Airway host-microbiome interactions in chronic obstructive pulmonary disease

• Published in: Respiratory research Vol. 20; no. 1; pp. 113 - 14
• Main Authors: Wang, Zhang, Maschera, Barbara, Lea, Simon, Kolsum, Umme, Michalovich, David, Van Horn, Stephanie, Traini, Christopher, Brown, James R., Hessel, Edith M., Singh, Dave
• Format: Journal Article
• Language: English
• Published: London BioMed Central 06.06.2019; BioMed Central Ltd; BMC
• Subjects: Aged; Antibiotics; Bacterial infections; Care and treatment; Cell adhesion & migration; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Clinical study; COPD; Cytokines; Development and progression; Dysbacteriosis; Exacerbations; Female; Gene expression; Gene Expression Profiling - methods; Haemophilus; Haemophilus influenzae - genetics; Health aspects; Health care; Host Microbial Interactions - physiology; Host-bacteria relationships; Humans; Immune response; Immune system; Infectious diseases; Inflammation; Interferon; Leukocytes (neutrophilic); Longitudinal Studies; Lung - microbiology; Lung - physiology; Lung diseases; Male; Medicine; Medicine & Public Health; Microbiome; Microbiomes; Microbiota (Symbiotic organisms); Microbiota - physiology; Middle Aged; Moraxella; Moraxella - genetics; Neutrophilia; Obstructive lung disease; Pneumology/Respiratory System; Proteomes; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - microbiology; Relative abundance; Respiratory tract; rRNA 16S; Signal transduction; Signaling; Smoking; Sputum; Sputum - microbiology; Sputum - physiology; Streptococcus infections; Transcriptome; United States; Smokers; Transcriptome; Exacerbations; Proteome; Chronic obstructive pulmonary disease; Next-generation sequencing technologies; Healthy; COPD; Microbiome; Clinical study
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-019-1085-z

Background Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD). Methods We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients. Results Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers. Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus , host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD. While neutrophilia was positively correlated with Haemophilus , interferon signaling was more strongly linked to Moraxella. Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella -associated host responses were primarily related to exacerbations. Conclusions Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations. These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.