Assessment of plasma metabolomic biomarkers in various pediatric diseases

ABSTRACT:

BACKGROUND: Metabolites that are direct read-outs of the functional status of cells, tissues, and organs can be more closely associated with phenotype compared to other omics profiles. Previous studies showed the analytical validity of metabolomic platforms and demonstrated a utility in interpreting the impact of genetic variants.

METHODS: To explore the utility of metabolomics in the context of precision medicine, we used an untargeted ultrahigh performance liquid chromatography-tandem mass spectroscopy to characterize plasma samples collected from generally healthy individuals and a deeply phenotyped cohort with various pediatric diseases.

RESULTS: A total of 1244 metabolites including 224 xenobiotic compounds were quantitatively measured for 169 individuals and thus revealed complex correlation structure within and between metabolic pathways. As proofs-of-concept, perturbations of phenylalanine and tyrosine metabolic pathways in a patient with phenylketonuria and carbohydrate metabolism in patients with diabetes mellitus were recapitulated as well as highlighting other biomarkers such as 1,5−anhydroglucitol for monitoring glycemic control. We discovered multiple metabolites that were significantly associated with different diseases using an exposome-wide association analysis framework. Amino acids showed significantly changed in patients with congenital heart diseases, and multiple lipid compounds were significant for Crohn’s disease. Notably, gut microbial products showed different concentrations with the use of antibiotics. Each xenobiotic compound showed a distinct correlation pattern with endogenous metabolites.

CONCLUSIONS: Untargeted metabolomics could be a powerful precision medicine platform in itself or in combination with WES. The impact of exogenous exposures such as microbial products, drugs and environmental toxicants can be directly estimated by monitoring internal exposome, enabling the discovery of novel diagnosis and treatment biomarkers in diverse diseases. A repository of metabolomics data is required, which will enable the comparison between different platforms and concentrations of thousands of metabolites across individuals.

INSTRUMENT(S): Q Exactive

SUBMITTER: Carles Hernandez-Ferrer 

PROVIDER: MTBLS948 | MetaboLights | 2024-05-14

REPOSITORIES: MetaboLights