Metabolomics in Childhood Asthma - a Promising Tool to Meet Various Clinical Needs

Abstract

Purpose of review: The aim of our review is to summarize the available literature where metabolomics was used in studies on childhood asthma, and to find metabolites that are diagnostic biomarker candidates in childhood asthma. Moreover, the review also describes studies related to metabo-endotypes and heterogeneity of childhood asthma, severity of the disease, and response to drug treatment.

Recent findings: Metabolomics has opened up new perspectives in childhood asthma investigation. Based on the available literature, we found nine metabolites that demonstrated the highest diagnostic potential for differentiation between children with asthma and healthy controls: adenine, adenosine, benzoic acid, hypoxanthine, p-cresol, taurocholate, threonine, tyrosine, and 1-methyl nicotinamide. Many of the identified metabolites are closely associated with inflammatory processes responsible for asthma. Metabolomic analysis also contributed to characterizing new asthma endotypes highlighting the heterogeneity of pediatric asthma. Metabolomics can bring about valuable insights, which, when integrated with other omic disciplines, can facilitate the diagnosis and management of childhood asthma and the search for new biomarkers of the disease. Improvements in the detection of asthma in preschool children, including asthma endotypes, will ease application of proper treatment and enable elimination of unnecessary test treatment of corticosteroids in young patients.

Keywords: Biomarkers; Metabo-endotypes; Metabolites; Pediatric asthma.

Fig. 1

Summary of literature search for reviewed articles. Created in BioRender.com

Fig. 2

Metabolic pathways and their involvement in childhood asthma pathogenesis based on performed metabolomic studies. The diagram illustrates the interactions between key metabolites identified as discriminative features in childhood asthma metabolomic studies. Three main metabolic groups are highlighted: the purine pathway (including adenine, adenosine, and hypoxanthine), gut microbiota metabolites (p-cresol and taurocholate), and amino acids with their derivatives (threonine and tyrosine). Arrows indicate metabolic relationships and physiological effects. Cellular stress initiates ATP release, leading to increased adenine levels, which shows anti-inflammatory properties. Elevated adenosine levels enhance mast cell degranulation, contributing to bronchoconstriction. Hypoxanthine, through xanthine oxidase activity, generates reactive oxygen species (ROS), exacerbating airway inflammation. Gut microbiota-derived metabolites demonstrate variable effects: p-cresol shows inconsistent levels across studies, while increased taurocholate exhibits anti-inflammatory properties through FXR activation. Among amino acids, decreased threonine levels may impair lymphocyte proliferation and tyrosine shows variable levels affecting p-cresol production. Color coding indicates metabolite level changes in asthmatic children: pink (↑) represents increased levels, blue (↓) indicates decreased levels, and yellow (↑↓) shows variable levels reported across different studies. Green boxes represent physiological processes

Fig. 3

Overview illustrating possible clinical utility of metabolomic studies in childhood asthma. Created with BioRender.com