image: This is Dr Nicola Wilck at the lab bench. view more
Credit: Müller lab, MDC
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), Heidelberg, 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.
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Nicola Wilck et al. (2017): "Salt-responsive gut commensal modulates TH17 axis and disease." Nature. doi:10.1038/nature24628
About the Max Delbrück Center for Molecular Medicine (MDC)
The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) was founded in Berlin in 1992. It is named for the German-American physicist Max Delbrück, who was awarded the 1969 Nobel Prize in Physiology and Medicine. The MDC's mission is to study molecular mechanisms in order to understand the origins of disease and thus be able to diagnose, prevent and fight it better and more effectively. In these efforts the MDC cooperates with the Charité - Universitätsmedizin Berlin and the Berlin Institute of Health (BIH) as well as with national partners such as the German Center for Cardiovascular Research and numerous international research institutions. More than 1,600 staff and guests from nearly 60 countries work at the MDC, just under 1,300 of them in scientific research. The MDC is funded by the German Federal Ministry of Education and Research (90 percent) and the State of Berlin (10 percent), and is a member of the Helmholtz Association of German Research Centers. http://www.mdc-berlin.de
About Charité - Universitätsmedizin Berlin
With a total of 3,011 beds, Charité - Universitätsmedizin Berlin is one of the largest university hospitals in Europe. Charité spans 4 campuses and comprises approximately 100 Departments and Institutes. In 2015, Charité treated more than 146,000 outpatient and more than 694,000 inpatient cases. With approximately 17,100 staff employed across the Charité group of companies, Charité is one of the largest employers in Berlin. In 2016, the Charité university hospital recorded a turnover of more than €1.6 billion. The areas of research, teaching, and health care delivery are intricately linked, resulting in a working relationship that is characterized by interdisciplinary cooperation. In 2016, Charité was able to secure more than €153 million in third-party funding, as well as approximately €202 million in state funding for research and teaching. With approximately 7,000 future physicians and dentists currently enrolled in degree courses, Charité is one of the largest medical faculties in Germany. http://www.charite.de/
Journal
Nature