Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism

Duscha A, Gisevius B, Hirschberg S, Yissachar N, Stangl GI, Eilers E, Bader V, Haase S, Kaisler J, David C, Schneider R, Troisi R, Zent D, Hegelmaier T, Dokalis N, Gerstein S, Del Mare-Roumani S, Amidror S, Staszewski O, Poschmann G, Stühler K, Hirche F, Balogh A, Kempa S, Träger P, Zaiss M, Holm JB, Massa MG, Nielsen HB, Faissner A, Lukas C, Gatermann SG, Scholz M, Przuntek H, Prinz M, Forslund SK, Winklhofer KF, Müller DN, Linker RA, Gold R, Haghikia A (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Cell Elsevier

Book Volume: 180

Pages Range: 1067-1080.e16

Journal Issue: 6

DOI: 10.1016/j.cell.2020.02.035

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.

Authors with CRIS profile

Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Bar-Ilan University IL Israel (IL) Katholisches Klinikum Bochum (St. Josef- und St. Elisabeth-Hospital gGmbH) DE Germany (DE) Universität Leipzig DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE) Ruhr-Universität Bochum (RUB) DE Germany (DE) Martin-Luther-Universität Halle-Wittenberg (MLU) DE Germany (DE) Universität Regensburg DE Germany (DE) Clinical Microbiomic A/S DK Denmark (DK) University of California Los Angeles (UCLA) US United States (USA) (US) Heinrich-Heine-Universität Düsseldorf DE Germany (DE)

How to cite

APA:

Duscha, A., Gisevius, B., Hirschberg, S., Yissachar, N., Stangl, G.I., Eilers, E.,... Haghikia, A. (2020). Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism. Cell, 180(6), 1067-1080.e16. https://doi.org/10.1016/j.cell.2020.02.035

MLA:

Duscha, Alexander, et al. "Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism." Cell 180.6 (2020): 1067-1080.e16.

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