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Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic
Mahmoud I Abdel-Aziz1,2,3,4, Jonathan Thorsen5,6, Simone Hashimoto1,7,2,3
1Department of Pulmonary Medicine and.
Insights
Childhood asthma and wheezing are linked to distinct oropharyngeal microbial communities. These four clusters show varied clinical traits and link to airway remodeling pathways, offering new treatment avenues.
Area of Science:
- Pediatric respiratory medicine
- Microbiome research
- Immunology
Background:
- Airway microbial imbalances are reported in children with preschool wheezing and school-age asthma.
- Understanding these imbalances is crucial for identifying distinct disease phenotypes.
Purpose of the Study:
- To identify distinct clusters within children experiencing asthma or wheezing based on their oropharyngeal microbiota profiles.
- To correlate these microbial clusters with clinical characteristics and exacerbation risk.
Main Methods:
- 16S ribosomal RNA gene sequencing was used to characterize oropharyngeal microbiota in 241 children from the U-BIOPRED cohort.
- Unsupervised hierarchical clustering identified four distinct taxa-driven clusters.
- Blood transcriptome analysis assessed transcriptomic pathway enrichment.
Main Results:
- Four oropharyngeal microbiota clusters dominated by Streptococcus, Veillonella, Rothia, and Haemophilus were identified.
- Clusters differed significantly in atopic dermatitis, grass pollen sensitization, lung function (FEV1), and asthma exacerbation frequency.
- The Veillonella cluster showed higher allergic burden and exacerbation rates, with elevated TGF-β signaling.
Conclusions:
- Oropharyngeal microbiota profiling in children with asthma/wheezing reveals four distinct phenotypes associated with exacerbation risk.
- These phenotypes correlate with specific transcriptomic pathways involved in airway remodeling.
- Further research into the oropharyngeal microbiome may uncover novel pathophysiological insights and therapeutic strategies for pediatric asthma.
Abstract:
Rationale: Children with preschool wheezing or school-age asthma are reported to have airway microbial imbalances. Objectives: To identify clusters in children with asthma or wheezing using oropharyngeal microbiota profiles. Methods: Oropharyngeal swabs from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) pediatric asthma or wheezing cohort were characterized using 16S ribosomal RNA gene sequencing, and unsupervised hierarchical clustering was performed on the Bray-Curtis β-diversity. Enrichment scores of the Molecular Signatures Database hallmark gene sets were computed from the blood transcriptome using gene set variation analysis. Children with severe asthma or severe wheezing were followed up for 12-18 months, with assessment of the frequency of exacerbations. Measurements and Main Results: Oropharyngeal samples from 241 children (age range, 1-17 years; 40% female) revealed four taxa-driven clusters dominated by Streptococcus, Veillonella, Rothia, and Haemophilus. The clusters showed significant differences in atopic dermatitis, grass pollen sensitization, FEV1% predicted after salbutamol, and annual asthma exacerbation frequency during follow-up. The Veillonella cluster was the most allergic and included the highest percentage of children with two or more exacerbations per year during follow-up. The oropharyngeal clusters were different in the enrichment scores of TGF-β (transforming growth factor-β) (highest in the Veillonella cluster) and Wnt/β-catenin signaling (highest in the Haemophilus cluster) transcriptomic pathways in blood (all q values <0.05). Conclusions: Analysis of the oropharyngeal microbiota of children with asthma or wheezing identified four clusters with distinct clinical characteristics (phenotypes) that associate with risk for exacerbation and transcriptomic pathways involved in airway remodeling. This suggests that further exploration of the oropharyngeal microbiota may lead to novel pathophysiologic insights and potentially new treatment approaches.
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