Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma

详细信息    查看全文

• 作者：Yvonne J. Huang MD^a ; Craig E. Nelson PhD^b ; Eoin L. Brodie PhD^c ; Todd Z. DeSantis MS^c ; Marshall S. Baek BS^d ; Jane Liu MS^a ; Tanja Woyke PhD^e ; Martin Allgaier PhD^d ; Jim Bristow MD^e ; Jeanine P. Wiener-Kronish MD^d ; E. Rand Sutherland MD ; MPH^f ; Tonya S. King PhD^g ; Nikolina Icitovic MAS^g ; Richard J. Martin MD^f ; William J. Calhoun MD^h ; Mario Castro MDⁱ ; Loren C. Denlinger MD ; PhD^j ; Emily DiMango MD^k ; Monica Kraft MD^l ; Stephen P. Peters MD ; PhD^m ; Stephen I. Wasserman MDⁿ ; Michael E. Wechsler MD^o ; Homer A. Boushey MD^a ; Susan V. Lynch PhD^p ; ^{susan.lynch@ucsf.edu} ; National Heart ; Lung ; Blood Institute’ ; s Asthma Clinical Research Network^*
• 关键词：Microbiome ; bacteria ; asthma ; 16S ribosomal RNA ; PhyloChip
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：127
• 期：2
• 页码：372-381.e3
• 全文大小：840 K

文摘

Background

Improvement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present.

Objective

We sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria.

Methods

In this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements.

Results

Compared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness.

Conclusion: The composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.