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).