¹ H-NMR analysis provides a metabolomic profile of patients with multiple sclerosis

Abstract

Objective:To investigate the metabolomic profiles of patients with multiple sclerosis (MS) and to define the metabolic pathways potentially related to MS pathogenesis.Methods:Plasma samples from 73 patients with MS (therapy-free for at least 90 days) and 88 healthy controls (HC) were analyzed by 1H-NMR spectroscopy. Data analysis was conducted with principal components analysis followed by a supervised analysis (orthogonal partial least squares discriminant analysis [OPLS-DA]). The metabolites were identified and quantified using Chenomx software, and the receiver operating characteristic (ROC) curves were calculated.Results:The model obtained with the OPLS-DA identified predictive metabolic differences between the patients with MS and HC (R2X = 0.615, R2Y = 0.619, Q2 = 0.476; p < 0.001). The differential metabolites included glucose, 5-OH-tryptophan, and tryptophan, which were lower in the MS group, and 3-OH-butyrate, acetoacetate, acetone, alanine, and choline, which were higher in the MS group. The suitability of the model was evaluated using an external set of samples. The values returned by the model were used to build the corresponding ROC curve (area under the curve of 0.98).Conclusion:NMR metabolomic analysis was able to discriminate different metabolic profiles in patients with MS compared with HC. With the exception of choline, the main metabolic changes could be connected to 2 different metabolic pathways: tryptophan metabolism and energy metabolism. Metabolomics appears to represent a promising noninvasive approach for the study of MS.

Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation

“…Metabolomics studies in rodent EAE have demonstrated changes in branched chain amino acid and histidine metabolism (20,21). Previous studies in MS patients have also noted differences in amino acid metabolism (branched-chain amino acid, alanine, arginine) (22,23) or in multiple amino acids (tryptophan, alanine, and isoleucine) in addition to energy metabolites (24). Elevations in lactate, certain fatty acids, and N-acetyl species and reductions in glucose and phosphocholine as well as differences in phospholipid metabolism have also been observed in MS (6,8).…”

Assessing the Metabolomic Profile of Multiple Sclerosis Patients Treated with Interferon Beta 1a by 1H-NMR Spectroscopy

“…Previous studies using 1 H-NMR spectroscopy have indicated that the plasma concentrations of some metabolites, particularly those involved in energy and tryptophan metabolism, are able to discriminate MS patients from healthy controls [17]. Similarly, some evidence has suggested that serum metabolite profiles can distinguish patients with different subtypes and stages of MS, potentially identifying those with a prevalent inflammatory course [16].…”

“…In particular, metabolomics with the detailed analysis of metabolites detected in a biological system reveals the signatures of dynamic multiparametric responses to different endogenous and exogenous processes, while evaluating epigenetic modifications [14,15]. To date, metabolomic research in MS has been largely focused on identification of potential biomarkers for diagnosis and disease monitoring [16][17][18], whereas little is known about the metabolomic profiles induced by DMDs and related to the therapeutic response or possible adverse effects.…”

Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis ofKrabbe disease

“…The role of each of these metabolites and correlation with disease pathogenesis remain unclear but warrant further investigation. For example, several of our findings were consistent with previous metabolomic studies in other demyelinating diseases, including multiple sclerosis (Tavazzi et al, ; Gonzalo et al, ; Mangalam et al, ; Bhargava et al, ; Pieragostino et al, ; Cocco et al, ). In particular, in a metabolomics study from the CSF of a rat model of experimental autoimmune enchephalomyelitis (EAE), BCAAs and putrescine were both found to increase with disease progression (Noga et al, ).…”