Perturbations in the airway microbiome are associated with type 2 asthma phenotype and severity.

Abstract

Airway microbiome has been linked to asthma heterogeneity, yet little is known about the associations between airway microbiota and type 2 (T2) asthma phenotype and severity. We aimed to determine the relationship of nasopharyngeal (NP) and induced sputum (IS) microbiota to the phenotypic features of T2 asthma. NP and IS samples from subjects with T2 mild-to-moderate asthma (n=23) and severe asthma (n=21) and healthy controls (n=16) were analyzed. Bacterial microbiota and functional profiles were compared. The correlation between microbial communities and clinical as well as inflammatory features was examined in asthmatics of two statuses. Differences in NP and IS microbiota were associated with T2 asthma phenotype. Alterations in NP microbiota were more reflective of T2 inflammation and severity, with additional stratification of a subgroup characterized by significant elevations in T2 inflammatory biomarkers and reductions in bacterial richness and diversity (P < .05). Burkholderia-Caballeronia-Paraburkholderia, Ralstonia and Rhodococcus were identified as hub taxa within NP microbial network in T2 severe asthma, which were prevalent in the entire airway and involved in bacterial functions including inflammatory and steroid responses (P < .05). The composition and diversity of IS microbiota were complex, with Veillonella as the most altered genus, showing an increase with increasing asthma severity. Our work revealed the significant associations of microbiota perturbations throughout the entire respiratory tract to the extent of T2 inflammation, phenotype and severity in T2 asthma. The specific taxa identified invite further mechanistic investigations to unravel their possibility as biomarkers and therapeutic targets for T2 severe asthma.