The Effect of the orally applied short chain fatty acid propionate on the immune regulation in MS: results of a human proof-of-concept study (P3.388)

Objective: To investigate the effect of orally-administered propionate (PA) on Treg levels and function in healthy individuals (HC) and MS patients. Background: Dietary factors and the gut bacteria are critically involved in the etiology of complex autoimmune disorders such as MS. In a recent experimental study, we showed that short chain fatty acids (SCFA) such as PA promote regulatory Tcell (Treg) differentiation, as opposed to long chain fatty acids (LCFA) that increase Th17 differentiation in the gut. Design/Methods: In a translational proof-of-concept study approved by the ethics committee of the Ruhr-University to validate our previous experimental findings, either HC (n=30) or MS (n=80) were administered 2×500mg PA capsules daily for 14–90 days. We performed both deep immunophenotyping before and at various time points after PA intake as well as additional functional ex vivo analyses. Results: PA was well tolerated, with all volunteers reporting no noticeable side effects. We observed a significant increase of Treg (>30%) in MS patients and HC, and a concurrent significant decrease in Th17 levels after 14d of PA as compared to pre-supplementation, which was more apparent in MS patients under various approved DMTs. Moreover, our ex vivo data show a significant increase in the suppressive capability of the Treg under PA in both groups, suggesting that increased Treg differentiation is accompanied by increased their immune modulatory activity. Data supporting possible metabolomic/microbiomic changes in the fecal samples are warranted. Conclusions: Our results well translate our previous observation from an animal model to human MS, and confirm the impact of dietary fatty acids on human systemic immune response. Thus, our study suggests that PA may serve as a possible immune-supplementary agent to be administered as add-on to current first-line MS drugs. Disclosure: Dr. Duscha has nothing to disclose. Dr. Joerg has nothing to disclose. Dr. Berg has nothing to disclose. Dr. Linker has received personal compensation for activities with Bayer, Biogen, Genzyme, MerckSerono,Novartis Pharma Roche Pharma, and TEVA Pharma. Dr. Gold has received personal compensation for activities with Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience as a speaker. Dr. Gold has received personal compensation in an editorial capacity for Sage. Dr. Gold has received research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience. Dr. Haghikia has received personal compensation for activities with Biogen Idec and Bayer Healthcare as a speaker. Dr. Haghikia has received research support from Genzyme Corporation.