Short-chain fatty acids and intestinal inflammation in multiple sclerosis: modulation of female susceptibility by microbial products?

Abstract

Background: Multiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system. Experi mental 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 benefcial efects (mediated by immunomodulatory mecha nisms) after oral administration of the SCFA propionate in MS patients. Based on available evidence, we investigated whether SCFAs and the fecal infammation marker calprotectin are altered in MS. Methods: 76 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 com pared between MS patients and controls, and were analyzed for an association with demographic as well as clinical parameters. Results: Median fecal calprotectin concentrations were within normal range in both groups without any group-spe cifc diferences. Fecal SCFA concentrations showed a non-signifcant reduction in MS patients compared to healthy subjects. Female subjects showed signifcantly reduced SCFA concentrations compared to male subjects. Conclusions: In our cohort of MS patients, we found no evidence of an active intestinal infammation. Yet, the vast majority of the investigated MS patients was under immunotherapy which might have afected the outcome meas ures. The sex-associated diference 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 efects and those caused by the therapeutic regime.