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


Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
19 03 2020
Historique:
received: 09 11 2018
revised: 27 10 2019
accepted: 13 02 2020
pubmed: 12 3 2020
medline: 21 10 2020
entrez: 12 3 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32160527
pii: S0092-8674(20)30212-9
doi: 10.1016/j.cell.2020.02.035
pii:
doi:

Substances chimiques

Propionates 0
propionic acid JHU490RVYR

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1067-1080.e16

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests R.G. and A.H. have filed a patent on the supportive immunomodulatory effect of C3-C8 aliphatic fatty acids.

Auteurs

Alexander Duscha (A)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Barbara Gisevius (B)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Sarah Hirschberg (S)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Nissan Yissachar (N)

The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Gabriele I Stangl (GI)

Institute of Agricultural and Nutritional Sciences, Martin Luther University, Halle-Wittenberg 06108, Germany.

Eva Dawin (E)

Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum 44801, Germany; Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund 44139, Germany.

Verian Bader (V)

Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum 44801, Germany.

Stefanie Haase (S)

Department of Neurology, University of Regensburg, Regensburg 93053, Germany.

Johannes Kaisler (J)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Christina David (C)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Ruth Schneider (R)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Riccardo Troisi (R)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Daniel Zent (D)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Tobias Hegelmaier (T)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Nikolaos Dokalis (N)

Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany.

Sara Gerstein (S)

The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Sara Del Mare-Roumani (S)

The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Sivan Amidror (S)

The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel; Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Ori Staszewski (O)

Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany; Berta Ottenstein Program for Advanced Clinician Scientists, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany.

Gereon Poschmann (G)

Molecular Proteomics Laboratory (MPL), Bio-Medical Research Center (BMFZ), Heinrich Heine University, Düsseldorf 40225, Germany; Institute for Molecular Medicine, University Hospital Düsseldorf, Düsseldorf 40225, Germany.

Kai Stühler (K)

Molecular Proteomics Laboratory (MPL), Bio-Medical Research Center (BMFZ), Heinrich Heine University, Düsseldorf 40225, Germany; Institute for Molecular Medicine, University Hospital Düsseldorf, Düsseldorf 40225, Germany.

Frank Hirche (F)

Institute of Agricultural and Nutritional Sciences, Martin Luther University, Halle-Wittenberg 06108, Germany.

Andras Balogh (A)

Experimental and Clinical Research Center, a Joint Cooperation of the Max Delbruck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin 13125, Germany.

Stefan Kempa (S)

Integrative Metabolomics and Proteomics, Berlin Institute of Medical Systems Biology/Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.

Pascal Träger (P)

Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University (FAU) Erlangen-Nürnberg, Erlangen 91054, Germany.

Mario M Zaiss (MM)

Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University (FAU) Erlangen-Nürnberg, Erlangen 91054, Germany.

Jacob Bak Holm (JB)

Clinical Microbiomics A/S, Copenhagen 2200, Denmark.

Megan G Massa (MG)

Department of Integrative Biology and Physiology, Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Henrik Bjørn Nielsen (HB)

Clinical Microbiomics A/S, Copenhagen 2200, Denmark.

Andreas Faissner (A)

Department of Cell Morphology and Molecular Neurobiology, Ruhr University Bochum, Bochum 44801, Germany.

Carsten Lukas (C)

Department of Radiology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Sören G Gatermann (SG)

Department of Medical Microbiology, Ruhr University Bochum, Bochum 44801, Germany.

Markus Scholz (M)

Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig 04109, Germany.

Horst Przuntek (H)

Clinic of Neurology II, EVK Hattingen, Hattingen 45525, Germany.

Marco Prinz (M)

Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany; Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany.

Sofia K Forslund (SK)

Experimental and Clinical Research Center, a Joint Cooperation of the Max Delbruck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin 13125, Germany; Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany.

Konstanze F Winklhofer (KF)

Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum 44801, Germany.

Dominik N Müller (DN)

Experimental and Clinical Research Center, a Joint Cooperation of the Max Delbruck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin 13125, Germany; Max Delbruck Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany.

Ralf A Linker (RA)

Department of Neurology, University of Regensburg, Regensburg 93053, Germany.

Ralf Gold (R)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.

Aiden Haghikia (A)

Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany. Electronic address: aiden.haghikia@rub.de.

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