Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism

Item Type:	Article
Title:	Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism
Creators Name:	Duscha, A. and Gisevius, B. and Hirschberg, S. and Yissachar, N. and Stangl, G.I. and Eilers, E. and Bader, V. and Haase, S. and Kaisler, J. and David, C. and Schneider, R. and Troisi, R. and Zent, D. and Hegelmaier, T. and Dokalis, N. and Gerstein, S. and Del Mare-Roumani, S. and Amidror, S. and Staszewski, O. and Poschmann, G. and Stühler, K. and Hirche, F. and Balogh, A. and Kempa, S. and Träger, P. and Zaiss, M.M. and Holm, J.B. and Massa, M.G. and Nielsen, H.B. and Faissner, A. and Lukas, C. and Gatermann, S.G. and Scholz, M. and Przuntek, H. and Prinz, M. and Forslund, S.K. and Winklhofer, K.F. and Müller, D.N. and Linker, R.A. and Gold, R. and Haghikia, A.
Abstract:	Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly reduced PA amounts compared with controls, particularly after the first relapse. In a proof-of-concept study, we supplemented PA to therapy-naive MS patients and as an add-on to MS immunotherapy. After 2 weeks of PA intake, we observed a significant and sustained increase of functionally competent regulatory T (Treg) cells, whereas Th1 and Th17 cells decreased significantly. Post-hoc analyses revealed a reduced annual relapse rate, disability stabilization, and reduced brain atrophy after 3 years of PA intake. Functional microbiome analysis revealed increased expression of Treg-cell-inducing genes in the intestine after PA intake. Furthermore, PA normalized Treg cell mitochondrial function and morphology in MS. Our findings suggest that PA can serve as a potent immunomodulatory supplement to MS drugs.
Keywords:	Autoimmune Diseases, Multiple Sclerosis, Propionic Acid, Immune Modulation, Regulatory T Cells, Microbiome, Neuroregeneration
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	180
Number:	6
Page Range:	1067-1080
Date:	19 March 2020
Official Publication:	https://doi.org/10.1016/j.cell.2020.02.035
PubMed:	View item in PubMed

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