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Abdel-Aziz, M.I.* ; Hashimoto, S.* ; Neerincx, A.H.* ; Haarman, E.G.* ; Cecil, A. ; Lintelmann, J. ; Witting, M. ; Hauck, S. ; Kerssemakers, N.* ; Verster, J.C.* ; Bang, C.* ; Franke, A.* ; Dierdorp, B.S.* ; Dekker, T.J.* ; Metwally, N.K.A.* ; Duitman, J.W.* ; Lutter, R.* ; Gorenjak, M.* ; Toncheva, A.A.* ; Kheiroddin, P.* ; Harner, S.* ; Brandstetter, S.* ; Wolff, C.* ; Corcuera-Elosegui, P.* ; López-Fernández, L.* ; Perez-Garcia, J.* ; Almeida, M.M.* ; Sardón-Prado, O.* ; Pino-Yanes, M.* ; Potocnik, U.* ; Kabesch, M.* ; Vijverberg, S.J.H.* ; Kraneveld, A.D.* ; Maitland-van der Zee, A.H.*

Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation.

J. Allergy Clin. Immunol. 156:339-351 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
BACKGROUND: Childhood asthma has been linked to distinct metabolomic profiles. OBJECTIVE: To identify phenotypes (metabotypes) in children with moderate-to-severe asthma through integrative fecal and serum metabolome analysis. METHODS: Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step ≥3 were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomics profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity Network Fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells. RESULTS: Integrative fecal and serum metabolome analysis of 92 children with moderate-to-severe asthma (median age: 11.5 years, 34% female) revealed three metabotypes. Metabotype1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype2 had higher odds of asthma control, the highest percentage of children with ≥4 months of breastfeeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and with elevated serum acylcarnitines and ω-3 fatty acids. Metabotype3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity. CONCLUSIONS: Metabotypes in children with moderate-to-severe asthma are linked to asthma control, distinct fecal microbiota and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gut Microbiota ; Inflammatory Markers ; Metabotyping ; Moderate-to-severe Childhood Asthma ; Personalized Medicine
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Zeitschrift The journal of allergy and clinical immunology
Quellenangaben Band: 156, Heft: 2, Seiten: , Artikelnummer: 339-351 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Förderungen Spanish Ministry of Science, Innovation, and Universities
Ministry of Higher Education (Egypt)
Longfonds, Stichting Astma Bestrijding, and Amsterdam Public Health Institute (Netherlands)
Instituto de Salud Carlos III through Strategic Action for Health Research (AES) and European Community within the Active and Assisted Living Program framework
German Ministry of Education and Research (BMBF)
Ministry of Higher Education, Science and Innovation of the Republic of Slovenia (MVZI)
Netherlands Organisation for Health Research and Development (ZonMw)