Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment

被引：221

作者：

Durack, Juliana ^{[1
]}

Lynch, Susan V. ^{[1
]}

Nariya, Snehal ^{[2
]}

Bhakta, Nirav R. ^{[3
]}

Beigelman, Avraham ^{[4
]}

Castro, Mario ^{[4
,5
]}

Dyer, Anne-Marie ^{[6
]}

Israel, Elliot ^{[7
]}

Kraft, Monica ^{[8
]}

Martin, Richard J. ^{[9
]}

Mauger, David T. ^{[6
]}

Rosenberg, Sharon R. ^{[10
]}

Sharp-King, Tonya ^{[6
]}

White, Steven R. ^{[11
]}

Woodruff, Prescott G. ^{[3
]}

Avila, Pedro C. ^{[10
]}

Denlinger, Loren C. ^{[12
]}

Holguin, Fernando ^{[13
]}

Lazarus, Stephen C. ^{[3
]}

Lugogo, Njira ^{[14
]}

Moore, Wendy C. ^{[15
]}

Peters, Stephen P. ^{[15
]}

Que, Loretta ^{[14
]}

Smith, Lewis J. ^{[10
]}

Sorkness, Christine A. ^{[12
]}

Wechsler, Michael E. ^{[9
]}

Wenzel, Sally E. ^{[13
]}

Boushey, Homer A. ^{[3
]}

Huang, Yvonne J. ^{[2
]}

机构：

[1] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA

[2] Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI USA

[3] Univ Calif San Francisco, Dept Med, San Francisco, CA USA

[4] Washington Univ, Div Pediat, Sch Med, St Louis, MO 63130 USA

[5] Washington Univ, Div Pulm & Crit Care Med, Sch Med, St Louis, MO 63130 USA

[6] Penn State Univ, Dept Publ Hlth Sci, Hershey, PA USA

[7] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[8] Univ Arizona, Hlth Sci, Tucson, AZ USA

[9] Natl Jewish Hosp, Dept Med, Denver, CO USA

[10] Northwestern Univ, Dept Med, Chicago, IL 60611 USA

[11] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[12] Univ Wisconsin Madison, Dept Med, Madison, WI USA

[13] Univ Pittsburgh, Asthma Inst, UPMC UPSOM, Pittsburgh, PA USA

[14] Duke Univ, Sch Med, Duke Asthma Allergy & Airway Ctr, Durham, NC 27706 USA

[15] Wake Forest Sch Med, Winston Salem, NC USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2017年 / 140卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Asthma; atopy; microbiome; corticosteroids; 16S ribosomal RNA; bacteria; T(H)2 inflammation; three-gene mean; metabolic pathways; short-chain fatty acids; HAEMOPHILUS-INFLUENZAE; AIRWAY MICROBIOME; EXPRESSION; INFECTION; EOSINOPHILS; COMMUNITIES; DIVERSITY; SECRETION; DISEASE; MODELS;

D O I：

10.1016/j.jaci.2016.08.055

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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 communitylevel 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 inmembers 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.

引用

页码：63 / 75

页数：13

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