Integrative analysis of upper and lower airway microbial communities identifies its association with T2-High asthma phenotype and severity (PRJCA020718)
Airway microbiome has been linked to T2-high asthma pathogenesis and heterogeneity, but it remains unknown how the effect on T2-high asthma phenotype and severity. We systematically studied nasopharyngeal (nasal) and induced-sputum (sputum) microbiome in T2-high mild-to-moderate asthma (MMA), T2-high severe asthma (SA) and health control (HC). The goal of this study was to explore the characteristics of nasal and sputum microbiota in patients with T2-high MMA, SA and HC, and determine the relationship of nasal and sputum microbiota to the phenotypic features and severity of T2-high asthma. We collected nasal and induced-sputum samples from MMA group (n=23), SA group (n=21) and HC groups (n=16) followed by 16s rRNA sequencing. Microbial profiles and microbiome function were analyzed and compared among these three groups. Relationship to clinical and inflammatory features was examined for two subgroups of asthmatics, including T2 inflammation biomarkers, cytokines, immune cell counts and lung function. Sputum and nasal microbiota were compositional and functionally distinct. An increase of Veillonella in sputum was particularly associated with an increase in asthma severity. Nasal microbiota exhibited stratification with asthma state concordant with elevated level of T2 inflammatory biomarkers. Alterations in nasal microbiota are more reflective of asthma status and influence the degree of T2 inflammation, while sputum microbiota are reflective of inflammatory response in the lower respiratory tract. Protective genera Lactobacillus and Corynebacterium were decreased in asthmatics whereas commensals Burkholderia-Caballeronia-Paraburkholderia, Ralstonia and Rhodococcus were enriched in the whole airway of T2-high asthma patients regardless of severity state. They were hub genera in nasal microbiota specifically enriched in severe asthma and positively associated with T2 inflammation and steroid degradation. Microbial co-exclusion and co-occurrence network analysis revealed the novel upper-lower airway bacterial association related to the development of asthma severity. Here we report that the dynamic alteration in whole airway microbiome was related to asthma exacerbation. Nasal microbiome was indicative of a shift in bacterial community structure related to asthma phenotype and severity, with additional identification of a subgroup of T2-high asthma showing higher risk of asthma progression. We identified novel cooperative and competitive associations among genera promoting the development of asthma via mediating inflammatory and steroid responses. These findings provide more insights into the influence of lung microbial dysbiosis to the inception and progress of T2-high asthma.