Metabolomic biomarkers and altered phenylalanine metabolic pathway in preschool children with atopic dermatitis - A pilot study.

Abstract

Background Atopic dermatitis (AD) has high prevalence in children. Current AD diagnosis and management focuses only on clinical phenotypes, but do not explore the endophenotypes, which are more important because they are a series of biomarkers linking clinical phenotype and genotype Aims Metabolomics can qualitatively and quantitatively capture real-time dynamic changes in a wide range of small molecule metabolites. This pilot study evaluated metabolomics biomarkers and altered metabolic pathways in preschool children with AD, aiming to explore the underlying molecular mechanisms and signalling pathways of the disease. Methods Blood samples of 23 preschool children with AD and 23 healthy children without AD or any other skin disease were collected. The untargeted metabolomic measurements were performed on a SCIEX-AD ultraperformance liquid chromatography system coupled with an AB SCIEX X500B QTOF system. Characteristics of small molecules in AD children were assessed and their associations with AD clinical index were evaluated. Altered metabolic pathways in AD children were also analysed using a comprehensive metabolomics platform. Results A total of 1,969 metabolites were identified, of which AD children exhibited 377 significantly altered metabolites. Multivariate statistical analysis demonstrated that the AD group and the control group could be clearly separated. Volcano plot analysis illustrated that 144 metabolites were up-regulated and 233 metabolites were down-regulated in AD children. The Severity Scoring of Atopic Dermatitis (SCORAD index) showed a moderate-to-strong association with estrogens, carotenes, leukotrienes, flavonols and keto acids in AD children (|r|=0.440-0.557). Several pathways, including the phenylalanine metabolism, were identified as altered in AD children. Limitations A small group of children was included in the study; the results need to be validated in larger sample sizes. Conclusion Results of this study illustrate potential alterations in metabolites and the phenylalanine metabolic pathway in preschool children with AD. Although this is a pilot study with a limited sample size, it may provide a new perspective for exploring the pathogenesis of AD, and for personalised treatment modalities.