BackgroundAirway 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. ObjectiveTo determine the relationship of nasopharyngeal (NP) and induced sputum (IS) microbiota to the phenotypic features of T2 asthma. MethodsNP and IS samples from subjects with T2 mild-to-moderate asthma (n = 23), subjects with 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 and inflammatory features was evaluated in individuals with asthma of 2 statuses. ResultsDifferences 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, having an increase with increasing asthma severity. ConclusionOur 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.
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