Common salt reduces the number of certain lactic acid bacteria in the gut of mice and humans according to a study published in Nature by Berlin’s Max Delbrück Center and Charité. This has an impact on immune cells which are partly responsible for autoimmune diseases and hypertension. Probiotics ameliorate the symptoms of disease in mice.
We eat salt every day, sometimes more, sometimes less, but often too much. “But so far, nobody had studied how salt affects the bacteria in the gut,” says head of the study Professor Dominik Müller of the Berlin Experimental and Clinical Research Center (ECRC) and the Berlin Institute of Health (BIH), both of which are joint institutions within the Max Delbrück Center for Molecular Medicine and the Charité – Universitätsmedizin Berlin.
Lactobacilli offset the harmful effects of salt
Too much salt in food can encourage hypertension and might even have a negative impact on the course of autoimmune diseases like multiple sclerosis (MS). Now Müller and his team have demonstrated that excess salt decimates the lactobacilli in the gut while blood pressure rises and the number of Th17 helper cells is increased. These immune cells are associated with hypertension and autoimmune diseases like MS.
When the animals were given probiotic lactobacilli in addition to the high-salt diet, however, the frequency of TH17 helper cells decreased once again and blood pressure dropped. The probiotics also alleviated the clinical symptoms of experimental autoimmune encephalomyelitis, a disease model for MS.
The researchers thus identified the microbiome as an important factor in diseases affected by salt. The lead author and ECRC scientist Dr Nicola Wilck says, “Gut bacteria influence the host organism, and the immune system is also very active in the gut.”
Müller and Wilck worked together with an interdisciplinary research team including Professor Ralf Linker from FAU Nürnberg-Erlangen, scientists from Massachusetts Institute of Technology (MIT) in Boston, USA, from the European Molecular Biology Laboratory (EMBL), Heidelbelberg, the University of Regensburg, and the Vlaams Instituut voor Biotechnologie (VIB) in Hasselt, Belgium. The German Centre for Cardiovascular Research (DZHK) also supported the study.
Pilot study with human test subjects
Apart from the experiments on mice, the researchers also investigated the bacterial community in the digestive tract of twelve healthy men who were given six extra grams of salt every day for a fortnight. As the test subjects otherwise maintained their usual eating habits, they thus roughly doubled their daily intake of salt. Here, too, the lactobacilli responded sensitively. Most of them were no longer detectable after 14 days of increased salt intake. At the same time, scientists discovered that the probands’ blood pressure rose and the number of Th17 helper cells in the blood increased.
Pathbreaking discoveries for therapy
The role played by bacteria in the most diverse diseases is becoming an ever more important focus of research. Just how the organism interacts with gut flora is, however, still largely unknown. “Our study goes beyond just describing the changes caused by salt. We want to consider interrelated processes,” says Müller. But so far, they have not managed to completely elucidate the precise interactions, he explains. “We can’t exclude the possibility that there are other salt-sensitive bacteria that are just as important.”
The new findings have not actually confirmed the therapeutic effect of lactobacilli which are found in fermented food such as sauerkraut, yogurt and cheese. Neuroimmunologist Professor Ralf Linker notes, “Multiple sclerosis may be one of the salt-sensitive diseases which we might be able to treat in the future with individually-tailored probiotics as add-on to standard immune therapies.” Lactobacillus probiotics of this kind have therapeutic potential.
This will soon all be examined at ECRC, says Wilck. “We are planning a blood pressure study with human subjects: double blind with a larger number of participants of both genders and placebo controlled.” After that, they can start thinking about the therapeutic application of probiotics.
- International Study: Excess Dietary Salt May Drive the Development of Autoimmune Diseases (MDC Press Release, March 7, 2013)
- “Hypertension-caused End-Organ Damage” – Website by the lab of Dominik Müller and Ralf Dechend at the MDC
- “Multiple Sklerose und Neuroimmunologie” – Website by the lab of Ralf Linker, FAU Erlangen (German only)
- “Engineering the Human Microbiome” – Website der AG Eric Alm am MIT in Boston
Nicola Wilck1,2,3,4,5, Mariana G. Matus6,7, Sean M. Kearney6, Scott W. Olesen6, Kristoffer Forslund8, Hendrik Bartolomaeus1,2,3,4, Stefanie Haase9, Anja Mähler1,5, András Balogh1,2,3,4,5, Lajos Markó1,2,3,4,5, Olga Vvedenskaya3,10,11, Friedrich H. Kleiner1, Dmitry Tsvetkov1,2, Lars Klug1,5, Paul I. Costea8, Shinichi Sunagawa8,12, Lisa Maier13, Natalia Rakova1,9 , Valentin Schatz14, Patrick Neubert14, Christian Frätzer15, Alexander Krannich5, Maik Gollasch1,2,3, Diana A. Grohme16, Beatriz F. Côrte-Real22, Roman G. Gerlach17, Marijana Basic18, Athanasios Typas13, Chuan Wu19, Jens M. Titze20, Jonathan Jantsch14, Michael Boschmann1,5, Ralf Dechend1,2,4, Markus Kleinewietfeld16,21,22, Stefan Kempa3,5,10, Peer Bork3,8,23,24, Ralf A. Linker9*, Eric J. Alm6*, Dominik N. Müller1,2,3,4,5*(2017): „Salt-responsive gut commensal modulates TH17 axis and disease.“ Nature. doi:10.1038/nature24628
1Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin; 2Charité-Universitätsmedizin Berlin; 3Max-Delbrück Center for Molecular Medicine in the Helmholtz Association; 4DZHK (German Centre for Cardiovascular Research), partner site Berlin; 5Berlin Institute of Health (BIH), Berlin; 6Center for Microbiome Informatics and Therapeutics, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; 7Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; 8European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg; 9Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen; 10Integrative Proteomics and Metabolomics Platform, Berlin Institute for Medical Systems Biology BIMSB, Berlin; 11Berlin School of Integrative Oncology, Charité University Medicine Berlin; 12Institute of Microbiology, ETH Zurich, Zurich, Switzerland; 13European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg; 14Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, Regensburg; 15Lipidomix GmbH, Berlin; 16Translational Immunology, Department of Clinical Pathobiochemistry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden; 17Project Group 5, Robert Koch Institute, Wernigerode; 18Hannover Medical School, Institute for Laboratory Animal Science and Central Animal Facility, Hannover; 19Experimental Immunology Branch, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA; 20Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; 21Center for Regenerative Therapies Dresden (CRTD), Dresden; 22VIB Laboratory of Translational Immunomodulation, VIB Center for Inflammation Research (IRC), UHasselt, Diepenbeek, Belgium; 23Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg; 24Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg
* These authors contributed equally to this work.