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Updated: May 7, 2026
The MPLEx Protocol for Multi-omic Analyses of Soil Samples
Published on: May 30, 2018
Metabolomics of Multiple Sclerosis Lesions Demonstrates Lipid Changes Linked to Alterations in Transcriptomics-Based
Dimitrios C Ladakis1, Edoardo Pedrini1, Maria I Reyes-Mantilla1
1From the Department of Neurology (D.C.L., M.I.R.-M., M.S., M.D.S., K.C.F., C.A.P., D.S.R., M.A., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Translational Neuropathology Unit (E.P., M.A.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy and Translational Neuroradiology Section (D.S.R., M.A.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
Background And Objectives:
People with multiple sclerosis (MS) have a dysregulated circulating metabolome, but the metabolome of MS brain lesions has not been studied. The aims of this study were to identify differences in the brain tissue metabolome in MS compared with controls and to assess its association with the cellular profile of corresponding tissue.
Methods:
MS tissues included samples from the edge and core of chronic active or inactive lesions and periplaque white matter (WM). Control specimens were obtained from normal WM. Metabolomic analysis was performed using mass-spectrometry coupled with liquid/gas chromatography and subsequently integrated with single-nucleus RNA-sequencing data by correlating metabolite abundances with relative cell counts, as well as individual genes using Multiomics Factor Analysis (MOFA).
Results:
Seventeen samples from 5 people with secondary progressive MS and 8 samples from 6 controls underwent metabolomic profiling identifying 783 metabolites. MS lesions had higher levels of sphingosines (false discovery rate-adjusted p-value[q] = 2.88E-05) and sphingomyelins and ceramides (q = 2.15E-07), but lower nucleotide (q = 0.05), energy (q = 0.001), lysophospholipid (q = 1.86E-07), and monoacylglycerol (q = 0.04) metabolite levels compared with control WM. Periplaque WM had elevated sphingomyelins and ceramides (q = 0.05) and decreased energy metabolites (q = 0.01) and lysophospholipids (q = 0.05) compared with control WM. Sphingolipids and membrane lipid metabolites were positively correlated with astrocyte and immune cell abundances and negatively correlated with oligodendrocytes. On the other hand, long-chain fatty acid, endocannabinoid, and monoacylglycerol pathways were negatively correlated with astrocyte and immune cell populations and positively correlated with oligodendrocytes. MOFA demonstrated associations between differentially expressed metabolites and genes involved in myelination and lipid biosynthesis.
Discussion:
MS lesions and perilesional WM demonstrated a significantly altered metabolome compared with control WM. Many of the altered metabolites were associated with altered cellular composition and gene expression, indicating an important role of lipid metabolism in chronic neuroinflammation in MS.
