TY - JOUR
T1 - Distinct associations of sputum and oral microbiota with atopic, immunologic, and clinical features in mild asthma
AU - National Heart, Lung, and Blood Institute's AsthmaNet
AU - Durack, Juliana
AU - Christian, Laura S.
AU - Nariya, Snehal
AU - Gonzalez, Jeanmarie
AU - Bhakta, Nirav R.
AU - Ansel, K. Mark
AU - Beigelman, Avraham
AU - Castro, Mario
AU - Dyer, Anne Marie
AU - Israel, Elliot
AU - Kraft, Monica
AU - Martin, Richard J.
AU - Mauger, David T.
AU - Peters, Stephen P.
AU - Rosenberg, Sharon R.
AU - Sorkness, Christine A.
AU - Wechsler, Michael E.
AU - Wenzel, Sally E.
AU - White, Steven R.
AU - Lynch, Susan V.
AU - Boushey, Homer A.
AU - Huang, Yvonne J.
N1 - Funding Information:
The analyses performed in this study were supported by National Heart, Lung, and Blood Institute AsthmaNet (grant no. U10HL098107 ), and by National Institutes of Health grant numbers R01AI129958 and R03HL13831 (both to Y.J.H.).
Funding Information:
Disclosure of potential conflict of interest: N. R. Bhakta, K. M. Ansel, A. Beigelman, S. P. Peters, C. A. Sorkness, and S. R. White report grants from the National Institutes of Health (NIH). M. Castro reports grants from the NIH, the American Lung Association (ALA), Boehringer Ingelheim, Genentech, GlaxoSmithKline (GSK), Invion, Sanofi-Aventis, and Vectura and personal fees from Aviragen, Boehringer Ingelheim, Boston Scientific, Elsevier, Genentech, GSK, Holaira, and Teva. E. Israel reports personal fees from AstraZeneca, Novartis, Philips, Respironics, Regeneron Pharmaceuticals, Research in Real Life, Teva Specialty Pharmaceuticals, Bird Rock Bio, Nuvelution, Pharmaceuticals, Vitaeris, Inc, Sanofi, Merck, Entrinsic Health Solutions, and GSK; nonfinancial support from Boehringer Ingelheim, GSK, Merck, Sunovion, and Teva Specialty Pharmaceuticals; and grants from Sanofi, Genentech, and Boehringer Ingelheim. M. Kraft reports grants from the NIH, Chiesi, and Sanofi and personal fees from Teva Pharmaceuticals, Astra Zeneca, Food and Drug Administration LABA Trials Joint DSMB, and Elsevier. R. J. Martin reports grants from the NIH; personal fees from AstraZeneca, PMD Healthcare, and Respiratory Effectiveness Group; and other fees from MedImmune and CHiesi FarmaceuticiSpA. D. T. Mauger reports grants from the NIH and nonfinancial support from GSK, Merck, and Boehringer Ingelheim. 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, GSK, Tunitas, and Gliacure. S. E. Wenzel has received grants from Sanofi, Genentech, AstraZeneca, GSK, and Boehringer Ingelheim and has received personal fees from AstraZeneca, Aerocrine, GSK, Actelion, and Boehringer Ingelheim. S. V. Lynch reports grants from NIH/National Institute of Allergy and Infectious Diseases (NIAID), NIH/National Institute of Child Health and Human Development, NIH/National Institute on Drug Abuse, Broad Foundation, Sloan Foundation, Pfizer, Inc, Gilead Sciences, and Janssen; personal fees from Janssen, Boston Consulting Group, Regeneron, MedImmune, and Siolta Therapeutics; has a patent reductive prodrug cancer chemotherapy (Stan449-PRV) issued, a patent Combination antibiotic and antibody therapy for the treatment of Pseudomonas aeruginosa infection (WO 2010091189 A1) with royalties paid to KaloBios, Inc, a patent therapeutic microbial consortium for induction of immune tolerance with royalties paid to Siolta Therapeutics, a patent systems and methods for detecting antibiotic resistance (WO 2012027302 A3) issued, a patent nitroreductase enzymes (US 7687474 B2) issued, a patent sinusitis diagnostics and treatments (WO 2013155370 A1) issued, and a patent methods and systems for phylogenetic analysis (US 20120264637 A1) issued; and has cofounded Siolta Therapeutics and is currently a board member, paid consultant for the company, and owns 25% stock. H. A. Boushey has received grants including travel and lodging compensation from the NIH/NHLBI and the NIH/NIAID; has received royalty payments from the McGraw-Hill Companies; and is a consultant for Siolta Therapeutics, Inc, of San Francisco, Calif. Y. J. Huang has received grants from the NIH, the Michigan Institute of Health and Clinical Research, and travel compensation for lectures and committee work with the National Academies of Science, the American Academy of Allergy, Asthma & Immunology, and the European Academy of Allergy, Asthma, and Clinical Immunology. The rest of the authors declare that they have no relevant conflicts of interest.
Publisher Copyright:
© 2020 American Academy of Allergy, Asthma & Immunology
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085191100&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085191100&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2020.03.028
DO - 10.1016/j.jaci.2020.03.028
M3 - Article
C2 - 32298699
AN - SCOPUS:85085191100
VL - 146
SP - 1016
EP - 1026
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 5
ER -