This establishes bacteriophages, which are viruses that infect bacteria, as an unrecognised but potentially important component of the condition, according to a new study from the Quadram Institute, Becky Mayer Centre for Phage Research and Guangzhou Institute of Respiratory Health.

Chronic obstructive pulmonary disease (COPD) encompasses various conditions causing shortness of breath, a persistent cough, wheezing and susceptibility to chest infections. It leads to permanent lung damage and has no known cure. Treatments can slow progression, but flare-ups, or exacerbations, are a characteristic feature. COPD is now a leading cause of mortality worldwide.

The main causes of COPD are smoking or exposure to other harmful substances that trigger inflammation that damages the lining of the airways.

Our airways are lined with a dynamic community of microbes known collectively as the lung microbiome and changes in its composition have been linked to the development and progression of respiratory conditions, including COPD.

But these studies have focused on the bacteria, and not the viruses that coexist in those communities.

“In every environment where bacterial communities have been studied in detail, from the human gut to the ocean, the viruses also turn out to be important” said Dr Ryan Cook from the Quadram Institute.

The viral component of a microbiome plays a role in shaping the overall ecology of community. Bacteriophages infect specific bacteria, using them to replicate themselves. So a boom in one bacterial species may also boost the number of phages that predate on it, naturally rebalancing the microbiome.

Now, in research published in the journal Cell Reports, an important role for bacteriophages has been uncovered in the ecology of the lung microbiome linked to disease severity in COPD. Funding for this work came from the Biotechnology and Biological Sciences Research Council, part of UKRI.

Dr Ryan Cook and colleagues from the Quadram Institute and University of Leicester worked with scientists in China who had previously analysed microbiome samples from lining of airways of people with COPD. A disruption in the bacterial community is linked to the progression of the condition, exacerbations in symptoms and how patients respond to therapies. But to date the viral component has not been looked at.

The team reanalysed microbiome data from 99 COPD patients at different stages of severity of COPD and 36 healthy people as a comparison, but using state-of-the-art bioinformatic focused on viral DNA.

They found that as disease symptoms worsened, the diversity of the viruses present also dropped. In people with the most severe COPD, the viral diversity was the lowest by far. Viral diversity indicates a complex microbial community, which is usually linked to optimum health, so viral diversity could be an unseen biomarker for COPD progression.

Mostly, viral diversity correlated with bacterial diversity; as one dropped with worsening symptoms, so did the other.

However, in patients showing frequent exacerbations of the condition, there was a breakdown of the link between viral and bacterial diversity. This fundamental change in the microbiome ecology in this high-risk group of COPD patients may provide insights into the disease and has implications for the design of therapies that target the microbiome.

As well shaping bacterial populations through predation, bacteriophages have another trick that can alter the dynamics of a microbiome.

Certain groups of bacteriophages can integrate their genomes into those of host bacteria. In this state, where they are known as prophages, they may express viral genes that alter the behaviour of the bacteria. Cholera and botulism, for example, are caused by bacteria harbouring prophages capable of producing deadly toxins.

The team detected prophage DNA that potentially enhances the virulence of Haemophilus influenzae bacteria in a small number of patients. Haemophilus influenzae is known to be an important bacterial pathogen in COPD.

In this study, of the samples that contained Haemophilus influenzae, 7.4% were found to contain a virulence factor-encoding prophage that was associated with 82 times higher abundance of Haemophilus influenzae compared with samples lacking the prophage.

“We think this is the first time virulence factor-encoding bacteriophages have been linked to pathogen expansion in the human respiratory tract.” said Dr Ryan Cook. “The fact that they are associated with this dramatic increase in the abundance of Haemophilus influenzae is significant as it’s known that these bacteria can cause infections and further problems in some COPD patients.”

Although this study establishes an important role for phages in shaping the lung microbiome in COPD patients, it cannot say whether these changes cause disease progression or are a result of changes caused by the disease, or its treatments. Antibiotics used to treat COPD-related infections will massively disrupt the microbiome.

But these findings highlight why considering the viral as well as bacterial communities is important to fully understand respiratory dysbiosis and that potential therapies that target the microbiome should account for the viral component of the lung ecosystem.

Reference: Bacteriophage diversity declines with COPD severity in the respiratory microbiome, Ryan A. Cook, Alise J. Ponsero, Andrea Telatin, Yuqiong Yang, Zhenyu Liang, Fengyan Wang, Rongchang Chen, Zhang Wang, Evelien M. Adriaenssens, Martha R.J. Clokie, Andrew D. Millard, Christopher E. Brightling, Cell Reports, DOI: 10.1016/j.celrep.2025.116413