Metabolic and lipid alterations in multiple sclerosis linked to disease severity

Background: The circulating metabolome incorporates multiple levels of biological interactions and is an emerging field for biomarker discovery. However, few studies have linked metabolite levels with quantitative neurologic function assessments in people with multiple sclerosis (pwMS).Objectives: We quantified metabolomic differences between pwMS and healthy controls (HCs) and assessed the association of metabolites with disease severity.Methods: We profiled 517 metabolites using liquid chromatography-mass spectrometry (Biocrates Inc.) for participants from the MS Partners Advancing Technology and Health Solutions (MS PATHS). We conducted a multicenter cross-sectional study and applied linear regression to assess the association between metabolites and neurological function measures in multiple sclerosis (MS), including walking speed, manual dexterity, and processing speed.Results: Among 1010 participants (837 MS; 71.2% relapsing-remitting MS; 173 HC; mean age: 44.5 (standard deviation (SD): 11.4); 73.9% female; 12.7% non-white), pwMS showed decreased levels of phosphatidylcholines (PCs) and different amino acids (AAs) but increased triglycerides (TGs). Metabolites showed an association with worse neurologic function; for instance, a 1-SD decrease in PC aa C36:6 was associated with 21.36% (95% confidence interval (CI): 11.07-30.46; p = 1.35E-04) slower walking speed.Conclusions: This large study identified lipid alterations linked to MS severity. Future longitudinal studies will evaluate if these metabolite levels predict MS outcomes.