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.
Authors
- Alise Jany Ponsero (ORCID: https://orcid.org/0000-0002-4125-7561)
- Andrea Telatin (ORCID: https://orcid.org/0000-0001-7619-281X)
- Yuqiong Yang (ORCID: https://orcid.org/0000-0002-6907-592X)
- Andrew Millard (ORCID: https://orcid.org/0000-0002-3895-2854)
- Ryan Cook
- Martha R. J. Clokie (ORCID: https://orcid.org/0000-0002-6069-8936)
- Zhenyu Liang (ORCID: https://orcid.org/0000-0002-8746-315X)
- Christopher Edward Brightling (ORCID: https://orcid.org/0000-0002-9345-4903)
- Evelien M. Adriaenssens (ORCID: https://orcid.org/0000-0003-4826-5406)
- Fengyan Wang (ORCID: https://orcid.org/0000-0001-5737-0625)
- Zhang Wang (ORCID: https://orcid.org/0000-0003-1278-8950)
- Rongchang Chen (ORCID: https://orcid.org/0000-0001-7050-7876)
Institutions
- University of Leicester (GB)
- South China Normal University (CN)
- Norwich Research Park (GB)
- Quadram Institute (GB)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- State Key Laboratory of Respiratory Disease (CN)
- NIHR Leicester Biomedical Research Centre (GB)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116413
- Citations
- 1
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 1.72
Funders
- National Institute for Health and Care Research
- Department of Health and Social Care
- National Natural Science Foundation of China
- National Science and Technology Major Project
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- NIHR Leicester Biomedical Research Centre
- NIHR Leicester Clinical Research Facility