Metabotypes are linked to uncontrolled childhood asthma, gut microbiota, and systemic inflammation.
Authors
Mahmoud I Abdel-Aziz, Simone Hashimoto, Anne H Neerincx, Eric G Haarman, Alexander Cecil, Jutta Lintelmann, Michael Witting, Stefanie M Hauck, Nikki Kerssemakers, Joris C Verster, Corinna Bang, Andre Franke, Barbara S Dierdorp, Tamara Dekker, Nariman K A Metwally, Jan Willem Duitman, René Lutter, Mario Gorenjak, Antoaneta A Toncheva, Parastoo Kheiroddin, Susanne Harner, Susanne Brandstetter, Christine Wolff, Paula Corcuera-Elosegui, Leyre López-Fernández, Javier Perez-Garcia, Mario Martin-Almeida, Olaia Sardón-Prado, Maria Pino-Yanes, Uroš Potočnik, Michael Kabesch, Susanne J H Vijverberg, Aletta D Kraneveld, Anke H Maitland-van der Zee
Year of publication
2025Journal
J ALLERGY CLIN IMMUNVolume
-Issue
-Abstract
Background
Childhood asthma has been linked to distinct metabolomic profiles.
Objective
We sought 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 or higher were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomic 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 3 metabotypes. Metabotype 1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype 2 had higher odds of asthma control, the highest percentage of children with 4 or more months of breast-feeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and elevated serum acylcarnitines and ω-3 fatty acids. Metabotype 3 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.