPD pathogenesis, implying that it could be a possible novel target for therapeutic intervention. Despite these potentials, critical gaps exist for translational application of the lung microbiome in COPD clinical practice, starting with the lack of approaches in precisely measuring and manipulating specific members of the lung microbiome, highlighting the need for future collaborative efforts from bench to bedsides. In this perspective, we review existing knowledge and progress on the understanding of the lung microbiome as a possible COPD biomarker or a therapeutic target. We discuss current challenges and share our views on future directions toward fully realize the potential in translational application of the lung microbiome in the promise of COPD precision medicine.