Airway host-microbiome interactions in chronic obstructive pulmonary disease

Zhang Wang,Dave Singh,James R Brown,Umme Kolsum,Simon Lea,David Michalovich,Stephanie Van Horn,Barbara Maschera,Christopher Traini,Edith M Hessel

doi:10.1186/s12931-019-1085-z

Abstract

BackgroundLittle is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).MethodsWe 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.ResultsDysbiosis 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.ConclusionsOur 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.

Highlights

Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD)
The human microbiome in the respiratory tract differs between healthy subjects and COPD patients [5,6,7], shifts in composition during COPD exacerbations [8,9,10,11,12] and varies among exacerbation subtypes [9], all suggesting a close association between the lung microbiome and COPD pathophysiology with potential involvement of
Sputum microbiome between healthy and COPD and during exacerbations Sputum microbiome was characterized for 101 sputum samples (Fig. 1a) from COPD patients (Fig. 1b) and healthy controls (Fig. 1c)

Summary

Introduction

Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD). A previous study on COPD patients showed that the lung microbiome was significantly associated with sputum pro-inflammatory markers especially interleukin (IL8/CXCL-8, 9). Few studies have simultaneously characterized both lung microbiome and human multi-omics profiles in COPD, and in other respiratory diseases in general. Sze et al measured the lung microbiome and host transcriptome in COPD and found Firmicutes and Proteobacteria were associated with different host gene expression profiles [14]. Molyneaux et al profiled both lung microbiome and peripheral whole-blood transcriptome for idiopathic pulmonary fibrosis patients and identified two gene modules involved in host defense that are strongly associated with the microbiome profile [15] a comprehensive understanding of the collective host response at both transcriptional and protein expression levels to the lung microbiome community is lacking. A systems biology approach integrating lung microbiome and host multi-omics datasets is necessary to better understand host-microbiome interactions in COPD

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Discussion

Conclusion