Airway microbiome alterations linked to atopy, mild asthma, and steroid-response

Published online: November 9, 2016

Previous studies have shown that characteristics of the bronchial airway microbiome are associated with distinct features of asthma in suboptimally controlled, more severe disease (Huang et al. The Journal of Allergy and Clinical Immunology (JACI) 2011 and 2015). This has suggested important relationships between airway microbial community composition and asthma phenotype, but it has remained unclear if such findings are attributable to asthma itself, to aeroallergen sensitization commonly present in asthmatic patients, or to ongoing inhaled corticosteroid (ICS) treatment.

To address this, the National Heart, Lung and Blood Institute’s AsthmaNet performed a study that prospectively investigated the airway microbiome in adults with mild atopic asthma not on chronic ICS therapy, atopic subjects without asthma, and healthy non-atopic subjects. After baseline assessments including bronchoscopy, the asthmatic group was randomized to six weeks of treatment with fluticasone propionate or a placebo inhaler, after which bronchoscopy was repeated. Protected bronchial brushings were analyzed for bacterial microbiota composition and epithelial markers of type 2 inflammation. Further analyses were performed to determine if compositional and functional characteristics of identified bacterial communities were linked to features of mild asthma, including the level of type 2 inflammation present and response to fluticasone.

As hypothesized, significant between-group differences in the bronchial bacterial microbiome were seen. Compared to both control groups, asthmatic subjects were enriched in members of the Haemophilus, Neisseria, Fusobacterium, Porphyromonas and Sphingomonodaceae, and depleted in members of the Mogibacteriaceae and Lactobacillales. Predictive metagenomic analysis indicated asthma-related differences in bacterial functions involved in amino acid and short-chain fatty acid metabolism. Moreover, type 2-“high” asthmatic subjects demonstrated significantly lower bronchial bacterial burden than did type 2-“low” subjects. After fluticasone treatment, distinct changes in specific bacterial microbiota were seen, and ICS-responsiveness was linked to differences in baseline compositional and functional features of the bronchial bacterial microbiome. Finally, aeroallergen-sensitized subjects without asthma also displayed alterations in the bronchial bacterial microbiome that were distinct from either the asthmatic or non-atopic healthy group.   

Several novel observations in this multi-center study add importantly to the literature on links between the airway microbiome and asthma phenotype in adult patients. First, it provides evidence that in the absence of corticosteroid use the bronchial microbiome is altered in mild asthma. Second, type 2-“low” asthmatic subjects in this cohort demonstrated greater bronchial bacterial burden and bacterial dysbiosis, in contrast to type 2-“high” subjects, consistent with prior observations in severe asthma of negative or absent relationships between markers of type 2 inflammation and the bronchial bacterial microbiome (Huang et al. JACI 2015). Finally, the study also highlights that controlling for atopy is an important consideration for studies of the airway microbiome in asthma and that the effects of and response to ICS treatment may have important connections to the airway microbiota present.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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