Nasopharyngeal microbiota in children is associated with severe asthma exacerbations.

Background The respiratory microbiome has been associated with the etiology and disease course of asthma. Objective This study assessed the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality and viral infection. Methods A cross-sectional study was performed among children aged 2-18 years admitted to the medium (MCU; n=84) or intensive care (ICU; n=78) with an asthma exacerbation. For case-control analyses, we matched all cases aged 2-6 years (n=87) to controls in a 1:2 ratio. Controls were participants of either a prospective case-control study or a longitudinal birth cohort (n=182). The nasopharyngeal microbiome was characterized by 16S-rRNA-gene sequencing. Results Cases showed higher Shannon diversity (ICU and MCU combined; p=0.002) and a distinct microbial community composition when compared to controls (PERMANOVA R2=1.9%, p<0.001). We observed significantly higher abundance of Staphylococcus and ‘oral’ taxa, including Neisseria, Veillonella and Streptococcus spp. and lower abundance of Dolosigranulum pigrum, Corynebacterium and Moraxella spp. (MaAsLin2, q<0.25) in cases versus controls. Furthermore, Neisseria abundance was associated with more severe disease (ICU vs MCU MaAslin2 p=0.03, q=0.30). Neisseria spp. abundance was also related with fine particulate matter exposure, whereas Haemophilus and Streptoccocus abundance was related with recent inhalation corticosteroid use. We observed no correlations with viral infection. Conclusion Our results demonstrate that children admitted with asthma exacerbations harbor a microbiome characterized by overgrowth of Staphylococcus and ‘oral’ microbes, and an underrepresentation of beneficial niche-appropriate commensals. Several of these associations may be explained by (environmental or medical) exposures, although cause-consequence relationships remain unclear and requires further investigations.