Association of corticosteroid inhaler type with saliva microbiome in moderate-to-severe pediatric asthma Background Metered dose inhalers (MDIs) and dry powder inhalers (DPIs) are common inhaled corticosteroid (ICS) inhaler devices. The difference in formulation and administration technique of these devices may influence oral cavity microbiota composition. We aimed to compare the saliva microbiome in children with moderate-to-severe asthma using ICS via MDIs versus DPIs. Methods Saliva samples collected from 143 children (6-17 yrs) with moderate-to-severe asthma across four European countries (the Netherlands, Germany, Spain, and Slovenia) as part of the SysPharmPediA cohort were subjected to 16S rRNA sequencing. Microbiome was compared using global diversity (α and β) between two groups of participants based on inhaler devices (MDI (n=77) and DPI (n=65)) and differential abundance was compared using the Analysis of Compositions of Microbiomes with the Bias Correction (ANCOM-BC) method. Results No significant difference was observed in α-diversity between the two groups. However, β-diversity analysis revealed significant differences between groups using both Bray-Curtis and weighted UniFrac methods (Adjusted p-value=0.015 and 0.044, respectively). Significant differential abundance between groups, with higher relative abundance in the MDI group compared to the DPI group, was detected at the family level [Carnobacteriaceae (Adjusted p=0.033)] and at the genus level [ Granulicatella (Adjusted p=0.021) and Aggregatibacter (Adjusted p=0.011)]. Conclusion Types of ICS devices are associated with different saliva microbiome composition in moderate-to-severe pediatric asthma. The causal relation between inhaler types and changes in saliva microbiota composition needs to be further evaluated, as well as whether this leads to different potential adverse effects in terms of occurrence and level of severity.