puc-header

Propionic Acid Shapes the Course of Multiple Sclerosis by a Distinct Immunomodulatory and Neuroprotective Mechanism

51 Pages Posted: 3 Dec 2018 Publication Status: Published

See all articles by Alexander Duscha

Alexander Duscha

Ruhr University of Bochum - Department of Neurology

Barbara Gisevius

Ruhr University of Bochum - Department of Neurology

Sarah Hirschberg

Ruhr University of Bochum - Department of Neurology

Stefanie Haase

University of Regensburg - Department of Neurology

Gabriele I. Stangl

Martin-Luther-Universität Halle-Wittenberg, Institut Agrar- und Ernährungswissenschaften

Johannes Berg

Ruhr University of Bochum - Department of Neurology

Christina David

Ruhr University of Bochum - Department of Neurology

Ruth Schneider

Ruhr University of Bochum - Department of Neurology

Nikolaos Dokalis

University of Freiburg - Institute of Neuropathology

Ori Staszewski

University of Freiburg - Institute of Neuropathology

Marcus May

Ruhr University of Bochum - Department of Cell Morphology and Molecular Neurobiology

Gereon Poschmann

Heinrich Heine University Dusseldorf - Institute for Molecular Medicine

Kai Stühler

Heinrich Heine University Dusseldorf - Institute for Molecular Medicine

Frank Hirche

Martin-Luther-Universität Halle-Wittenberg, Institut Agrar- und Ernährungswissenschaften

Andras Balogh

Max-Delbrück-Center for Molecular Medicine

Stefan Kempa

Max-Delbrück-Center for Molecular Medicine - Integrative Metabolomics and Proteomics

Jacob Bak Holm

Clinical Microbiomics A/S

Megan G. Massa

University of California, Los Angeles (UCLA) - Department of Integrative Biology and Physiology

Henrik Bjørn Nielsen

Clinical Microbiomics A/S

Andreas Faissner

Ruhr University of Bochum - Department of Cell Morphology and Molecular Neurobiology

Dominik N. Müller

Max-Delbrück-Center for Molecular Medicine

Carsten Lukas

Ruhr University of Bochum - Department of Radiology

Sören G. Gatermann

Ruhr University of Bochum - Department of Medical Microbiology

Ralf A. Linker

University of Regensburg - Department of Neurology

Horst Przuntek

Evangelisches Krankenhaus - Clinic of Neurology II

Marco Prinz

University of Bonn - Institute of Neuropathology

Ralf Gold

Ruhr University of Bochum - Department of Neurology

Aiden Haghikia

Ruhr University of Bochum - Department of Neurology

More...

Abstract

Short chain fatty acids (SCFA) are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here we investigate the SCFA propionic acid (PA) in multiple sclerosis (MS) as a model of general autoimmune and neurodegenerative diseases. The serum and feces of MS patients exhibited significantly reduced PA-levels, which were associated with a reduction in diversity and abundance of SCFA-producing bacteria. In a proof-of-concept study, we supplemented PA to MS patients as add-on to immunotherapy. After two weeks of PA intake, we observed a significant and sustained increase of functionally competent Treg, while Th1 and Th17 significantly decreased. Retrospective analyses of up to 3years of PA-intake revealed a reduced annual relapse rate, stabilization of disability and reduced brain atrophy. In primary neurons, differentiated from MS patient-specific induced pluripotent stem cells, PA enhanced neurite regrowth after damage, similar to the Treg key cytokine interleukin-10. Our findings suggest that PA can serve as a potent immunomodulatory and neuroprotective supplement to approved MS drugs.

Suggested Citation

Duscha, Alexander and Gisevius, Barbara and Hirschberg, Sarah and Haase, Stefanie and Stangl, Gabriele I. and Berg, Johannes and David, Christina and Schneider, Ruth and Dokalis, Nikolaos and Staszewski, Ori and May, Marcus and Poschmann, Gereon and Stühler, Kai and Hirche, Frank and Balogh, Andras and Kempa, Stefan and Holm, Jacob Bak and Massa, Megan G. and Nielsen, Henrik Bjørn and Faissner, Andreas and Müller, Dominik N. and Lukas, Carsten and Gatermann, Sören G. and Linker, Ralf A. and Przuntek, Horst and Prinz, Marco and Gold, Ralf and Haghikia, Aiden, Propionic Acid Shapes the Course of Multiple Sclerosis by a Distinct Immunomodulatory and Neuroprotective Mechanism (November 30, 2018). Available at SSRN: https://ssrn.com/abstract=3293683 or http://dx.doi.org/10.2139/ssrn.3293683
This version of the paper has not been formally peer reviewed.

