Introduction
Severe asthma is a heterogeneous condition that can be differentiated into clinical, and molecular inflammatory phenotypes (1). The severe eosinophilic asthma cluster is the most established inflammatory phenotype linked to Type 2 inflammation driven by cytokines such as IL-4, IL-5 and IL-13 (2). On the other hand, the neutrophilic inflammatory phenotype characterized by sputum neutrophilia is associated with Type 1 inflammatory pathways and inflammasome activation (3). While there has been a link between inflammasome activation and neutrophil airway recruitment in asthma (4), the mechanism driving neutrophil recruitment and activation remains unclear. Because of the ability of airway microbial organisms to induce inflammatory responses, the complex lung microbiome may contribute to clinical and inflammatory phenotypes of asthma (5, 6).
Detailed analysis of the microbial community composition in asthma has been made possible by using culture-independent techniques such as 16S ribosomal RNA microarray and PCR. Proteobacteria families are enriched in airway microbiota of asthma patients (7) and have been associated with airway hyperresponsiveness and worsening asthma control (8). Streptococcus pneumoniae, Moraxella catarrhalis (9, 10), andHaemophilus influenzae (7, 9, 11) have been reported in patients with stable asthma. Neutrophilic asthma has been associated with enriched Proteobacteria (12), including Moraxella andHaemophilus (13), and in particular Haemophilus influenzae(12). Reduced sputum bacterial diversity has been reported in neutrophilic asthma as compared with other asthma phenotypes (12, 13).
For the first time, we have undertaken a metagenomic whole genome sequencing approach of induced sputum from patients with asthma that has the added advantage of providing an in-depth characterization and insights into the microbiome down to the species level in order to understand the relationship between airway dysbiosis and airway inflammation. We have examined the effect of asthma severity and granulocytic inflammation on the abundance of microbial species. We also examined the relationship of the molecular phenotype of asthma to the bacterial species abundance that provides the potential links between these species and the host immunological and inflammatory responses (14).