We all know that too much salt in the diet isn’t good for health. High salt levels can lead to high blood pressure and cardiovascular disease. New studies in mice and humans by researchers in Germany, the U.S. and Belgium, have now shown that high levels of dietary salt also strip the microbiome of specific bacteria. The results suggest that taking tailored probiotics to replace the missing bacteria could help to reduce hypertension induced by a diet high in salt and have more wide-ranging benefits, possibly even as an addition to existing therapies for autoimmune disorders.
“Multiple sclerosis may be one of the salt-sensitive diseases that we might be able to treat in the future with individually tailored probiotics as add-on to standard immune therapies,” states co-researcher Prof. Ralf Linker, a professor in the department of neurology, Friedrich-Alexander-University Erlangen-Nuremberg, Germany. The interdisciplinary research team reports its findings in Nature, in a paper entitled “Salt-responsive gut commensal modulates TH17 axis and disease.”
High dietary salt levels have been found to induce proinflammatory T helper 17 (TH17) cells, which have been linked with hypertension and also play a damaging role in certain autoimmune disorders. Changes in diet can also lead to either temporary or long-term changes to gut microbiome composition, which can have “profound effects” on T cells, the researchers write. “TH17 cells are particularly affected by the abundance of specific commensal bacteria.”
What hasn’t been studied before is the direct effect of dietary salt on the gut microbiome, notes Dominik Müller, Ph.D., at the Berlin Experimental and Clinical Research Center (ECRC) and the Berlin Institute of Health (BIH) within the Max Delbrück Center for Molecular Medicine and the Charité – Universitätsmedizin Berlin. The researchers, headed by Müller’s team, compared the gut microbiomes of mice fed either a normal or high-salt diet.
Their results showed that high levels of dietary salt caused gut populations of Lactobacillus species to drop dramatically, in parallel with the animals developing higher blood pressure and producing increased numbers of TH17 cells. However, when animals fed a high-salt diet were also given oral probiotics of Lactobacillus murinus, their blood pressure levels and numbers of TH17 cells dropped. “Thus, L. murinus prevents HSD [high-salt diet]-induced generation of TH17 cells and consequently ameliorates salt-sensitive hypertension,” the authors write.
A high-salt diet also worsened the symptoms of disease in mice with experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Again, adding the Lactobacillus probiotic to the high-salt diet ameliorated the EAE symptoms.
The team then carried out a small-scale study in human volunteers to investigate the effects of increased dietary salt intake on blood pressure and the gut microbiome. Healthy male participants were given oral slow-release salt tablets, which they took in addition to their regular diets, and which roughly doubled their intake of salt. After two weeks of this high-salt intake, the volunteers exhibited higher blood pressure and increased numbers of TH17 helper cells in blood samples. Analysis of fecal samples also showed that the their gut microbiomes were almost completely denuded of Lactobacillus. “After the high-salt challenge, nine out of ten Lactobacillus populations that were initially present could no longer be detected in the respective study subjects, suggesting a loss of Lactobacillus species,” the authors comment.
They acknowledge that the human study demonstrated limited power and the results will need validating in larger numbers of people. However, the findings do suggest that even modest increases in salt can affect intestinal Lactobacillus strains, and lead to increased levels of proinflammatory TH17 cells and blood pressure changes. “Compared to microbiomes from indigenous populations, abundance of Lactobacillus strains in ‘Western’ gut microbiomes is low,” the authors add. “Salt ingestion that already starts at a young age may partially have contributed to the relative loss of Lactobacillus strains from Western microbiomes and thereby may have a role in the development of hypertension and autoimmunity.”
These results don’t directly point to a therapeutic effect of lactobacilli, and additional trials will also be needed to investigate the potential use of probiotics against salt-related disorders. “Our study goes beyond just describing the changes caused by salt,” Prof. Müller notes. “We want to consider interrelated processes.” Nevertheless, the identification of Lactobacillus as what the team calls “a natural inhibitor of high salt-induced TH17 cells in mice” could feasibly serve as a foundation for new preventive or therapeutic approaches. The team is now planning a larger-scale, double-blind, placebo-controlled human blood pressure study at the ECRC.