Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways, and Exacerbation Risk.

Autor:	Abdel-Aziz MI; Department of Pulmonary Medicine and.; Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.; Amsterdam Public Health, Amsterdam, the Netherlands.; Department of Clinical Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt., Thorsen J; Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, and., Hashimoto S; Department of Pulmonary Medicine and.; Department of Paediatric Pulmonary Medicine, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.; Amsterdam Public Health, Amsterdam, the Netherlands., Vijverberg SJH; Department of Pulmonary Medicine and.; Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.; Amsterdam Public Health, Amsterdam, the Netherlands., Neerincx AH; Department of Pulmonary Medicine and.; Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.; Amsterdam Public Health, Amsterdam, the Netherlands., Brinkman P; Department of Pulmonary Medicine and.; Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.; Amsterdam Public Health, Amsterdam, the Netherlands., van Aalderen W; Department of Paediatric Pulmonary Medicine, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Stokholm J; Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.; Department of Food Science, University of Copenhagen, Frederiksberg, Denmark., Rasmussen MA; Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.; Department of Food Science, University of Copenhagen, Frederiksberg, Denmark., Roggenbuck-Wedemeyer M; Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.; Novozymes, Bagsvaerd, Denmark., Vissing NH; Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital., Mortensen MS; Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark., Brejnrod AD; Section of Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark., Fleming LJ; National Heart and Lung Institute, Imperial College London, London, United Kingdom.; Royal Brompton and Harefield NHS Trust, London, United Kingdom., Murray CS; Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.; Manchester Academic Health Science Centre and National Institute for Health and Care Research Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom., Fowler SJ; Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.; Manchester Academic Health Science Centre and National Institute for Health and Care Research Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom., Frey U; University Children's Hospital Basel, University of Basel, Basel, Switzerland., Bush A; National Heart and Lung Institute, Imperial College London, London, United Kingdom.; Royal Brompton and Harefield NHS Trust, London, United Kingdom., Singer F; Division of Paediatric Pulmonology and Allergology, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.; Division of Paediatric Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Hedlin G; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden., Nordlund B; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden., Shaw DE; National Institute for Health and Care Research Respiratory Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom., Chung KF; National Heart and Lung Institute, Imperial College London, London, United Kingdom.; Royal Brompton and Harefield NHS Trust, London, United Kingdom., Adcock IM; National Heart and Lung Institute, Imperial College London, London, United Kingdom.; Royal Brompton and Harefield NHS Trust, London, United Kingdom., Djukanovic R; National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and Clinical and Experimental Sciences and Human Development and Health, University of Southampton, Southampton, United Kingdom., Auffray C; European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBL-INSERM, Lyon, France., Bansal AT; Acclarogen Ltd., St. John's Innovation Centre, Cambridge, United Kingdom., Sousa AR; Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom., Wagers SS; BioSci Consulting, Maasmechelen, Belgium; and., Chawes BL; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, and., Bønnelykke K; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, and., Sørensen SJ; Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark., Kraneveld AD; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands., Sterk PJ; Department of Pulmonary Medicine and.; Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands., Roberts G; National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and Clinical and Experimental Sciences and Human Development and Health, University of Southampton, Southampton, United Kingdom., Bisgaard H; Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital., Maitland-van der Zee AH; Department of Pulmonary Medicine and.; Department of Paediatric Pulmonary Medicine, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.; Amsterdam Public Health, Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2023 Jul 15; Vol. 208 (2), pp. 142-154.
DOI:	10.1164/rccm.202211-2107OC
Abstrakt:	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, FEV 1 % 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.
Databáze:	MEDLINE
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