Dataset Information

The airway microbiota and exacerbations of COPD.

ABSTRACT: Aim:The aim of this study was to investigate whether the compositionality of the lower airway microbiota predicts later exacerbation risk in persons with COPD in a cohort study. Materials and methods:We collected lower airways microbiota samples by bronchoalveolar lavage and protected specimen brushes, and oral wash samples from 122 participants with COPD. Bacterial DNA was extracted from all samples, before we sequenced the V3-V4 region of the 16S RNA gene. The frequency of moderate and severe COPD exacerbations was surveyed in telephone interviews and in a follow-up visit. Compositional taxonomy and ? and ? diversity were compared between participants with and without later exacerbations. Results:The four most abundant phyla were Firmicutes, Bacteroidetes, Proteobacteria and Fusobacteria in both groups, and the four most abundant genera were Streptococcus, Veillonella, Prevotella and Gemella. The relative abundances of different taxa showed a large variation between samples and individuals, and no statistically significant difference of either compositional taxonomy, or ? or ? diversity could be found between participants with and without COPD exacerbations within follow-up. Conclusion:The findings from the current study indicate that individual differences in the lower airway microbiota in persons with COPD far outweigh group differences between frequent and nonfrequent COPD exacerbators, and that the compositionality of the microbiota is so complex as to present large challenges for use as a biomarker of later exacerbations.

SUBMITTER: Leiten EO

PROVIDER: S-EPMC7456643 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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The airway microbiota and exacerbations of COPD.

Leiten Elise Orvedal EO Nielsen Rune R Wiker Harald Gotten HG Bakke Per Sigvald PS Martinsen Einar Marius Hjellestad EMH Drengenes Christine C Tangedal Solveig S Husebø Gunnar Reksten GR Eagan Tomas Mikal Lind TML

ERJ open research 20200701 3

<h4>Aim</h4>The aim of this study was to investigate whether the compositionality of the lower airway microbiota predicts later exacerbation risk in persons with COPD in a cohort study.<h4>Materials and methods</h4>We collected lower airways microbiota samples by bronchoalveolar lavage and protected specimen brushes, and oral wash samples from 122 participants with COPD. Bacterial DNA was extracted from all samples, before we sequenced the V3-V4 region of the 16S RNA gene. The frequency of moder ...[more]

PMID: 32904583

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Project description:Differential susceptibility to recurrent infection and exacerbation in COPD is not well understood. Here we investigated the potential impact of genetic variation in Fatty Acid Binding Protein 5 (FABP5), a metabolic regulator we previously demonstrated to be downregulated in COPD and further downregulated in patients reporting one or more exacerbation. Through negative binomial analysis of the COPDGene SNP dataset, we identified 5 novel linked single nucleotide polymorphisms (SNPs) across the FABP5 locus that were significantly associated with severe exacerbations in a Non-Hispanic White cohort (rs4338057, rs12549270, rs202275, rs202277, and rs202279). We integrated multiple sources of previously published data to prioritize SNPs most likely to exert regulatory function. Ultimately, rs202275 emerged as the lead candidate due to unique alignment with the loading site of a bidirectional RNA Pol II signature of active enhancer utilization in our recently published patient-derived airway epithelial PRO-seq dataset, suggesting a critical regulatory role for the region harboring this variant. Using Micro-C genome-wide chromosome conformation capture, we found that the region harboring rs202275 makes three-dimensional physical contacts with the FABP5 transcription start site (TSS), suggesting the SNP region could regulate FABP5 transcription through a looping mechanism. To examine SNP function, we analyzed previously deposited gene-array data (GEO Accession #GSE42057) from peripheral blood mononuclear cell (PBMC) samples and found that COPD patients carrying the rs202275 risk allele (T) express significantly lower levels of FABP5 compared to non-carrier patients. Seahorse real-time mitochondrial respiration assays in freshly isolated PBMCs further revealed disrupted oxidative phosphorylation in cells from patients carrying the rs202275 risk allele. As macrophage polarization from pro-inflammatory toward pro-resolving phenotype is dependent on oxidative metabolism, the functional impact of the rs202275 risk allele and associated reduction in FABP5 transcription may contribute to increased or prolonged systemic inflammation, thereby increasing susceptibility to exacerbation in COPD.

Dataset Information

The airway microbiota and exacerbations of COPD.

Publications

The airway microbiota and exacerbations of COPD.

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