Alexander Duscha

Ruhr University of Bochum - Department of Neurology

Bochum
Germany

Barbara Gisevius

Ruhr University of Bochum - Department of Neurology

Bochum
Germany

Sarah Hirschberg

Ruhr University of Bochum - Department of Neurology

Bochum
Germany

Stefanie Haase

University of Regensburg - Department of Neurology

93040 Regensburg
D-93040 Regensburg, 93053
Germany

Gabriele I. Stangl

Martin-Luther-Universität Halle-Wittenberg, Institut Agrar- und Ernährungswissenschaften

Karl-Freiherr-von-Fritsch-Str. 4
Halle (Saale), Sachsen-Anhalt 06120
Germany

Johannes Berg

Ruhr University of Bochum - Department of Neurology

Bochum
Germany

Christina David

Ruhr University of Bochum - Department of Neurology

Bochum
Germany

Ruth Schneider

Ruhr University of Bochum - Department of Neurology

Bochum
Germany

Nikolaos Dokalis

University of Freiburg - Institute of Neuropathology

Fahnenbergplatz
Freiburg, D-79085
Germany

Ori Staszewski

University of Freiburg - Institute of Neuropathology

Fahnenbergplatz
Freiburg, D-79085
Germany

Marcus May

Ruhr University of Bochum - Department of Cell Morphology and Molecular Neurobiology

Universitätsstraße 150
Bochum, 44801
Germany

Gereon Poschmann

Heinrich Heine University Dusseldorf - Institute for Molecular Medicine

Düsseldorf
Germany

Kai Stühler

Heinrich Heine University Dusseldorf - Institute for Molecular Medicine

Düsseldorf
Germany

Frank Hirche

Martin-Luther-Universität Halle-Wittenberg, Institut Agrar- und Ernährungswissenschaften

Karl-Freiherr-von-Fritsch-Str. 4
Halle (Saale), Sachsen-Anhalt 06120
Germany

Andras Balogh

Max-Delbrück-Center for Molecular Medicine

Anna-Louisa-Karsch-Straße 2
Berlin, 10178
Germany

Stefan Kempa

Max-Delbrück-Center for Molecular Medicine - Integrative Metabolomics and Proteomics

Anna-Louisa-Karsch-Straße 2
Berlin, 10178
Germany

Jacob Bak Holm

Clinical Microbiomics A/S

Copenhagen
Denmark

Megan G. Massa

University of California, Los Angeles (UCLA) - Department of Integrative Biology and Physiology

612 Charles E. Young Drive East
Box 957246
Los Angeles, CA 90095-7246
United States

Henrik Bjørn Nielsen

Clinical Microbiomics A/S

Copenhagen
Denmark

Andreas Faissner

Ruhr University of Bochum - Department of Cell Morphology and Molecular Neurobiology

Universitätsstraße 150
Bochum, 44801
Germany

Dominik N. Müller

Max-Delbrück-Center for Molecular Medicine

Anna-Louisa-Karsch-Straße 2
Berlin, 10178
Germany

Carsten Lukas

Ruhr University of Bochum - Department of Radiology

Bochum
Germany

Sören G. Gatermann

Ruhr University of Bochum - Department of Medical Microbiology

Bochum
Germany

Ralf A. Linker

University of Regensburg - Department of Neurology

93040 Regensburg
D-93040 Regensburg, 93053
Germany

Horst Przuntek

Evangelisches Krankenhaus - Clinic of Neurology II

Bredenscheider Str. 54
Hattingen, 45525
Germany

Marco Prinz

University of Bonn - Institute of Neuropathology

Regina-Pacis-Weg 3
Bonn, D-53012
Germany

Ralf Gold

Ruhr University of Bochum - Department of Neurology

Bochum
Germany

Aiden Haghikia (Contact Author)

Ruhr University of Bochum - Department of Neurology ( email )

Bochum
Germany

Click here to go to Cell.com

Paper statistics

Abstract Views
1,786
Downloads
34
PlumX Metrics