Based on respiratory tract microbiome profiles of a cohort of healthy individuals and COPD patients from different geographical regions, representative of diverse ethnicities and environmental exposures, we found that both COPD disease status and geography had an impact on the respiratory tract microbiome. The alterations in respiratory tract microbiome are potentially related to the pathological state or pathogenesis of COPD.
The predominant microbial families in sputum and oropharyngeal swabs are largely the same, indicating a continuum of microbiome composition along the respiratory tract. Previous studies showed that in healthy individuals Bacteroidetes and Firmicutes are two predominant phyla, whereas at the genus level, Prevotella, Veillonella, and Streptococcus are highly abundant in sputum microbiome[16–18]. The sputum microbiome is more diverse than the oropharyngeal swab, consistent with the fact that sputum microbiome is a mixture of oral and upper/lower respiratory tract microbiomes.
Reduced diversity of sputum microbiome under COPD stable state compared with healthy state has been reported in previous studies. Moreover, the diversity of sputum microbiome has been found to be further decreased at exacerbations. We found a consistent decreasing pattern in sputum microbiome; however, the oropharyngeal swab microbiome showed an increase in COPD compared with healthy control, which needs to be confirmed in further studies with balanced sample distribution between groups.
Pair-wise comparison of patients and healthy controls who shared the same household help reduce confounding factors, such as diet and genetic factors, and may reveal true microbiome alterations associated with diseases. Identified enriched or depleted taxa within COPD respiratory microbiome may underlie COPD pathogenesis or be a reflection of the pathological status. Some of the taxa found to be increased under COPD stable state have been reported to be associated with COPD before, such as Actinomyces, Veillonella, and Rothia. In addition, Actinobacillus was also markedly enriched under COPD stable state, which was discovered as an aggressive pathogen related to periodontitis. Previous studies have shown that the COPD respiratory tract microbiome became more abundant in Proteobacteria bacteria such as Pseudomonas spp. and Haemophilus spp.[20–22]. In our study, many bacterial clades under Proteobacteria were observed to be increased in abundance in COPD patients during exacerbations compared with healthy individuals, including Enterobacteriaceae spp., Gammaproteobacteria spp., Comamonadaceae spp., Alphaproteobacteria spp., Rhodobacteraceae spp., Raoultella, and Haemophilus. Raoultella is considered as opportunistic pathogens that may result in pneumonia in individuals with abnormal immunity. Haemophilus contains the well-known opportunistic pathogen Haemophilus influenzae, and respiratory infection by this bacterium causes airway inflammation and is linked to respiratory diseases including COPD. Though still a conjecture, these clades may contribute to episodic exacerbations in COPD patients.
This study was initially based on the results of the population study, compared with the results generated from the core-family study, and the follow-up microbe’s biological function verification study can be focused on the identical microbes. However, there are still many limitations. First, sample sizes across different groups were imbalanced, due to difficulty in collecting respiratory microbiome samples. Second, the sample sizes for intra-household pairwise comparisons of healthy control vs COPD and healthy control vs AECOPD were quite limited, which still help eliminate confounding factors related to microbiome compositions. Third, few individuals had both sputum and oropharyngeal swab samples available, not allowing for comparing upper and lower microbiome within individuals. Fourth, due to small sample size at one geographical location, whether patients of different ethnics/locations in healthy or COPD respiratory tract microbiome between cannot be investigated.