The Human Respiratory Microbiome: Implications and Impact

Alicia B. Mitchell, BMedSci (Hons); Allan R. Glanville, MBBS, MD, FRACP


Semin Respir Crit Care Med. 2018;39(2):199-212. 

In This Article


Multiple studies have investigated the lung microbiota of patients with COPD during stable periods when no evidence of lung infection could be observed. Several sample types including BAL, explanted lung tissue, and expectorated sputum samples have been analyzed. These studies have revealed that the distal airways and alveoli in COPD patients contain a distinct microbiome which may prove relevant to the progression of the disease and the intermittent development of infectious exacerbations.[11] Differences in the bacterial microbiome between individuals with COPD, non-COPD smokers, and nonsmoking controls have been observed. However, Erb-Downward et al did not demonstrate a distinct "COPD" microbiome using sequencing techniques. Instead there was an extensive overlap in the bacterial communities between these three groups but decreased diversity of bacterial species in those with severe COPD.[29,58] When the microbiome was characterized in lung tissue samples using PCR and terminal restriction fragment length polymorphism analysis, the microbiota seen in individuals with severe COPD differed from individuals with CF and mild COPD controls.[29] An increase in microbiome diversity in COPD compared with healthy controls has also been demonstrated using sequencing methods; however, diversity did not seem to correlate with disease severity. Species clustering did occur, however, with the use of inhaled therapy including both bronchodilators and corticosteriods.[59] Spatial heterogeneity of bacterial species within the lung was markedly increased in patients with severe COPD.[58] These shifts in the microbiota in COPD may be explained in part by the decreased surface area of the lung due to alveolar wall breakdown as the disease progresses, which leaves less available terrain for the distribution of the microbiota. This may also be responsible for the increased bacterial burden observed in severe destructive lung diseases.

It has been postulated that changes in the microbiome may underlie exacerbations of COPD. Several studies have compared the composition of the microbiome during stable periods with the composition during an exacerbation to determine if certain bacterial species are associated with worsening symptoms. Sethi et al compared the presence and load of the most common bacterial strains observed during an acute exacerbation and in the stable state of COPD. They found that change in bacterial load is unlikely to be the main mechanism involved in the occurrence of an exacerbation and suggested that host–pathogen interactions were more important.[60] A study by Millares et al showed that colonization with P. aeruginosa in severe COPD did not have significant effects on the biodiversity of the rest of the microbiome. Furthermore, during exacerbations, previous Pseudomonas colonization had little effect on the changes in microbes observed, compared with those who had never been colonized, including an increased abundance of Haemophilus, Streptococcus and Moraxella species.[61] Furthermore, it has been observed that during an exacerbation, movement toward the Proteobacteria phylum, including detection of a range of nontypical COPD pathogens, occurs. Treatment also appeared to be an important factor in microbiome shifts. Antibiotic treatment initially not only decreases Proteobacteria but also induces overall microbiome suppression. Treatment with corticosteroids alone enriched further for members of the Proteobacteria phylum.[62]