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Abdel-Aziz, MI; Thorsen, J; Hashimoto, S; Vijverberg, SJH; Neerincx, AH; Brinkman, P; van, Aalderen, W; Stokholm, J; Rasmussen, MA; Roggenbuck-Wedemeyer, M; Vissing, NH; Mortensen, MS; Brejnrod, AD; Fleming, LJ; Murray, CS; Fowler, SJ; Frey, U; Bush, A; Singer, F; Hedlin, G; Nordlund, B; Shaw, DE; Chung, KF; Adcock, IM; Djukanovic, R; Auffray, C; Bansal, AT; Sousa, AR; Wagers, SS; Chawes, BL; Bønnelykke, K; Sørensen, SJ; Kraneveld, AD; Sterk, PJ; Roberts, G; Bisgaard, H; Maitland-van, der, Zee, AH.
Oropharyngeal Microbiota Clusters in Children with Asthma/Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways and Exacerbations Risk.
Am J Respir Crit Care Med. 2023; Doi: 10.1164/rccm.202211-2107OC
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Singer Florian

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RATIONALE: Children with preschool wheezing or school-age asthma are reported to have airway microbial imbalances. OBJECTIVE: To identify clusters in children with asthma or wheezing using oropharyngeal microbiota profiles. METHODS: Oropharyngeal swabs, from the Unbiased BIOmarkers for the Prediction of REspiratory Disease outcomes pediatric asthma/wheezing cohort, were characterized by 16S rRNA gene sequencing and unsupervised hierarchical clustering was performed on the Bray-Curtis β-diversity. Enrichment scores (ESs) of the MSigDB 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 assessing the frequency of exacerbations. MEASUREMENTS AND MAIN RESULTS: Oropharyngeal samples of 241 children (age range: 1-17 years, 40% female) revealed 4 taxa-driven clusters dominated by Streptococcus, Veillonella, Rothia and Haemophilus, respectively. The clusters showed significant differences in atopic dermatitis, grass pollen sensitization, FEV1 % predicted post-salbutamol, and the annual asthma exacerbation frequency during follow-up. The Veillonella-cluster was the most allergic and included highest percentage of children with ≥2 exacerbations/year during follow-up. The oropharyngeal clusters were different in the ESs of transforming growth factor β (highest in Veillonella-cluster) and Wnt/β-Catenin signaling (highest in Haemophilus-cluster) transcriptomic pathways in blood (all q-values < 0.05). CONCLUSION: The analysis of the oropharyngeal microbiota of children with asthma/wheezing identified four clusters with distinct clinical characteristics (phenotypes) that associate with exacerbations' risk and transcriptomic pathways involved in airway remodeling. This suggests that further exploration of the oropharyngeal microbiota may lead to novel pathophysiological insights and potentially new treatment approaches.

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