Alterations in circulating fatty acid are associated with gut microbiota dysbiosis and inflammation in multiple sclerosis

A number of factors are associated with the pathogenesis of multiple sclerosis (MS), including inflammation, immune activation and alteration of gut microbiota (dysbiosis). In an attempt to rationally integrate these different factors, we performed in-depth analyses of MS-associated gut microbiota alterations and the consequences of such alterations. We observed that MS-associated dysbiosis results in a reduction of the serum concentation of short-chain fatty acid (SCFA) and an increase of medium-chain fatty acid (MCFA). SCFA support differentiation of T lymphocytes into Treg and maintain the integrity of the intestinal barrier. Further analyses confirmed that the intestinal barrier is altered and Treg lymphocytes are reduced concomitantly with the reduction of SCFA in MS. The hypothesis we put forward is that MS-associated dysbiosis results in SCFA/MCFA ratio alterations, and this is the basis of the inflammatory milieu that characterizes and accompanies MS. If this assumption is correct, then therapeutic/dietary interventions aimed at restoring a physiological (i.e., eubiotic) gut microbial ecosystem should be considered in MS therapy. Notably, serum SCFA and MCFA quantification could be a simple biomarker to evaluate the degree of inflammation in MS and in other inflammatory diseases, and to measure the efficacy of therapeutic and rehabilitation procedures in this disease.