Short-chain fatty acids in multiple sclerosis: Associated with disability, number of T2 lesions, and inflammatory profile

Abstract

Objective An alteration in the composition of the intestinal microbiota has been observed in patients with multiple sclerosis (pwMS) with respect to healthy controls (HC). Microorganism-derived metabolites such as short-chain fatty acids (SCFA) have been suggested to play a role in the disease. Thus, to analyze the association of SCFA with clinical and radiological parameters of the disease and with those related to the inflammatory response of the immune system. Methods Multicentric observational retrospective cross-sectional study. In addition 161 pwMS and 130 HC were included. The following plasma SCFA were analyzed using liquid chromatography coupled to mass spectrometry: acetate (AA), propionate (PA) and butyrate (BA). Blood cell subpopulations and cytokine expression were analyzed by flow cytometry. Results Plasma PA and PA/AA ratio was lower in pwMS than in HC (P = 0.0001, and P = 0.00005, respectively). PA/AA and BA/AA ratios were lower in pwMS with higher disability (P = 0.001, and P = 0.001, respectively). T2 lesion load inversely correlated with PA/AA (r = −0.353; P = 0.002) and BA/AA (r = −0.322; P = 0.005) ratios. Plasma PA/AA and/or BA/AA ratios negatively correlated with the following pro-inflammatory cytokines producing cells: GM-CSF+CD4+T, GM-CSF+CD8+T, TNF-alpha+CD4+T, TNF-alpha+CD8+T, IFN-gamma+CD4+T, IFN-gamma+CD8+T, and TNF-alpha+B cells. Interpretation In MS, plasma PA/AA and BA/AA ratios are unbalanced, promoting an environment that could be boosting the mechanisms underlying the pathogenesis of the disease. Since we have found statistical significant associations with the EDSS and the number of T2 lesions, but not with the number of relapses or gadolinium enhancing lesions, PA/AA and BA/AA ratios could be more associated with those mechanisms of the disease related to the neurodegenerative processes than those related with the activity of the disease.