Dataset Information

Airway host-microbiome interactions in chronic obstructive pulmonary disease.

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.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6555748 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Airway host-microbiome interactions in chronic obstructive pulmonary disease.

Wang Zhang Z Maschera Barbara B Lea Simon S Kolsum Umme U Michalovich David D Van Horn Stephanie S Traini Christopher C Brown James R JR Hessel Edith M EM Singh Dave D

Respiratory research 20190606 1

<h4>Background</h4>Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).<h4>Methods</h4>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.<h4>Results</h4>Dysbiosis of sputum microbiome was observed with significantly increased relative abu ...[more]

PMID: 31170986

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Project description:<p>The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe-host interactions in COPD by an in-depth profiling of sputum metagenome, metabolome, host transcriptome and proteome from 99 COPD patients and 36 healthy individuals. Multi-omic data were integrated using a sequential mediation analysis, to assess in silico associations of the microbiome with neutrophilic or eosinophilic inflammation, two primary COPD inflammatory endotypes, mediated through microbial metabolic interaction with host gene expression. Mechanistic links of microbiome-metabolite-host interaction were identified leveraging microbial genetic information and established metabolite-human gene pairs. The strongest link for neutrophil-predominant COPD was altered tryptophan metabolism driven by airway lactobacilli resulting in reduced indole-3-acetic acid (IAA), which was in turn linked to perturbed host IL-22 signaling and epithelial cell apoptosis pathways. In vivo and in vitro studies showed that airway microbiome-derived IAA mitigates neutrophilic inflammation, apoptosis, emphysema, and lung function decline, via IL-22-mediated macrophage-epithelial cell crosstalk. Intranasal inoculation of two airway lactobacilli restored IAA and recapitulated its protective effects in mice. These findings provide the rationale for therapeutically targeting microbe-host interaction in COPD.</p><p><br></p><p><strong>Linked studies:</strong></p><p><strong>UPLC-MS/MS assays</strong> of original cohort human samples are reported in this study.</p><p><strong>UPLC-MS/MS assays</strong> of more recent cohort human samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS5423' rel='noopener noreferrer' target='_blank'><strong>MTBLS5423</strong></a>.</p><p><strong>UPLC-MS/MS assays</strong> of more recent murine samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6894' rel='noopener noreferrer' target='_blank'><strong>MTBLS6894</strong></a>.</p>

Project description:Little is known about the underlying airway microbiome diversity in chronic obstructive pulmonary disease (COPD) at in-depth taxonomic levels. Here we present the first insights on the COPD airway microbiome at species and strain-levels. The full-length 16S rRNA gene was characterized from sputum in 98 COPD patients and 27 age-matched healthy controls, using the Pacific Biosciences sequencing platform. Individual species within the same genus exhibited reciprocal relationships with COPD and disease severity. Species dominant in health can be taken over by another species within the same genus but with potentially increasing pathogenicity in severe COPD patients. Ralstonia mannitolilytica, an opportunistic pathogen, was significantly increased in frequent exacerbators (fold-change = 4.94, FDR P = 0.005). There were distinct patterns of interaction between bacterial species and host inflammatory mediators according to neutrophilic or eosinophilic inflammations, two major airway inflammatory phenotypes in COPD. Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Neisseria meningitidis were associated with enhanced Th1, Th17 and pro-inflammatory mediators, while a group of seven species including Tropheryma whipplei were specifically associated with Th2 mediators related to eosinophilia. We developed an automated pipeline to assign strain-level taxonomy leveraging bacterial intra-genomic 16S allele frequency. Using this pipeline we further resolved three non-typeable H. influenzae strains PittEE, PittGG and 86-028NP with reasonable precision and uncovered strain-level variation related to airway inflammation. In particular, 86-028NP and PittGG strains exhibited inverse associations with Th2 chemokines CCL17 and CCL13, suggesting their abundances may inversely predict eosinophilic inflammation. A systematic comparison of 16S hypervariable regions indicated V1V3 instead of the commonly used V4 region was the best surrogate for airway microbiome. The full-length 16S data augmented the power of functional inference, which slightly better recapitulated the actual metagenomes. This led to the unique identification of butyrate-producing and nitrate reduction pathways as depleted in COPD. Our analysis uncovered finer-scale airway microbial diversity that was previously underappreciated, thus enabled a refined view of the airway microbiome in COPD.

Dataset Information

Airway host-microbiome interactions in chronic obstructive pulmonary disease.

Publications

Airway host-microbiome interactions in chronic obstructive pulmonary disease.

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