Association of Corticosteroid Inhaler Type with Saliva Microbiome in Moderate-to-Severe Pediatric Asthma
Amir Hossein Alizadeh Bahmani,
Mahmoud I. Abdel-Aziz,
Simone Hashimoto,
Corinna Bang,
Susanne Brandstetter,
Paula Corcuera-Elosegui,
Andre Franke,
Mario Gorenjak,
Susanne Harner,
Parastoo Kheiroddin,
Leyre López-Fernández,
Anne H. Neerincx,
Maria Pino-Yanes,
Uroš Potočnik,
Olaia Sardón-Prado,
Antoaneta A. Toncheva,
Christine Wolff,
Michael Kabesch,
Aletta D. Kraneveld,
Susanne J. H. Vijverberg,
Anke H. Maitland-van der Zee,
on behalf of the SysPharmPediA consortium
Affiliations
Amir Hossein Alizadeh Bahmani
Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Mahmoud I. Abdel-Aziz
Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Simone Hashimoto
Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Corinna Bang
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, D-24105 Kiel, Germany
Susanne Brandstetter
University Children’s Hospital Regensburg (KUNO), University of Regensburg, D-93049 Regensburg, Germany
Paula Corcuera-Elosegui
Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, 20014 San Sebastián, Spain
Andre Franke
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, D-24105 Kiel, Germany
Mario Gorenjak
Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
Susanne Harner
Department of Pediatric Pneumology and Allergy, University Children’s Hospital Regensburg (KUNO), D-93049 Regensburg, Germany
Parastoo Kheiroddin
Department of Pediatric Pneumology and Allergy, University Children’s Hospital Regensburg (KUNO), D-93049 Regensburg, Germany
Leyre López-Fernández
Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, 20014 San Sebastián, Spain
Anne H. Neerincx
Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Maria Pino-Yanes
Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), 38200 Santa Cruz de Tenerife, Spain
Uroš Potočnik
Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
Olaia Sardón-Prado
Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, 20014 San Sebastián, Spain
Antoaneta A. Toncheva
Department of Pediatric Pneumology and Allergy, University Children’s Hospital Regensburg (KUNO), D-93049 Regensburg, Germany
Christine Wolff
Department of Pediatric Pneumology and Allergy, University Children’s Hospital Regensburg (KUNO), D-93049 Regensburg, Germany
Michael Kabesch
Department of Pediatric Pneumology and Allergy, University Children’s Hospital Regensburg (KUNO), D-93049 Regensburg, Germany
Aletta D. Kraneveld
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
Susanne J. H. Vijverberg
Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Anke H. Maitland-van der Zee
Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Background/Objectives: 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. The 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)]. Conclusions: Types of ICS devices are associated with different saliva microbiome compositions 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.
