An emerging potential of metabolomics in multiple sclerosis: a comprehensive overview

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the nervous system that primarily affects young adults. Although the exact etiology of the disease remains obscure, it is clear that alterations in the metabolome contribute to this process. As such, defining a reliable and disease-specific metabolome has tremendous potential as a diagnostic and therapeutic strategy for MS. Here, we provide an overview of studies aimed at identifying the role of metabolomics in MS. These offer new insights into disease pathophysiology and the contributions of metabolic pathways to this process, identify unique markers indicative of treatment responses, and demonstrate the therapeutic effects of drug-like metabolites in cellular and animal models of MS. By and large, the commonly perturbed pathways in MS and its preclinical model include lipid metabolism involving alpha-linoleic acid pathway, nucleotide metabolism, amino acid metabolism, tricarboxylic acid cycle, D-ornithine and D-arginine pathways with collective role in signaling and energy supply. The metabolomics studies suggest that metabolic profiling of MS patient samples may uncover biomarkers that will advance our understanding of disease pathogenesis and progression, reduce delays and mistakes in diagnosis, monitor the course of disease, and detect better drug targets, all of which will improve early therapeutic interventions and improve evaluation of response to these treatments.

Keywords: Biological matrices; Biomarkers; Diagnosis; EAE; MS; Metabolites; Therapeutics.

Fig. 1

Schematic showing general workflow for a classic metabolomics study. It includes several steps, such as experimental design, sample preparation and storage, profiling, data analysis, validation, and interpretation (Created with BioRender.com (2020); https://app.biorender.com)

Fig. 2

Basic applications of metabolomics that contribute to multiple aspects of understanding, detecting, and treating multiple sclerosis

Fig. 3

KEGG-based map of altered metabolites and associated pathways derived from the major metabolomics studies in MS patients and EAE