Contributions
Abstract: P1160
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Dietary factors and the gut bacteria are increasingly being suspected to be critically involved in the etiology of autoimmune disorders such as MS. We have recently shown that, in a disease model of MS short chain fatty acids (SCFA) such as propionate (PA) promote regulatory T cell (Treg) differentiation, while long chain fatty acids (LCFA) increase Th17 differentiation in the small intestine. In vivo, PA treatment ameliorated the course of a MOG-induced experimental autoimmune encephalomyelitis (EAE). Conversely, treatment with LCFA worsened disease course by increasing Th17 differentiation.
Objective: Our study investigates the effect of orally-administered PA on Treg levels and function in healthy individuals and MS patients.
Design and methods: In a translational proof-of-concept study to validate our findings in the animal model, and after approval by the ethics committee of the Ruhr-University Bochum either healthy controls (n=30) or MS (n=60; under various DMTs) participants were administered 2x500 mg PA capsules daily for 14-90 days. Sodium-propionate (PA) is approved as a food additive with no safety concerns by European (EFSA) and the American Food Safety Agencies (FDA). We performed both deep immunophenotyping of T cell subsets before and at various time points after PA intake as well as additional functional ex vivo analyses.
Results: The PA was well tolerated, with all volunteers reporting no noticeable side effects. We observed a significant increase of Treg of about 30% in MS patients and healthy controls, and a concurrent significant decrease in Th17 (and Th1) levels already after 14d of PA as compared to pre-supplementation, which was more apparent in MS patients. Moreover, our ex vivo data show a significant increase in the suppressive capability of the Treg under PA in both groups, suggesting that not only Treg differentiation is increased but also their immune modulatory activity.
Conclusions: These initial results not only translate our previous observation from an animal model to human MS, but more importantly they 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:
Alexander Duscha: nothing to disclose
Stefanie Jörg: nothing to disclose
Johannes Berg: nothing to disclose
Ralf A. Linker: holds an endowed professorship supported by the Novartis Foundation
Ralf Gold: has received payments for consultancy from Biogen and Teva;
speaker honoraria and research grants from Biogen Idec Germany, Teva,
Sanofi Aventis, Novartis, Bayer Healthcare and Merck Serono.
Aiden Haghikia: has received limited travel grants from Bayer
Healthcare and Genzyme, and limited research grants from Genzyme.
Abstract: P1160
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: Dietary factors and the gut bacteria are increasingly being suspected to be critically involved in the etiology of autoimmune disorders such as MS. We have recently shown that, in a disease model of MS short chain fatty acids (SCFA) such as propionate (PA) promote regulatory T cell (Treg) differentiation, while long chain fatty acids (LCFA) increase Th17 differentiation in the small intestine. In vivo, PA treatment ameliorated the course of a MOG-induced experimental autoimmune encephalomyelitis (EAE). Conversely, treatment with LCFA worsened disease course by increasing Th17 differentiation.
Objective: Our study investigates the effect of orally-administered PA on Treg levels and function in healthy individuals and MS patients.
Design and methods: In a translational proof-of-concept study to validate our findings in the animal model, and after approval by the ethics committee of the Ruhr-University Bochum either healthy controls (n=30) or MS (n=60; under various DMTs) participants were administered 2x500 mg PA capsules daily for 14-90 days. Sodium-propionate (PA) is approved as a food additive with no safety concerns by European (EFSA) and the American Food Safety Agencies (FDA). We performed both deep immunophenotyping of T cell subsets before and at various time points after PA intake as well as additional functional ex vivo analyses.
Results: The PA was well tolerated, with all volunteers reporting no noticeable side effects. We observed a significant increase of Treg of about 30% in MS patients and healthy controls, and a concurrent significant decrease in Th17 (and Th1) levels already after 14d of PA as compared to pre-supplementation, which was more apparent in MS patients. Moreover, our ex vivo data show a significant increase in the suppressive capability of the Treg under PA in both groups, suggesting that not only Treg differentiation is increased but also their immune modulatory activity.
Conclusions: These initial results not only translate our previous observation from an animal model to human MS, but more importantly they 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:
Alexander Duscha: nothing to disclose
Stefanie Jörg: nothing to disclose
Johannes Berg: nothing to disclose
Ralf A. Linker: holds an endowed professorship supported by the Novartis Foundation
Ralf Gold: has received payments for consultancy from Biogen and Teva;
speaker honoraria and research grants from Biogen Idec Germany, Teva,
Sanofi Aventis, Novartis, Bayer Healthcare and Merck Serono.
Aiden Haghikia: has received limited travel grants from Bayer
Healthcare and Genzyme, and limited research grants from Genzyme.