Asthma and lower airway diseaseFeatures of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment
Graphical abstract
Section snippets
Study population and sample collection
This study was conducted at 9 sites in the National Heart, Lung, and Blood Institute AsthmaNet network by using a standardized bronchoscopy protocol for sample collection. Of 186 adults screened, 84 subjects were enrolled (see Fig E1, A and B, in this article's Online Repository at www.jacionline.org): 42 atopic asthmatic subjects (AAs), 21 atopic nonasthmatic subjects (ANAs), and 21 nonatopic healthy control subjects (HCs). Atopy was defined based on serologic evidence (>0.35 kU/L) of
Study group characteristics
AAs had mild well-controlled disease and significantly higher serum total IgE levels and blood and sputum eosinophil counts (Table I and see Fig E2, A-C, in this article's Online Repository at www.jacionline.org) than HCs. Compared with the ANAs, asthmatic subjects had significantly higher serum IgE levels; were sensitized to more of the aeroallergens tested (Table I); were more likely to be sensitive to cat, dog, and mouse (see Table E1); and were more likely to report a history of allergic
Discussion
Our findings show compositional and predicted functional differences in the bronchial bacterial microbiomes of AAs, ANAs, and HCs. An important implication of these findings is that control for allergic sensitization is necessary in studies aimed at understanding differences in the respiratory microbiome associated with asthma. Despite overlap in bacterial genera significantly associated with both atopic groups, our study identified specific bacterial taxa whose relative enrichment or depletion
References (52)
- et al.
Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways
J Allergy Clin Immunol
(2016) - et al.
The airway microbiome in patients with severe asthma: associations with disease features and severity
J Allergy Clin Immunol
(2015) - et al.
Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis
J Allergy Clin Immunol
(2014) Conservation evaluation and phylogenetic diversity
Biol Conserv
(1992)- et al.
The interpersonal and intrapersonal diversity of human-associated microbiota in key body sites
J Allergy Clin Immunol
(2012) - et al.
Eosinophils in mucosal immune responses
Mucosal Immunol
(2015) - et al.
The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development
Cell Host Microbe
(2015) - et al.
Azithromycin inhibits nontypeable Haemophilus influenzae-induced MUC5AC expression and secretion via inhibition of activator protein-1 in human airway epithelial cells
Eur J Pharmacol
(2010) - et al.
Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function
Cell Host Microbe
(2015) - et al.
Effects of low-dose doxycycline on cytokine secretion in human monocytes stimulated with Aggregatibacter actinomycetemcomitans
Cytokine
(2011)
The effects of airway microbiome on corticosteroid responsiveness in asthma
Am J Respir Crit Care Med
Disordered microbial communities in asthmatic airways
PLoS One
Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma
J Allergy Clin Immunol
Asthma-associated differences in microbial composition of induced sputum
J Allergy Clin Immunol
Associations of asthma with serum IgE levels and skin-test reactivity to allergens
N Engl J Med
How much asthma is really attributable to atopy?
Thorax
Allergic rhinitis, chronic rhinosinusitis and asthma: unravelling a complex relationship
Curr Opin Otolaryngol Head Neck Surg
Development and validation of a questionnaire to measure asthma control
Eur Respir J
Oral and airway microbiota in HIV-infected pneumonia patients
J Clin Microbiol
Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms
ISME J
Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample
Proc Natl Acad Sci U S A
Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB
Appl Environ Microbiol
FastTree: computing large minimum evolution trees with profiles instead of a distance matrix
Mol Biol Evol
Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids
Proc Natl Acad Sci U S A
T-helper type 2-driven inflammation defines major subphenotypes of asthma
Am J Respir Crit Care Med
A qPCR-based metric of Th2 airway inflammation in asthma
Clin Transl Allergy
