Role of Fatty Acids in Multipe Sclerosis: Therapeutic Potential of Propionic Acid (P1.374)

Abstract

Objective: To investigate the impact of oral propionate (PA) - a short chain fatty acid (SCFA) - on regualatory T cells (Treg) in healthy volunteers and multiple sclerosis (MS) patients in vivo. Background: In the in the small intestine, we have recently shown that depending on their chain length fatty acids (FA) either induce an in increase Th17 (long chain FA) or Treg differentiation (SCFA). Furthermore, we could show that while long chain FA have a detrimental effect on the course of experimental autoimmune encephalomyelitis (EAE), a model of MS, SCFA ameliorate EAE mainly by promoting the differentiation of Treg. Methods: In a proof of concept study (approved by the local ethics committee), we transferred our observations on PA to healthy individuals and MS patients by orally administrating PA (1g daily) - an approved food additive with no safety concerns - in capsules for 14-60 days. The study included washout intervals after 14-60 days. A detailed flow cytometry immunophenotypic assessment of T cell subsets before and at several time points after PA intake was performed, as well as additional functional correlates, such as in vitro suppression assays. Results: We report the first beneficial in vivo effects of PA in humans. PA intake was well tolerated by all volunteers and no side effects occurred. Treg frequencies in all treated individuals increased (up to 25-30[percnt]), which was accompanied by a significant decrease of Th17 cells. Increased Treg frequencies were maintained for 2-3 weeks after withdrawal of PA, and similar to baseline frequencies after 2 months of washout. Conclusions: Our results underline the influence of nutritive FA on systemic immune response und may be included in an add-on regimen of PA in addition to established first line MS drugs.

Disclosure: Dr. Haghikia has nothing to disclose. Dr. Duscha has nothing to disclose. Dr. Berg has nothing to disclose. Dr. Jörg has nothing to disclose. Dr. Wilck has nothing to disclose. Dr. Müller has nothing to disclose. Dr. Linker has nothing to disclose. Dr. Gold has received research support from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience.