Abstract
BackgroundMultiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system. Experimental data suggest a role of intestinal microbiota and microbial products such as short-chain fatty acids (SCFAs) in the pathogenesis of MS. A recent clinical study reported beneficial effects (mediated by immunomodulatory mechanisms) after oral administration of the SCFA propionate in MS patients. Based on available evidence, we investigated whether SCFAs and the fecal inflammation marker calprotectin are altered in MS.Methods76 subjects (41 patients with relapsing–remitting MS and 35 age-matched controls) were investigated in this case–control study. All subjects underwent clinical assessment with established clinical scales and provided fecal samples for a quantitative analysis of fecal SCFA and fecal calprotectin concentrations. Fecal markers were compared between MS patients and controls, and were analyzed for an association with demographic as well as clinical parameters.ResultsMedian fecal calprotectin concentrations were within normal range in both groups without any group-specific differences. Fecal SCFA concentrations showed a non-significant reduction in MS patients compared to healthy subjects. Female subjects showed significantly reduced SCFA concentrations compared to male subjects.ConclusionsIn our cohort of MS patients, we found no evidence of an active intestinal inflammation. Yet, the vast majority of the investigated MS patients was under immunotherapy which might have affected the outcome measures. The sex-associated difference in fecal SCFA concentrations might at least partially explain female predominance in MS. Large-scale longitudinal studies including drug-naïve MS patients are required to determine the role of SCFAs in MS and to distinguish between disease-immanent effects and those caused by the therapeutic regime.
Highlights
Multiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system
EAE onset is strongly linked to microbial stimuli: colonization of germ-free mice with commensal bacteria leads to EAE development [5], while mice that are kept under germfree condition do not routinely develop EAE
Fecal short‐chain fatty acid concentrations Short-chain fatty acids (SCFA) concentrations were descriptively lower in relapsing–remitting MS (RRMS) patients compared to controls
Summary
Multiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system. Multiple Sclerosis (MS) is an auto-inflammatory disease of the central nervous system (CNS) Apart from trauma, it is the most common disease leading to Becker et al Autoimmun Highlights (2021) 12:7 regulatory T cells (Tregs) characterize the pro-inflammatory environment in MS [2, 3]. The experimental autoimmune encephalomyelitis (EAE) mouse model is the most widely used animal model for MS In this model, mice receive CD4 + lymphocytes specific for myelin or become immunized with proteins or peptides deriving from myelin. Mice receive CD4 + lymphocytes specific for myelin or become immunized with proteins or peptides deriving from myelin This intervention results in CNS inflammation and MS-typical features [4]. Other studies reported significant beneficial effects in the EAE model by the SCFAs valerate and propionate [7, 13]
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