Dietary Conjugated Linoleic Acid Supplementation Modulates CNS Autoimmunity

Objective: To characterize the immune-modulatory effects of dietary supplementation with conjugated linoleic acid (CLA) in mice and humans in the context of multiple sclerosis (MS). Background: In the recent years, an increased attention has been paid on the impact of environmental factors on MS disease susceptibility and disease activity. Especially nutritional factors are known as potent modulators of the gut-brain-axis, which is known to crucially affect onset and course of central nervous system (CNS) autoimmunity. Previous investigations revealed a clear impact of the fatty acid CLA in the modulation of autoimmunity. Design/Methods: The impact of dietary CLA supplementation was investigated in a spontaneous mouse model of CNS autoimmunity, where mice harbor myelin oligodendrocyte glycoprotein-specific T cells and B cells. In vitro and ex vivo experiments were performed to assess mechanistic effects of CLA on immune cell activity and metabolism. Furthermore, a human pilot study in 15 MS patients was performed over a period of 6 months and immunological alterations as well as gut microbiome changes were analyzed. Results: Mice receiving dietary CLA supplementation showed a significantly ameliorated disease severity and a profound reduction in CNS inflammation. This was subsequently accompanied by rebalancing systemic pro-inflammatory and regulatory immune responses, which was connected to a modification of the T cell metabolism. Besides direct effects on immune cells, CLA rich diet evoked an alteration of gut microbiota composition, which is known as important modulator of the gut-brain axis. Concurrently, the immune-modulatory and microbiota-changing effects are also determined in MS patients with continuous CLA supplementation. Conclusions: Our data illustrate the therapeutic potential of dietary supplementation with CLA as novel complementary strategy to improve CNS autoimmunity via the gut-brain-axis in mice and humans. Disclosure: Dr. Fleck has nothing to disclose. Dr. Hucke has nothing to disclose. Dr. Hartwig has nothing to disclose. Dr. Teipel has nothing to disclose. Dr. Herold has nothing to disclose. Dr. Berer has nothing to disclose. Dr. Liebmann has nothing to disclose. Dr. Kuzmanov has nothing to disclose. Dr. Grutzke has nothing to disclose. Dr. Sagredos has nothing to disclose. Dr. Eveslage has nothing to disclose. Dr. Gros has nothing to disclose. Dr. Krishnamoorthy has nothing to disclose. Dr. Dobrindt has nothing to disclose. Dr. Kuhlmann has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Wiendl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Actelion, Alexion, Biogen, Cognomed, Evgen, F. Hoffmann-La Roche Ltd, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA. Dr. Wiendl has received research support from Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme. Dr. Klotz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with received compensation for serving on Scientific Advisory Boards for Genzyme and Novartis; received speaker honoraria and travel support from Novartis, Merck Sorono, and Genzyme and Biogen; and receives research support from Novartis and Biogen. Dr. Klotz has received research support from received compensation for serving on Scientific Advisory Boards for Genzyme and Novartis; received speaker honoraria and travel support from Novartis, Merck Sorono, and Genzyme and Biogen; and receives research support from Novartis and Biogen.