At the Festival of Genomics & Biodata 2025, Dr Michael Cox from the Institute of Microbiology and Infection at the University of Birmingham spoke about how the respiratory microbiome plays a crucial role in lung health and disease. The lungs are not sterile; rather, they harbour a dynamic microbial community. However, studying this microbiome presents challenges due to the difficulty of obtaining samples that do not become contaminated with the microbiome of the upper respiratory tract. Despite this, researchers have identified persistent and distinct microbial signals within the lungs, which are influenced by both inhalation and clearance processes. When these processes are disrupted, as seen in conditions such as cystic fibrosis, the microbiome profile changes dramatically.
Healthy vs. diseased microbiomes
In healthy individuals, the predominant bacterial species in the lungs are strict anaerobes, and the microbiome composition remains relatively consistent across the healthy population. However, in disease states, microbial diversity increases, and certain diseases exhibit distinct microbiome signatures. For instance, the microbiomes of patients with asthma and chronic obstructive pulmonary disease (COPD) can be differentiated, which may aid in disease classification. Notably, the lung microbiome is distinct from that of the nasal passages, with the latter showing greater microbial diversity.
Insights from the Celtic Fire Study
A key study examining severe asthma, the Celtic Fire Study, collected bronchoscopic samples from both healthy individuals and patients with asthma. The study also incorporated blood samples, throat swabs, lung brushes, biopsies, and questionnaires. One of the significant findings was the ability to use spatial transcriptomics to localise bacterial communities within different tissue regions. This approach revealed bacteria in the stroma of asthmatic patients, a phenomenon not observed in healthy individuals. Using RNA scope 16S probes, researchers established an association between 16S sequencing data and transcriptional network clusters, which were predominantly linked to immune system responses.
The role of macrophages in shaping the microbiome
Macrophages, key immune cells, play a pivotal role in regulating the lung microbiome. In diseases such as COPD, both genetic and environmental factors contribute to changes in microbiome composition. Macrophages are responsible for engulfing and destroying bacteria, but in diseased states, they exhibit altered behaviour—attracting other inflammatory cells while becoming inefficient in bacterial clearance. This dysfunction results in significant differences in bacterial survival between healthy and diseased lungs.
Microbiome-macrophage interactions
The interactions between macrophages and bacteria are complex, with a vast number of possible bacterial combinations within macrophages. For example, Haemophilus influenzae is never taken up by macrophages in isolation, and some bacterial species are phagocytosed more rapidly than others. Studies have shown that macrophages from healthy individuals, particularly young individuals, are more efficient at engulfing bacteria compared to those from progressively aged or diseased samples.
The respiratory microbiome is a dynamic and integral component of lung health. The interplay between microbial communities and immune cells such as macrophages highlights the complexity of respiratory diseases. Advances in spatial transcriptomics and single-cell imaging are improving our understanding of how microbiomes influence immune responses, offering potential avenues for novel therapeutic interventions in respiratory diseases.