Juliana Durack1, Laura S Christian2, Snehal Nariya3, Jeanmarie Gonzalez2, Nirav R Bhakta3, K Mark Ansel2, Avraham Beigelman4, Mario Castro5, Anne-Marie Dyer6, Elliot Israel7, Monica Kraft8, Richard J Martin9, David T Mauger6, Stephen P Peters10, Sharon R Rosenberg11, Christine A Sorkness12, Michael E Wechsler9, Sally E Wenzel13, Steven R White14, Susan V Lynch1, Homer A Boushey3, Yvonne J Huang15. 1. Department of Medicine, Division of Gastroenterology, University of California, San Francisco, Calif. 2. Department of Microbiology & Immunology and Sandler Asthma Basic Research Center, San Francisco, Calif. 3. Department of Medicine, Division of Pulmonary/Critical Care Medicine, University of California, San Francisco, Calif. 4. Division of Pediatric Allergy, Immunology, and Pulmonary Medicine, Washington University School of Medicine, St Louis, Mo; Kipper Institute of Allergy and Immunology, Schneider Children's Medical Center of Israel, Tel Aviv University, Tel Aviv, Israel. 5. 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. University of Arizona, Health Sciences, Tucson, Ariz. 9. Department of Medicine, National Jewish Hospital, Denver, Colo. 10. Wake Forest School of Medicine, Winston-Salem, NC. 11. Department of Medicine, Northwestern University, Chicago, Ill. 12. Department of Medicine, University of Wisconsin-Madison, Madison, Wis. 13. University of Pittsburgh Asthma Institute at UPMC/UPSOM, Pittsburgh, Pa. 14. Department of Medicine, University of Chicago, Chicago, Ill. 15. Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, University of Michigan, Ann Arbor, Mich. Electronic address: yvjhuang@umich.edu.
Abstract
BACKGROUND: Whether microbiome characteristics of induced sputum or oral samples demonstrate unique relationships to features of atopy or mild asthma in adults is unknown. OBJECTIVE: We sought to determine sputum and oral microbiota relationships to clinical or immunologic features in mild atopic asthma and the impact on the microbiota of inhaled corticosteroid (ICS) treatment administered to ICS-naive subjects with asthma. METHODS: Bacterial microbiota profiles were analyzed in induced sputum and oral wash samples from 32 subjects with mild atopic asthma before and after inhaled fluticasone treatment, 18 atopic subjects without asthma, and 16 nonatopic healthy subjects in a multicenter study (NCT01537133). Associations with clinical and immunologic features were examined, including markers of atopy, type 2 inflammation, immune cell populations, and cytokines. RESULTS: Sputum bacterial burden inversely associated with bronchial expression of type 2 (T2)-related genes. Differences in specific sputum microbiota also associated with T2-low asthma phenotype, a subgroup of whom displayed elevations in lung inflammatory mediators and reduced sputum bacterial diversity. Differences in specific oral microbiota were more reflective of atopic status. After ICS treatment of patients with asthma, the compositional structure of sputum microbiota showed greater deviation from baseline in ICS nonresponders than in ICS responders. CONCLUSIONS: Novel associations of sputum and oral microbiota to immunologic features were observed in this cohort of subjects with or without ICS-naive mild asthma. These findings confirm and extend our previous report of reduced bronchial bacterial burden and compositional complexity in subjects with T2-high asthma, with additional identification of a T2-low subgroup with a distinct microbiota-immunologic relationship.
BACKGROUND: Whether microbiome characteristics of induced sputum or oral samples demonstrate unique relationships to features of atopy or mild asthma in adults is unknown. OBJECTIVE: We sought to determine sputum and oral microbiota relationships to clinical or immunologic features in mild atopic asthma and the impact on the microbiota of inhaled corticosteroid (ICS) treatment administered to ICS-naive subjects with asthma. METHODS: Bacterial microbiota profiles were analyzed in induced sputum and oral wash samples from 32 subjects with mild atopic asthma before and after inhaled fluticasone treatment, 18 atopic subjects without asthma, and 16 nonatopic healthy subjects in a multicenter study (NCT01537133). Associations with clinical and immunologic features were examined, including markers of atopy, type 2 inflammation, immune cell populations, and cytokines. RESULTS: Sputum bacterial burden inversely associated with bronchial expression of type 2 (T2)-related genes. Differences in specific sputum microbiota also associated with T2-low asthma phenotype, a subgroup of whom displayed elevations in lung inflammatory mediators and reduced sputum bacterial diversity. Differences in specific oral microbiota were more reflective of atopic status. After ICS treatment of patients with asthma, the compositional structure of sputum microbiota showed greater deviation from baseline in ICS nonresponders than in ICS responders. CONCLUSIONS: Novel associations of sputum and oral microbiota to immunologic features were observed in this cohort of subjects with or without ICS-naive mild asthma. These findings confirm and extend our previous report of reduced bronchial bacterial burden and compositional complexity in subjects with T2-high asthma, with additional identification of a T2-low subgroup with a distinct microbiota-immunologic relationship.
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