Juliana Durack1, Susan V Lynch1, Snehal Nariya2, Nirav R Bhakta3, Avraham Beigelman4, Mario Castro5, Anne-Marie Dyer6, Elliot Israel7, Monica Kraft8, Richard J Martin9, David T Mauger6, Sharon R Rosenberg10, Tonya Sharp-King6, Steven R White11, Prescott G Woodruff3, Pedro C Avila10, Loren C Denlinger12, Fernando Holguin13, Stephen C Lazarus3, Njira Lugogo14, Wendy C Moore15, Stephen P Peters15, Loretta Que14, Lewis J Smith10, Christine A Sorkness12, Michael E Wechsler9, Sally E Wenzel13, Homer A Boushey16, Yvonne J Huang2. 1. Department of Medicine, Division of Gastroenterology, University of California, San Francisco, Calif. 2. Division of Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, Mich. 3. Department of Medicine, University of California, San Francisco, Calif. 4. Division of Pediatrics, Washington University School of Medicine, St Louis, Mo. 5. Division of Pediatrics, Washington University School of Medicine, St Louis, Mo; Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, Mo. 6. Department of Public Health Sciences, Penn State University, Hershey, Pa. 7. Department of Medicine, Brigham & Women's Hospital, Boston, Mass. 8. Health Sciences, University of Arizona, Tucson, Ariz. 9. Department of Medicine, National Jewish Hospital, Denver, Colo. 10. Department of Medicine, Northwestern University, Chicago, Ill. 11. Department of Medicine, University of Chicago, Chicago, Ill. 12. Department of Medicine, University of Wisconsin-Madison, Madison, Wis. 13. University of Pittsburgh Asthma Institute at UPMC/UPSOM, Pittsburgh, Pa. 14. Duke Asthma, Allergy & Airway Center, Duke University School of Medicine, Durham, NC. 15. Wake Forest School of Medicine, Winston-Salem, NC. 16. Department of Medicine, University of California, San Francisco, Calif. Electronic address: homer.boushey@ucsf.edu.
Abstract
BACKGROUND: Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment. OBJECTIVES: We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma. METHODS: Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment. RESULTS: The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. CONCLUSION: Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.
RCT Entities:
BACKGROUND: Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment. OBJECTIVES: We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma. METHODS: Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment. RESULTS: The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. CONCLUSION: Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.
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