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Respir Res. 2019 Jun 6;20(1):113. doi: 10.1186/s12931-019-1085-z.

Airway host-microbiome interactions in chronic obstructive pulmonary disease.

Author information

1
Computational Biology, Human Genetics, Research and Development (R&D), GlaxoSmithKline (GSK), 1250 S. Collegeville Road, Collegeville, PA, 19426-0989, USA.
2
Present Address: School of Life Sciences, South China Normal University, Guangzhou, 510631, People's Republic of China.
3
Refractory Respiratory Inflammation Discovery Performance Unit, Respiratory Therapy Area, R&D, GSK, Stevenage, SG1 2NY, UK.
4
University of Manchester and University Hospital of South Manchester, Manchester, M23 9QZ, UK.
5
Functional Genomics, Medicinal Science and Technology, R&D, GSK, Collegeville, PA, 19426, USA.
6
Computational Biology, Human Genetics, Research and Development (R&D), GlaxoSmithKline (GSK), 1250 S. Collegeville Road, Collegeville, PA, 19426-0989, USA. James.R.Brown@gsk.com.

Abstract

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.

KEYWORDS:

COPD; Chronic obstructive pulmonary disease; Clinical study; Exacerbations; Healthy; Microbiome; Next-generation sequencing technologies; Proteome; Smokers; Transcriptome

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