A high-salt diet (HSD) reduced the numbers of certain bacterial species in mice, in particular Lactobacillus spp. This led to an increase in the number of inflammatory T-helper 17 (TH17) cells and raised blood pressure in the animals.
Supplementation with the probiotic Lactobacillus murinus reduced the number of TH17 cells in the mice and lowered their blood pressure. The probiotic treatment also alleviated experimental autoimmune encephalomyelitis (EAE) in the mice, found the multi-institutional research team led by the Max Delbrück Centre for Molecular Medicine (MDCMM), Berlin.
Other institutions involved in the study included Massachusetts Institute of Technology and the Friedrich-Alexander University (FAU), Erlangen-Nuremberg, Erlangen.
The scientists also conducted a pilot study in 12 humans, in which an HSD induced significant reductions in Lactobacillus species together with higher numbers of TH17 cells and elevated blood pressure.
When the subjects were given a probiotic one week prior to commencing the HSD, their Lactobacillus levels and blood pressure remained unaltered.
“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,” wrote the authors.
“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,” they added.
High intakes of salt, containing the mineral sodium, are known to raise blood pressure, and are also associated with cardiovascular disease and stroke.
The results suggest that gut microbiome may be a potential target in counteracting salt-sensitive conditions such as high blood pressure.
“Our experimental data in mice suggest that the gut microbiota might serve as a potential target to counteract salt- sensitive conditions. The identification of Lactobacillus as a ‘natural inhibitor’ of high salt-induced TH17 cells in mice could serve as a basis for the development of novel prevention and treatment strategies,” explained the researchers.
Additionally, the finding that probiotic therapy was improved EAE in mice may have implications for other autoimmune diseases such as multiple sclerosis (MS).
"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," commented Professor Dr.Ralf Linker of FAU.
Nevertheless, since the EAE was actively induced in the mice in this study, the treatment may not necessarily be extendable to spontaneous disease conditions, the researchers cautioned.
Furthermore, the findings should not be construed as a licence to eat a poor diet, warns joint senior author Professor Erik Alm of MIT.
"I think certainly there's some promise in developing probiotics that could be targeted to possibly fixing some of the effects of a high-salt diet, but people shouldn't think they can eat fast food and then pop a probiotic, and it will be cancelled out," he said.
In the mouse study, the animals were fed table salt as 4% of their diet (compared with the normal dietary content of 0.5%) for two weeks.
The scientists also found that another species of Lactobacillus (L.reuteri) also provided similar protective effects in the mice, although the non-Lactobacillus strain E.coli Nissle 1917 did not.
In the human pilot study, the 12 subjects were given an additional 6 grams/day for two weeks.
Although results were promising, the trial was an ‘open-label’ design, with a small number of subjects. The researchers are therefore looking at a further trial to confirm the therapeutic effect of Lactobacillus, which is found in fermented food such as sauerkraut, yogurt and cheese.
"We are planning a blood pressure study with human subjects: double blind with a larger number of participants of both genders and placebo controlled," said lead author Dr. Nicola Wilck of the Experimental and Clinical Research Centre, an institution within MDCMM.
Published online. DOI: 10.1038/nature24628
“Salt-responsive gut commensal modulates TH17 axis and disease”
Authors: Nicola Wilck, Ralf A. Linker, Eric J. Alm, Dominik N. Müller et al