Untargeted metabolomics profiling of childhood asthma: linking metabolic pattern to disease severity

Asthma is a heterogeneous inflammatory airway disorder associated with complex metabolic alterations. Despite significant advances in diagnosis and treatment, its prevalence and disease burden continue to rise, particularly among children. Recent research reveals that metabolic alterations play a crucial role in the disease development, severity, and treatment response. This study aimed to investigate dysregulation of serum metabolites in children with moderate-to-severe asthma compared with healthy controls using an untargeted metabolomic profiling approach. Hierarchical clustering and stratified analyses identified distinct metabolic signatures differentiating asthmatic patients from controls, with progressive changes reflecting increasing disease severity. Thirty-nine metabolites were found to be commonly dysregulated in moderate and severe asthma. Notably, adenosine and orotic acid were significantly upregulated, while 5-methoxytryptophol (5-MTX) was markedly downregulated, showing its lowest levels in severe asthma. Pathway enrichment analysis revealed significant disruptions in pyrimidine, amino acid, and urea cycle pathways. The identified metabolites and disrupted metabolic pathways may offer potential biomarkers of disease severity and provide insights to guide future therapeutic strategies. However, their utility in clinical practice as diagnostic or prognostic biomarkers across the full spectrum of asthma requires further validation in independent cohorts that include children with mild disease.