Lung microbiome and cytokine profiles in different disease states of COPD: a cohort study

Abstract

AbstractIncreasing evidence indicates that respiratory tract microecological disorders may play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Understanding the composition of the respiratory microbiome in COPD and its relevance to respiratory immunity will help develop microbiome-based diagnostic and therapeutic approaches. One hundred longitudinal sputum samples from 35 subjects with acute exacerbation of COPD (AECOPD) were analysed for respiratory bacterial microbiome using 16S ribosomal RNA amplicon sequencing technology, and the sputum supernatant was analysed for 12 cytokines using a Luminex liquid suspension chip. Unsupervised hierarchical clustering was employed to evaluate the existence of distinct microbial clusters. In AECOPD, the respiratory microbial diversity decreased, and the community composition changed significantly. The abundances ofHaemophilus,Moraxella,Klebsiella, andPseudomonasincreased significantly. Significant positive correlations between the abundance ofPseudomonasand TNF-α, abundance ofKlebsiellaand the percentage of eosinophils were observed. Furthermore, COPD can be divided into four clusters based on the respiratory microbiome. AECOPD-related cluster was characterized by the enrichment ofPseudomonasandHaemophilusand a high level of TNF-α.LactobacillusandVeillonellaare enriched in therapy-related phenotypes and may play potential probiotic roles. There are two inflammatory endotypes in the stable state:Gemellais associated with the Th2 inflammatory endotypes, whereasPrevotellais associated with the Th17 inflammatory endotypes. Nevertheless, no differences in clinical manifestations were found between these two endotypes. The sputum microbiome is associated with the disease status of COPD, allowing us to distinguish different inflammatory endotypes. Targeted anti-inflammatory and anti-infective therapies may improve the long-term prognosis of COPD.