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Disclosure of potential conflict of interest: S. V. Lynch has received grants from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Disease (NIAID; AI113916, AI089473-01, and AI097172), Janssen, the Broad Foundation, the Sloan Foundation, Pfizer, the NIH/National Institute of Child Health and Human Development (HD082147-01), the NIH/National Heart, Lung, and Blood Institute (NHLBI; HL098107 and HL098964), and the NIH/National Institute of Diabetes and Digestive and Kidney Diseases (DK104664); has a patent Stan449-PRV REDUCTIVE PRODRUG CANCER CHEMOTHERA issued, a patent Combination antibiotic and antibody therapy for the treatment of Pseudomonas aeruginosa infection with royalties paid, a patent provisional filing for use of Lactobacillus sakei and other lactic acid bacteria as a therapeutic strategy for chronic rhinosinusitis issued, a patent provisional filing for claims associated with use of PhyloChip as a diagnostic and prognostic clinical tool issued, and a patent Bacterial Therapeutic Consortium for induction of Immune Tolerance pending. S. Nariya has received a grant from the NHLBI and the National Institute of Allergy and Infectious Disease (NIAID). N. R. Bhakta has received a grant from the NIH/NHLBI and has received personal fees from Roche/Genentech. M. Castro has received personal fees from Boston Scientific, Holaira, Genentech, Teva, GlaxoSmithKline, Boehringer Ingelheim, Elsevier, and Neostem; has received grants from Amgen, Teva, Novartis, GlaxoSmithKline, Sanofi-Aventis, Vectura, Boehringer Ingelheim, MedImmune, Invion, and Pfizer; and owns stock in Sparo. A.-.M. Dyer has received a grant from the NHLBI. E. Israel has received personal fees from AstraZeneca, Novartis, Philips Respironics, Regeneron Pharmaceuticals, Campbell, Campbell, Edwards & Conroy, Crammer, Bishop & O'Brien, Fox Rothschild, Ryan Deluca LLP, TEVA Specialty Pharmaceuticals, UpToDate, Cowen & Co, Bird Rock Bio, Nuvelution Pharmaceuticals, and Vitaeris; has received a grant from Genentech and Sanofi; has received nonfinancial support from Boehringer Ingelheim, GlaxoSmithKline, Merck, Sunovion, and TEVA; and has received other compensation from Novartis, Research in Real Life, and TEVA Specialty Pharmaceuticals. R. J. Martin has received a grant from MedImmune; has received personal fees from Teva, AstraZeneca, and Genentech; and has received travel support from the Respiratory Effectiveness Group. D. T. Mauger has received a grant from the NHLBI and has received nonfinancial support from GlaxoSmithKline, Merck, Boehringer Ingelheim, Teva, and Sunovion. S. R. Rosenberg has received grants from AstraZeneca and Boehringer Ingelheim. T. Sharp-King has received a grant from the NHLBI and has received personal fees from Pearl Therapeutics and Insmed. S. R. White has received grants from the NIAID (U19-AI-095230) and AstraZeneca and has received personal fees from Marathon Pharmaceuticals. P. G. Woodruff has received personal fees from Genentech, Johnson & Johnson, Roche, and Neostem and has a patent pending related to asthma biomarkers with Genentech. P. C. Avila has received grants from the NIH/NHLBI, Genentech, AstraZeneca, and Novartis. L. C. Denlinger has received a grant from the NIH/NHLBI and has received personal fees from Novartis and GlaxoSmithKline. S. C. Lazarus has received a grant from the NIH/NHLBI and has received personal fees from Respiratory Disease Young Investigators' Research Forum. N. Lugogo has received a grant from the NIH. W. C. Moore has received a grant from the NHLBI. S. P. Peters has received a grant from the NIH/NHLBI. C. A. Sorkness has received grants from the NHLBI and the NIAID. M. E. Wechsler has received personal fees from Sepracor/Sunovion, Asthmatx/BSCI, Merck, Regeneron, MedImmune, Ambitbio, Vectura, Sanofi, Teva, Mylan, AstraZeneca, Genentech, Meda, Theravance, Novartis, Boehringer Ingelheim, GlaxoSmithKline, Tunitas, and Gliacure. S. E. Wenzel has received grants from Sanofi, Genentech, AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim and has received personal fees from AstraZeneca, Aerocrine, GlaxoSmithKline, Actelion, and Boehringer Ingelheim. H. A. Boushey has received grants from the NIH/NHBI and the NIH/NIAID and has received personal fees from the McGraw-Hill Companies. Y. J. Huang has received grants from the NHLBI (K23HL105572) and the Michigan Institute of Health and Clinical Research, has received travel and lodging compensation from the NIH, and has received payment for lectures from the American Academy of Allergy, Asthma & Immunology; the Massachusetts Institute of Technology; the European Respiratory Society; the Microbiome R&D Business Forum; and the European Academy of Allergy, Asthma, and Clinical Immunology. The rest of the authors declare that they have no relevant conflicts of interest.