TY - JOUR
T1 - Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways, and Exacerbation Risk
AU - Abdel-Aziz, Mahmoud I
AU - Thorsen, Jonathan
AU - Hashimoto, Simone
AU - Vijverberg, Susanne J H
AU - Neerincx, Anne H
AU - Brinkman, Paul
AU - van Aalderen, Wim
AU - Stokholm, Jakob
AU - Rasmussen, Morten Arendt
AU - Roggenbuck-Wedemeyer, Michael
AU - Vissing, Nadja H
AU - Mortensen, Martin Steen
AU - Brejnrod, Asker Daniel
AU - Fleming, Louise J
AU - Murray, Clare S
AU - Fowler, Stephen J
AU - Frey, Urs
AU - Bush, Andrew
AU - Singer, Florian
AU - Hedlin, Gunilla
AU - Nordlund, Björn
AU - Shaw, Dominick E
AU - Chung, Kian Fan
AU - Adcock, Ian M
AU - Djukanovic, Ratko
AU - Auffray, Charles
AU - Bansal, Aruna T
AU - Sousa, Ana R
AU - Wagers, Scott S
AU - Chawes, Bo Lund
AU - Bønnelykke, Klaus
AU - Sørensen, Søren Johannes
AU - Kraneveld, Aletta D
AU - Sterk, Peter J
AU - Roberts, Graham
AU - Bisgaard, Hans
AU - Maitland-van der Zee, Anke H
N1 - Funding Information: U-BIOPRED has received funding from the Innovative Medicines Initiative Joint Undertaking under FP7 Health grant agreement 115010, resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions (www.imi.europa.eu). M.I.A.-A. has received a full scholarship from the Ministry of Higher Education of the Arab Republic of Egypt (2015/2016). Publisher Copyright: Copyright © 2023 by the American Thoracic Society.
PY - 2023/7/15
Y1 - 2023/7/15
N2 - 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 b-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-b (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.
AB - 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 b-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-b (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.
KW - asthma
KW - microbiota
KW - phenotype
KW - precision medicine
KW - wheezing
UR - http://www.scopus.com/inward/record.url?scp=85164844622&partnerID=8YFLogxK
U2 - https://doi.org/10.1164/rccm.202211-2107OC
DO - https://doi.org/10.1164/rccm.202211-2107OC
M3 - Article
C2 - 37163754
SN - 1073-449X
VL - 208
SP - 142
EP - 154
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 2
ER -