Urinary Metabolomic Profiling Reveals Biological Pathways and Predictive Signatures Associated with Childhood Asthma

BACKGROUND: Despite considerable efforts, the pathogenic mechanisms of asthma are still incompletely understood, due to its heterogeneous nature. However, metabolomics can offer a global view of a biological system, making it a valuable tool for further elucidation of mechanisms and biomarker discovery in asthma. METHODS: GC-MS–based metabolomic analysis was conducted for comparison of urine metabolic profiles between asthmatic children (n=30) and healthy controls (n=30). RESULTS: An orthogonal projections to latent structures discriminant–analysis model revealed a clear separation of the asthma and control groups (R(2)(x)=0.137, R(2)(y)=0.947, Q(2)=0.82). A total of 20 differential metabolites were identified as discriminant factors, of which eleven were significantly increased and nine decreased in the asthma group compared to the control group. Pathway-enrichment analysis based on these differential metabolites indicated that sphingolipid metabolism, protein biosynthesis, and citric acid cycle were strongly associated with asthma. Among the identified metabolites, 2-hydroxybutanoic acid showed excellent discriminatory performance for distinguishing asthma from healthy controls, with an AUC of 0.969. CONCLUSION: Our study revealed significant changes in the urine metabolome of asthma patients. Several perturbed pathways (eg, sphingolipid metabolism and citric acid cycle) may be related to asthma pathogenesis, and 2-hydroxybutanoic acid could serve as a potential biomarker for asthma diagnosis.