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Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism.
Duscha, Alexander; Gisevius, Barbara; Hirschberg, Sarah; Yissachar, Nissan; Stangl, Gabriele I; Dawin, Eva; Bader, Verian; Haase, Stefanie; Kaisler, Johannes; David, Christina; Schneider, Ruth; Troisi, Riccardo; Zent, Daniel; Hegelmaier, Tobias; Dokalis, Nikolaos; Gerstein, Sara; Del Mare-Roumani, Sara; Amidror, Sivan; Staszewski, Ori; Poschmann, Gereon; Stühler, Kai; Hirche, Frank; Balogh, Andras; Kempa, Stefan; Träger, Pascal; Zaiss, Mario M; Holm, Jacob Bak; Massa, Megan G; Nielsen, Henrik Bjørn; Faissner, Andreas; Lukas, Carsten; Gatermann, Sören G; Scholz, Markus; Przuntek, Horst; Prinz, Marco; Forslund, Sofia K; Winklhofer, Konstanze F; Müller, Dominik N; Linker, Ralf A; Gold, Ralf; Haghikia, Aiden.
Afiliación
  • Duscha A; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • Gisevius B; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • Hirschberg S; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • 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.
  • Stangl GI; Institute of Agricultural and Nutritional Sciences, Martin Luther University, Halle-Wittenberg 06108, Germany.
  • 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.
  • Bader V; Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum 44801, Germany.
  • Haase S; Department of Neurology, University of Regensburg, Regensburg 93053, Germany.
  • Kaisler J; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • David C; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • Schneider R; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • Troisi R; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • Zent D; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • Hegelmaier T; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • Dokalis N; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Hirche F; Institute of Agricultural and Nutritional Sciences, Martin Luther University, Halle-Wittenberg 06108, Germany.
  • 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.
  • Kempa S; Integrative Metabolomics and Proteomics, Berlin Institute of Medical Systems Biology/Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
  • Träger P; Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University (FAU) Erlangen-Nürnberg, Erlangen 91054, Germany.
  • Zaiss MM; Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University (FAU) Erlangen-Nürnberg, Erlangen 91054, Germany.
  • Holm JB; Clinical Microbiomics A/S, Copenhagen 2200, Denmark.
  • 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.
  • Nielsen HB; Clinical Microbiomics A/S, Copenhagen 2200, Denmark.
  • Faissner A; Department of Cell Morphology and Molecular Neurobiology, Ruhr University Bochum, Bochum 44801, Germany.
  • Lukas C; Department of Radiology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • Gatermann SG; Department of Medical Microbiology, Ruhr University Bochum, Bochum 44801, Germany.
  • Scholz M; Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig 04109, Germany.
  • Przuntek H; Clinic of Neurology II, EVK Hattingen, Hattingen 45525, Germany.
  • 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 79
  • 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.
  • Winklhofer KF; Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum 44801, Germany.
  • 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.
  • Linker RA; Department of Neurology, University of Regensburg, Regensburg 93053, Germany.
  • Gold R; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany.
  • Haghikia A; Department of Neurology, Ruhr University Bochum, St. Josef Hospital Bochum, Bochum 44791, Germany. Electronic address: aiden.haghikia@rub.de.
Cell ; 180(6): 1067-1080.e16, 2020 03 19.
Article en En | MEDLINE | ID: mdl-32160527
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Propionatos / Esclerosis Múltiple Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Propionatos / Esclerosis Múltiple Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos