Understanding the hidden communities in our lungs

Lung infections in people with cystic fibrosis can become persistent, severe and increasingly difficult to treat with antibiotics. Better understanding of why this happens is needed to help improve outcomes.

Why infections develop in cystic fibrosis

The human body is home to vast communities of bacteria, fungi and viruses, collectively known as the microbiome. Most of these microorganisms support essential functions, including digestion and immune regulation. However, in people living with certain respiratory conditions, changes within these microbial communities can contribute to infection and disease.

People with cystic fibrosis may experience stable periods followed by flare-ups of lung symptoms, when symptoms such as severe coughing, fever, increased mucus and difficulty breathing become significantly worse. Antibiotics can help people recover, showing that bacteria play an important role in these episodes. According to the Cystic Fibrosis Trust in 2024, 20% of people with cystic fibrosis in the UK had at least one course of intravenous antibiotics, underlining the continuing burden of lung infections. Repeated or long-term antibiotic treatment can increase the likelihood that bacteria will develop resistance.

Reducing the frequency and severity of these flare-ups could help people with cystic fibrosis live longer, healthier lives. For this to happen, researchers need to understand not only which bacteria are present in the lungs, but also how the interactions between them can cause these flare-ups.

Looking beyond individual bacteria

Respiratory infection research has traditionally focused on a small number of well-known pathogens, or harmful microbes or bacteria. While this has led to major advances in understanding and treating infection, the lungs contain many other microorganisms whose role remains less well understood.

The research led by Dr Fiona Whelan at The University of Manchester focuses on these understudied members of the microbial community and how they interact with established pathogens. Some microbes may work together in ways that make infections more severe by helping harmful bacteria survive or reduce the effectiveness of antibiotics.

By identifying these interactions, researchers hope to uncover opportunities to interfere with the relationships between bacteria. Rather than replacing the antibiotics already used to treat cystic fibrosis infections, future therapies could potentially be given alongside them to block harmful microbial interactions and make existing antibiotics more effective. Whilst the research remains at an early stage, improving understanding of the mechanisms behind these relationships could open the door to potentially new, more effective clinical therapies.

Combining microbiology and bioinformatics

A distinctive feature of the Manchester research is its combination of traditional laboratory microbiology with modern genomic and computational techniques.

Researchers grow bacteria and other microorganisms from phlegm samples provided by people with cystic fibrosis, then sequence their DNA and use bioinformatics to compare their genetic information.

This helps identify small but important differences between closely related bacteria. Two strains may appear almost identical, yet only one may interact with another microorganism in a way that worsens infection. Comparing their DNA can reveal the genes or biological mechanisms responsible.

While much microbiome research relies heavily on sequencing alone, growing microorganisms in the laboratory allows researchers to test how they behave and interact. Combining these approaches provides a fuller picture than either could offer independently.

Moving between the laboratory and the computer, the research brings together microbiology, genomics and data analysis to answer questions that could ultimately support more effective patient care.

Research shaped by patients and collaboration

The direction of the research has been strongly influenced by working closely with clinicians and meeting people living with cystic fibrosis.

Patient experiences continue to provide an important motivation for research across the cystic fibrosis community. In Manchester, this work contributes to PULSE-CF, a collaborative research hub led by Professor Alex Horsley and supported by the Cystic Fibrosis Trust and LifeArc.

The hub brings together clinicians, microbiologists, immunologists, biological scientists and people affected by cystic fibrosis. By sharing knowledge across disciplines and learning from major international studies, researchers aim to develop new approaches to predicting, diagnosing and treating lung infections.

Looking ahead

The long-term goal is to identify molecules that can block harmful interactions between microorganisms and demonstrate that they work in laboratory models. These discoveries could then be developed further by drug discovery specialists and eventually tested in clinical studies.

The research offers a different way of thinking about respiratory infection. Instead of focusing only on eliminating individual bacteria, future treatments may also seek to change how microbial communities behave.

By understanding the hidden relationships between microorganisms in the lungs, researchers hope to make antibiotics work more effectively, reduce damaging exacerbations and improve the lives of people living with cystic fibrosis.