Reciprocal fungal and bacterial microbiota in airways of patients with T2-high associated asthma

The relationship between asthma, atopy and underlying type 2 (T2) airway inflammation is complex. While the airway microbiome clearly differs in asthmatic patients, microbial markers that can discriminate T2-High and T2-Low asthma are incompletely identified. Further, a low bronchial bacterial burden recently identified in T2-High asthmatics has led to speculation that this group might harbor a higher fungal load. In this study, we investigated the fungal diversity across asthmatics and associated atopy and type 2 inflammation. Patients in the T2-High cohort had a higher fungal diversity compared to T2-Low patients; key fungal genera enriched in the former group included Galactomyces, Scolecobasidium, and Callistosporium. Using weighted correlation network analyses, we identified significant positive associations between specific fungal modules and forced expiratory volume (FEV1), fractional exhaled nitric oxide (FeNO), and BAL-eosinophils in the T2-High cohort. Examination of interkingdom co-occurrence patterns between bacterial and fungal taxa among T2 subsets demonstrated significant co-association of between the bacterial genera Prevotella and Actinomyces, and the fungal genera Saccharomyces and Galactomyces. Significant correlation was observed between predicted bacterial functional genes involved in nitrogen, bile-acid metabolism, calcium signaling and clinical parameters such as corticosteroid use, FEV1, and FeNO. This study demonstrates 1) a reciprocal relationship between fungal and bacterial microbiota in T2-High and T2-Low asthma, 2) significant co-association between bacterial and fungal genera, and 3) correlation between predicted bacterial functional gene abundances and clinical parameters. Both the fungal and bacterial microbiota may potentially be used in the future for both diagnosis and treatment of select asthma phenotypes.