Bacteriophage diversity declines with COPD severity in the respiratory microbiome

Chronic obstructive pulmonary disease (COPD) severity correlates with airway microbial dysbiosis, yet bacteriophage roles remain unexplored. We characterized the lung DNA virome by re-analyzing 135 sputum metagenomes from 99 COPD patients and 36 healthy controls. We identified 1,308 viral operational taxonomic units, revealing progressively lower viral diversity correlating with disease severity. While viral and bacterial diversity typically showed strong positive correlations, patients with frequent exacerbations uniquely exhibited decoupled viral-bacterial relationships, indicating disrupted ecological dynamics. Comparing all COPD patients to controls, phages infecting anaerobic oral bacteria showed disproportionately lower abundance-Porphyromonas phages were 40-fold less abundant, despite only 4-fold lower bacterial abundance-while pathogen-associated phages showed no significant differences. We detected virulence factor-encoding phages, including two neuA-carrying Haemophilus phages in 7.4% of Haemophilus-colonized patients, associated with 82-fold higher bacterial abundance. These findings establish altered bacteriophage ecology as an unrecognized feature of COPD pathobiology, with differential phage-bacteria relationships that reshape lung microbial ecosystems, offering new perspectives for microbiome-targeted interventions.