Supplementation of the short chain fatty acid, propionic acid restores regulatory T cell function in multiple sclerosis patients – a proof-of-concept study

The impact of the gut microbiome and its metabolites on human health and disease is being increasingly appreciated. Such metabolites include fatty acids (FA), an integral component of the daily Western diet. FA have long been implied in obesity and metabolic disorders, more recently also in autoimmune diseases, such as multiple sclerosis (MS). In a mouse model resembling MS, the experimental autoimmune encephalomyelitis (EAE) we recently showed the opposing effect of long chain (LCFA) and short chain (SCFA) FA, i.e. propionic acid (PA) on intestinal T cell differentiation and disease course. Here, in a translational approach, we supplemented the FDA approved food additive PA in MS patients in addition to their pre-existing immunomodulatory drugs. After 14 days of PA we observed a significant increase of Treg accompanied by an enhanced suppressive function, while Th1 and Th17, and their signature cytokines were significantly decreased. The PA-effect was long-lasting in patients who continued PA-supplementation on a voluntary basis. Moreover, we observed an distinct microbiome composition in MS patients compared to healthy controls (HC). Our findings suggest that PA could serve as a potent immunomodulatory supplement to be used as add on to current existing and approved MS drugs.