Propionic acid modulates T effector cell balance and function in MS patients
ECTRIMS Online Library. Duscha A. 10/25/17; 202422; 72
Alexander Duscha
Alexander Duscha
Contributions
Abstract

Abstract: 72

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - 17 Environmental factors

Background: Latest advances in research focusing on environmental factors as risk factors in multiple sclerosis (MS) point to the important role of diet and the gut in the context of its microbiotic and metabolic composition. In the animal model MOG-induced experimental autoimmune encephalomyelitis (EAE) fatty acids as microbial byproducts modulate the gut-associated immune system. We showed that short chain fatty acids like propionate (PA) increased regulatory T cell (Treg) differentiation in vitro and ameliorated the course of EAE. Furthermore, we demonstrated that microbiome composition during EAE was altered by long chain fatty acid-enriched diet which led to a shift in relative abundance of bacterial phyla.
Objective:
To investigate effects of orally applied PA on immune cell phenotype and function as well as individual microbiome composition and diversity of MS patients and healthy controls (HC).
Methods:
This translational proof of concept-study was performed after approval by the ethic committee of the Ruhr-University Bochum, with a cohort of 90 MS patients (under diverse disease modifying treatment) and 30 HC. PA was administered at 500mg twice daily for 14 to up to 90 days. PA has been approved as food additive without safety concerns by European and American Food Safety Agencies.
Results: PA was well tolerated with no reported side effects. Immune phenotyping displayed a significant reduction in pro-inflammatory T helper 17 cells after 14 days of PA intake, more prominent in MS patients. Concomitantly, Treg levels were increased up to 30% from initial base level. Additionally, we observed a significant increase in Treg modulatory capacities during PA treatment in MS patients in which Treg function has been shown to be decreased. We validated significant differences in the microbiome of MS patients versus HC. Furthermore, Shannon Alpha Diversity as well as Principal Coordinate Analysis displayed a significant reduction in microbiome diversity of relapsing-remitting MS (RRMS) patients and a separate clustering of RRMS patients' microbiome.
Conclusion:
By this study, we translate our initial findings from EAE to MS. Furthermore, we verify the influence of dietary fatty acids on the systemic immune response in humans as well as the importance of the microbiome in association with neurological disease. Hence, our findings suggest PA as a possible immuno-modulatory supplement for application as add-on treatment to currently approved first line MS drugs.
Disclosure: Alexander Duscha: nothing to disclose
Stefanie Jörg: nothing to disclose
Johannes Berg: nothing to disclose
Jacob Bak Holm: nothing to disclose
Ralf A. Linker: received travel support and/or compensation for activities with Allmirall, Bayer Healthcare, Biogen, Fresenius, Genzyme, Merck, Novartis, Roche and TEVA as well as research support from Biogen, Merck and Novartis.
Ralf Gold: 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: received limited travel grants from Bayer Healthcare and Genzyme, and limited research grants from Genzyme.



Abstract: 72

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - 17 Environmental factors

Background: Latest advances in research focusing on environmental factors as risk factors in multiple sclerosis (MS) point to the important role of diet and the gut in the context of its microbiotic and metabolic composition. In the animal model MOG-induced experimental autoimmune encephalomyelitis (EAE) fatty acids as microbial byproducts modulate the gut-associated immune system. We showed that short chain fatty acids like propionate (PA) increased regulatory T cell (Treg) differentiation in vitro and ameliorated the course of EAE. Furthermore, we demonstrated that microbiome composition during EAE was altered by long chain fatty acid-enriched diet which led to a shift in relative abundance of bacterial phyla.
Objective:
To investigate effects of orally applied PA on immune cell phenotype and function as well as individual microbiome composition and diversity of MS patients and healthy controls (HC).
Methods:
This translational proof of concept-study was performed after approval by the ethic committee of the Ruhr-University Bochum, with a cohort of 90 MS patients (under diverse disease modifying treatment) and 30 HC. PA was administered at 500mg twice daily for 14 to up to 90 days. PA has been approved as food additive without safety concerns by European and American Food Safety Agencies.
Results: PA was well tolerated with no reported side effects. Immune phenotyping displayed a significant reduction in pro-inflammatory T helper 17 cells after 14 days of PA intake, more prominent in MS patients. Concomitantly, Treg levels were increased up to 30% from initial base level. Additionally, we observed a significant increase in Treg modulatory capacities during PA treatment in MS patients in which Treg function has been shown to be decreased. We validated significant differences in the microbiome of MS patients versus HC. Furthermore, Shannon Alpha Diversity as well as Principal Coordinate Analysis displayed a significant reduction in microbiome diversity of relapsing-remitting MS (RRMS) patients and a separate clustering of RRMS patients' microbiome.
Conclusion:
By this study, we translate our initial findings from EAE to MS. Furthermore, we verify the influence of dietary fatty acids on the systemic immune response in humans as well as the importance of the microbiome in association with neurological disease. Hence, our findings suggest PA as a possible immuno-modulatory supplement for application as add-on treatment to currently approved first line MS drugs.
Disclosure: Alexander Duscha: nothing to disclose
Stefanie Jörg: nothing to disclose
Johannes Berg: nothing to disclose
Jacob Bak Holm: nothing to disclose
Ralf A. Linker: received travel support and/or compensation for activities with Allmirall, Bayer Healthcare, Biogen, Fresenius, Genzyme, Merck, Novartis, Roche and TEVA as well as research support from Biogen, Merck and Novartis.
Ralf Gold: 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: received limited travel grants from Bayer Healthcare and Genzyme, and limited research grants from Genzyme.



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