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.

New Insights into Multiple Sclerosis Mechanisms: Lipids on the Track to Control Inflammation and Neurodegeneration

“…Lipid metabolites are currently believed to be useful biomarkers because of their dynamic profile changes in various conditions. The lipidomic approach may be beneficial in examining the effects of therapeutical interventions and has been suggested for use in monitoring in clinical therapeutic trials [ 10 ]. A few recently published studies explored this approach with regard to MS patients treated with DMT.…”

“…Lipids are not only substantially involved in the formation of myelin sheath (and thus could be a hallmark of demyelination and repair), but are also engaged in the cell signaling, in communication, and in transport in the CNS [ 8 ]. Thus, they seem likely candidates for biomarkers of processes underlying active and progressive phase of MS, as well as potential target for new, effective, and stage-specific therapeutic interventions [ 9 , 10 ].…”

Blood-based untargeted metabolomics in Relapsing-Remitting Multiple Sclerosis revealed the testable therapeutic target

“…The art of metabolomics can be implicated to differentiate between a diseased vs. a nondiseased state; therefore, it has gained significant translational importance in MS studies for the possible development of MS associated surrogate biomarkers and to monitor the disease progression with or without a therapeutic intervention. A few studies have employed the untargeted metabolomics approach to identify MS patients' cardinal metabolic changes (Zahoor et al, 2021). However, most of the studies used a single platform with the ability to identify limited metabolites (Zahoor et al, 2021).…”

A Deep Transcriptome Meta-Analysis Reveals Sex-based Molecular Differences in Multiple Sclerosis

“…The biological process we have found is rather generic, as it is related to the secretion of signals into the extracellular medium from a cellular source, but without further details about the signal or the origin of the secretion. For the KEGG pathway, previous studies have shown the role of pathways associated with these amino acids in the modulation of the autoimmune response, as well as mechanisms of cytotoxicity and neuroprotection [61, 62]. However, these studies did not take into account sex as factor and did not detect its influence on these alterations.…”