Significance of the microbiome in obstructive lung disease

Abstract

The composition of the lung microbiome contributes to both health and disease, including obstructive lung disease. Because it has been estimated that over 70% of the bacterial species on body surfaces cannot be cultured by currently available techniques, traditional culture techniques are no longer the gold standard for microbial investigation. Advanced techniques that identify bacterial sequences, including the 16S ribosomal RNA gene, have provided new insights into the depth and breadth of microbiota present both in the diseased and normal lung. In asthma, the composition of the microbiome of the lung and gut during early childhood development may play a key role in the development of asthma, while specific airway microbiota are associated with chronic asthma in adults. Early bacterial stimulation appears to reduce asthma susceptibility by helping the immune system develop lifelong tolerance to innocuous antigens. By contrast, perturbations in the microbiome from antibiotic use may increase the risk for asthma development. In chronic obstructive pulmonary disease, bacterial colonisation has been associated with a chronic bronchitic phenotype, increased risk of exacerbations, and accelerated loss of lung function. In cystic fibrosis, studies utilising culture-independent methods have identified associations between decreased bacterial community diversity and reduced lung function; colonisation with Pseudomonas aeruginosa has been associated with the presence of certain CFTR mutations. Genomic analysis of the lung microbiome is a young field, but has the potential to define the relationship between lung microbiome composition and disease course. Whether we can manipulate bacterial communities to improve clinical outcomes remains to be seen.

Figure 1

Bacterial classification system using Escherichia coli as an example.

Figure 2

Taxonomic classification of bronchoalveolar lavage samples of healthy people who smoke, patients with chronic obstructive pulmonary disease (COPD) and people who do not smoke with normal spirometry at a phylum level.

Figure 3

Regional heterogeneity is noted in lung microbiota. Multiple samples were harvested from the regions of lung indicated by the arrows on the grey lung schematic in two chronic obstructive pulmonary disease (COPD) explants. Pie diagrams depict the genus level classification of 16S sequences, and the CT images demonstrate the absence of bronchiectasis in the airways adjacent to where samples were obtained. The key for the nine most abundant organisms is provided below the lung schematic. Significant heterogeneity is seen within the lungs from these patients with COPD. ND, not done.