Abstract
Introduction and objectives
Multiple sclerosis (MS) is a disease of the central nervous system associated with immune dysfunction, demyelination, and neurodegeneration. The disease has heterogeneous clinical phenotypes such as relapsing–remitting MS (RRMS) and progressive multiple sclerosis (PMS), each with unique pathogenesis. Metabolomics research has shown promise in understanding the etiologies of MS disease. However, there is a paucity of clinical studies with follow-up metabolomics analyses. This 5-year follow-up (5YFU) cohort study aimed to investigate the metabolomics alterations over time between different courses of MS patients and healthy controls and provide insights into metabolic and physiological mechanisms of MS disease progression.
Methods
A cohort containing 108 MS patients (37 PMS and 71 RRMS) and 42 controls were followed up for a median of 5 years. Liquid chromatography–mass spectrometry (LC–MS) was applied for untargeted metabolomics profiling of serum samples of the cohort at both baseline and 5YFU. Univariate analyses with mixed-effect ANCOVA models, clustering, and pathway enrichment analyses were performed to identify patterns of metabolites and pathway changes across the time effects and patient groups.
Results and conclusions
Out of 592 identified metabolites, the PMS group exhibited the most changes, with 219 (37%) metabolites changed over time and 132 (22%) changed within the RRMS group (Bonferroni adjusted P < 0.05). Compared to the baseline, there were more significant metabolite differences detected between PMS and RRMS classes at 5YFU. Pathway enrichment analysis detected seven pathways perturbed significantly during 5YFU in MS groups compared to controls. PMS showed more pathway changes compared to the RRMS group.
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Data Availability
The statistical findings of this research are available on request to the study principal investigator (RZ) and statistician (RHB) upon approval by the appropriate Institutional Review Board of both parties.
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Acknowledgements
MR, RB and RHB received funding from Department of Defense Congressionally Directed Medical Research Programs (MS190096), USAMRDC, Multiple Sclerosis Research Program is gratefully acknowledged. The funder had no role in the design of the study or the data analysis.
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TS, RB, MR, RHB - prepared the manuscript; TS, RHB - prepared Figures and Tables; All authors reviewed the manuscript.
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Shi, T., Browne, R.W., Tamaño-Blanco, M. et al. Metabolomic profiles in relapsing–remitting and progressive multiple sclerosis compared to healthy controls: a five-year follow-up study. Metabolomics 19, 44 (2023). https://doi.org/10.1007/s11306-023-02010-0
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DOI: https://doi.org/10.1007/s11306-023-02010-0