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. 2016 May;137(5):1398-1405.e3.
doi: 10.1016/j.jaci.2015.10.017. Epub 2015 Nov 25.

Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways

Darcy R Denner  1 , Naseer Sangwan  2 , Julia B Becker  1 , D Kyle Hogarth  1 , Justin Oldham  1 , Jamee Castillo  1 , Anne I Sperling  1 , Julian Solway  1 , Edward T Naureckas  1 , Jack A Gilbert  3 , Steven R White  4
Affiliations

Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways

Darcy R Denner et al. J Allergy Clin Immunol. 2016 May.

Abstract

Background: The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear.

Objectives: We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia.

Methods: DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics.

Results: Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils.

Conclusion: The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use.

Keywords: 16S ribosomal RNA; Asthma; FEV(1); bacteria; corticosteroids; microbiome.

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Figures

Figure 1
Figure 1
Relative abundance (%) of bacteria at the (A) phylum and (B) genera level identified in each sampling group.
Figure 2
Figure 2
Analysis of microbial communities by sampling location. A. Alpha diversity of all samples according to location.. B. Ordination plot of principle component analysis of beta-diversity of EB, BAL, and negative control samples. C. and D. Significantly, differentially abundant genera in EB-Asthma versus BAL-Asthma (C) and EB-Control versus BAL-Control (D) samples.
Figure 3
Figure 3
Differentially abundant genera across asthmatic and control subjects. A. Significantly differential genera between EB-Asthmatics and EB-control samples. B. Significantly differential genera between BAL-Asthmatic and BAL-Control samples.
Figure 4
Figure 4. Generalized linear model fitting analysis across significantly important taxa (Genera as predicted by MetagenomeSeq) across Asthma samples
For each genus GLM model was constructed, validated and analyzed using analysis of variance (ANOVA). * P < 0.05.
Figure 5
Figure 5
Mixed model regression demonstrating a relationship between Shannon (top panel) and Inverse Simpson (bottom panel) measurements of diversity and FEV1, corticosteroid use, white ancestry, and BAL eosinophils for EB-Asthmatic samples only.
See this image and copyright information in PMC

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