Salt-responsive gut commensal modulates TH17 axis and disease

Nicola Wilck, Mariana G. Matus, Sean M. Kearney, Scott W. Olesen, Kristoffer Forslund, Hendrik Bartolomaeus, Stefanie Haase, Anja Mähler, András Balogh, Lajos Markó, Olga Vvedenskaya, Friedrich H. Kleiner, Dmitry Tsvetkov, Lars Klug, Paul I. Costea, Shinichi Sunagawa, Lisa Maier, Natalia Rakova, Valentin Schatz, Patrick Neubert, Christian Frätzer, Alexander Krannich, Maik Gollasch, Diana A. Grohme, Beatriz F. Côrte-Real, Roman G. Gerlach, Marijana Basic, Athanasios Typas, Chuan Wu, Jens M. Titze, Jonathan Jantsch, Michael Boschmann, Ralf Dechend, Markus Kleinewietfeld, Stefan Kempa, Peer Bork, Ralf A. Linker, Eric J. Alm () and Dominik N. Müller ()
Additional contact information
Nicola Wilck: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Mariana G. Matus: Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology
Sean M. Kearney: Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology
Scott W. Olesen: Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology
Kristoffer Forslund: European Molecular Biology Laboratory, Structural and Computational Biology Unit
Hendrik Bartolomaeus: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Stefanie Haase: Friedrich-Alexander-University Erlangen-Nuremberg
Anja Mähler: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
András Balogh: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Lajos Markó: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Olga Vvedenskaya: Max-Delbrück Center for Molecular Medicine in the Helmholtz Association
Friedrich H. Kleiner: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Dmitry Tsvetkov: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Lars Klug: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Paul I. Costea: European Molecular Biology Laboratory, Structural and Computational Biology Unit
Shinichi Sunagawa: European Molecular Biology Laboratory, Structural and Computational Biology Unit
Lisa Maier: European Molecular Biology Laboratory, Genome Biology Unit
Natalia Rakova: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Valentin Schatz: Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg
Patrick Neubert: Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg
Christian Frätzer: Lipidomix GmbH
Alexander Krannich: Berlin Institute of Health (BIH)
Maik Gollasch: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Diana A. Grohme: Translational Immunology, Medical Faculty Carl Gustav Carus, Technical University of Dresden
Beatriz F. Côrte-Real: VIB Laboratory of Translational Immunomodulation, VIB Center for Inflammation Research (IRC), Hasselt University, Campus Diepenbeek
Roman G. Gerlach: Project Group 5, Robert Koch Institute
Marijana Basic: Hannover Medical School, Institute for Laboratory Animal Science and Central Animal Facility
Athanasios Typas: European Molecular Biology Laboratory, Genome Biology Unit
Chuan Wu: Experimental Immunology Branch, National Cancer Institute, US National Institutes of Health
Jens M. Titze: Vanderbilt University School of Medicine
Jonathan Jantsch: Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg
Michael Boschmann: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Ralf Dechend: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin
Markus Kleinewietfeld: Translational Immunology, Medical Faculty Carl Gustav Carus, Technical University of Dresden
Stefan Kempa: Max-Delbrück Center for Molecular Medicine in the Helmholtz Association
Peer Bork: Max-Delbrück Center for Molecular Medicine in the Helmholtz Association
Ralf A. Linker: Friedrich-Alexander-University Erlangen-Nuremberg
Eric J. Alm: Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology
Dominik N. Müller: Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin

Nature, 2017, vol. 551, issue 7682, 585-589

Abstract: Abstract A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (TH17) cells, which can also contribute to hypertension. Induction of TH17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating TH17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased TH17 cells and increased blood pressure. Our results connect high salt intake to the gut–immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions.

Date: 2017
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DOI: 10.1038/nature24628

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