Integrative study of the upper and lower airway microbiome and transcriptome in asthma
Yoojin Chun, Anh Do, Galina Grishina, Alexander Grishin, Gang Fang, Samantha Rose, Chantal Spencer, Alfin Vicencio, Eric Schadt, Supinda Bunyavanich
Yoojin Chun, Anh Do, Galina Grishina, Alexander Grishin, Gang Fang, Samantha Rose, Chantal Spencer, Alfin Vicencio, Eric Schadt, Supinda Bunyavanich
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Research Article Microbiology Pulmonology

Integrative study of the upper and lower airway microbiome and transcriptome in asthma

Abstract

Relatively little is known about interactions between the airway microbiome and airway host transcriptome in asthma. Since asthma affects and is affected by the entire airway, studying the upper (e.g., nasal) and lower (e.g., bronchial) airways together represents a powerful approach to understanding asthma. Here, we performed a systematic, integrative study of the nasal and bronchial microbiomes and nasal and bronchial host transcriptomes of children with severe persistent asthma and healthy controls. We found that (a) the microbiomes and host transcriptomes of asthmatic children are each distinct by site (nasal versus bronchial); (b) among asthmatic children, Moraxella and Alloiococcus are hub genera in the nasal microbiome, while there are no hubs among bronchial genera; (c) bronchial Actinomyces is negatively associated with bronchial genes for inflammation, suggesting Actinomyces may be protective; (d) compared with healthy children, asthmatic children express more nasal genes for ciliary function and harbor more nasal Streptococcus; and (e) nasal genera such as Corynebacterium are negatively associated with significantly more nasal genes for inflammation in healthy versus asthmatic children, suggesting a potentially stronger protective role for such nasal genera in healthy versus asthmatic children. Our systematic, integrative study provides a window into host-microbiome associations in asthma.

Authors

Yoojin Chun, Anh Do, Galina Grishina, Alexander Grishin, Gang Fang, Samantha Rose, Chantal Spencer, Alfin Vicencio, Eric Schadt, Supinda Bunyavanich

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Figure 1

Study design and analytic flow.

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Study design and analytic flow. For each child with severe persistent as...
For each child with severe persistent asthma (n = 27), 4 matched samples were collected and profiled, including nasal transcriptome, nasal microbiome, bronchial transcriptome, and bronchial microbiome. For each healthy control (i.e., child without asthma, n = 27), samples for nasal transcriptome and nasal microbiome were collected and profiled; bronchial samples were not collected because bronchoscopy is not indicated in healthy children. The circled numbers, referred to as steps, represent the analytic steps taken in this systematic study. Among children with severe persistent asthma, we compared the nasal versus bronchial transcriptome (step 1), and the nasal versus bronchial microbiome (step 2). We also assessed positive and negative associations between genera abundances among nasal microbiota, among bronchial microbiota, and between nasal and bronchial microbiota in children with severe persistent asthma (step 2). Next, using the matched samples from these children with severe persistent asthma, we characterized associations between nasal transcriptome and nasal microbiota (step 3), as well as associations between bronchial transcriptome and bronchial microbiota (step 4). We then compared the nasal transcriptome of children with severe persistent asthma with that of healthy controls (step 5), as well as the nasal microbiome of children with severe persistent asthma with that of healthy controls (step 6). Finally, we characterized the associations between nasal transcriptome and nasal microbiota in healthy controls (step 7).