Understanding the role of the microbiome in chronic obstructive pulmonary disease: principles, challenges, and future directions

Abstract

In the past several years, advances in sequencing platforms and bioinformatics have transformed our understanding of the relationship between microbial ecology and human health. Both the normal and diseased lung are host to hundreds of bacterial genera, blurring the lines between "colonization" and "infection". However, whereas in health the respiratory microbiome is determined primarily by the dynamic balance of immigration and elimination, in chronic disease conditions become much more favorable for the reproduction of resident bacteria. Recent studies demonstrate that the microbiota of the chronic obstructive pulmonary disease (COPD) lung differ from the healthy lung although significant intrasubject and intersubject heterogeneity are still present with variation impacted by factors such as disease stage and inhaled medications. Changes in the relative abundance of specific bacterial taxa during COPD exacerbations have also been noted although further longitudinal analyses are needed to ascertain the malleability and resilience of this ecological system and its role in the occurrence and frequency of exacerbations. Whether patients with a "frequent exacerbator" phenotype possess specific or greater alterations in their airway microbiome that predispose them to recurrent exacerbations as compared with nonfrequent exacerbators needs to be determined. Although recent data suggest that the presence of bacteria has the potential to influence the host immune response, a key challenge in the next few years will be to continue to move beyond descriptive studies to define the clinical relevance of differences in lung microbiota associated with COPD.

Figure 1

Correlations between the relative abundance of H. influenzae (a member of the Pasteurellaceae/Gammaproteobacteria) and that of all other identified taxa. The analysis was performed using data from all 60 samples in this study. Significant positive and negative correlations are shown (Pearson R≥0.5, Benjamini-Hochberg-adjusted P<0.05). Positive correlations (red) occur predominantly with members of Pasteurellaceae or closely related bacterial families and classes of Proteobacteria. Negative correlations (blue) occur with bacterial families and classes that phylogenetically are more distant to H. influenzae/Pasteurellaceae. Tree branches are color coded by bacterial class in the key on the right.