Recent Advances in Metabolomics and Lipidomics Studies in Human and Animal Models of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease of the central nervous system (CNS) that leads to a loss of myelin. There are three main types of MS: relapsing-remitting MS (RRMS) and primary and secondary progressive disease (PPMS, SPMS). The differentiation in the pathogenesis of these two latter courses is still unclear. The underlying mechanisms of MS are yet to be elucidated, and the treatment relies on immune-modifying agents. Recently, lipidomics and metabolomics studies using human biofluids, mainly plasma and cerebrospinal fluid (CSF), have suggested an important role of lipids and metabolites in the pathophysiology of MS. In this review, the results from studies on metabolomics and lipidomics analyses performed on biological samples of MS patients and MS-like animal models are presented and analyzed. Based on the collected findings, the biochemical pathways in human and animal cohorts involved were investigated and biological mechanisms and the potential role they have in MS are discussed. Limitations and challenges of metabolomics and lipidomics approaches are presented while concluding that metabolomics and lipidomics may provide a more holistic approach and provide biomarkers for early diagnosis of MS disease.

Keywords: GC-MS; LC-MS; NMR; biomarkers; lipidomics; meta-analysis; metabolomics; multiple sclerosis; pathway analysis; review.

Figure 1

Metabolic pathway analysis in biological samples (brain, CSF, plasma, serum, urine, tears) of 31 human (RRMS, CIS, PPMS, SPMS) studies. The size of the circle corresponds to the pathway impact score (x-axis). Darker circle colors indicate more significant changes (y-axis) in metabolites in the corresponding pathway. Significant metabolic pathways (p < 0.05) are numbered in decreasing order (i.e., pathway 1 being most significant to pathway 16 being least significant).

Figure 2

Dysregulated metabolic pathways in human samples, comparing different MS disease forms with healthy controls. (A) Intersection analysis of metabolic pathways dysregulated among progressive MS (PPMS, SPMS) and RRMS group human plasma samples. On the left are the significantly altered pathways in progressive MS vs. controls, on the right are all the significantly altered pathways in RRMS vs. controls, and the middle intersection is the common pathway (glycerophospholipid metabolism) among progressive and RMMS vs. control human plasma samples. (B) Intersection analysis of metabolic pathways among progressive MS (PPMS, SPMS) and RRMS group human CSF samples. On the left are all the altered pathways in progressive vs. control CSF samples, on the right are all the altered pathways in RRMS vs. control CSF samples, and the middle intersection is the common pathway (sphingolipid metabolism) among progressive and RMMS vs. control human CSF samples. (C) Intersection analysis of metabolic pathways among human plasma and CSF samples. On the left are all the altered pathways in combined progressive and RRMS vs. control plasma samples, on the right are all the altered pathways in combined progressive and RRMS vs. control CSF samples, and the middle intersection is the altered pathway in common (tryptophan metabolism) among human plasma and CSF samples.

Figure 3

Metabolic pathway analysis in biological samples (brain and plasma) of 6 mouse models of CNS demyelination studies. The size of the circle corresponds to the pathway impact score (x-axis). Darker circle colors indicate more significant changes (y-axis) in metabolites in the corresponding pathway. Significant metabolic pathways (p < 0.05) are numbered in decreasing order (i.e., pathway 1 being most significant to pathway 6 being least significant).