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.
(1 из 1) Editorial www.thelancet.com/gastrohep Vol 4 February 2019 81 Dennis Kunkel Microscropy/Science Photo Library For the study by Suez and colleagues see Cell 2018; 174: 1406–23 For the study by Zmora and colleagues see Cell 2018; 174: 1388–405 For the study by Freedman and colleagues see N Engl J Med 2018; 379: 2015–26 For the study by Schnadower and colleagues see N Engl J Med 2018; 379: 2002–14 Probiotics: elixir or empty promise? The gut microbiota has been implicated in diseases ranging from obesity to Parkinson’s disease and de pression. Little wonder then that commercial probiotics have gained widespread popularity and are now estimated to command a US$37 billion market worldwide. But with research into the microbiome still in its infancy, increasing evidence suggests that both commercial and clinical use of probiotics is outpacing the science. Evidence from clinical trials is mixed and often of low quality, but findings from meta analyses suggest that probiotics can pro vide benefits in the treatment of some conditions, such as infectious and antibiotic associated diarrhoea. As such, taking probiotics after antibiotic treatment is an increasingly common practice. However, two studies recently reported in Cell question whether taking highly concentrated supplements of so called good bacteria aids the reco very of normal gut flora. Suez and colleagues investigated the recovery of the gut microbiota after antibiotic treatment and found that probiotics might perturb rather than aid this process. The probiotics rapidly colonised the gut but prevented the normal microbiota from repopulating for up to 5 months. While likely to be considerably less appealing, the group who received autologous faecal microbiota transplanta tion recovered their microbiota the quickest, with the composition of the microbiota returning to normal within days. Furthermore, Zmora and colleagues showed that colonisation occurred in highly individualised patterns, with some people’s gastrointestinal tracts rejecting probiotics and others allowing colonisation by the probiotic strain, meaning that many individuals taking probiotic supplements are simply wasting their money. Two large scale clinical trials recently reported in the New England Journal of Medicine suggest that the situation in infectious diarrhoea might also be more complex than previously believed. Freedman and colleagues did a randomised controlled trial of a probiotic contain ing Lactobacillus rhamnosus and Lactobacillus helveticus in children presenting to the emergency department with gastroenteritis. Contrary to expectations, they found that the probiotic did not prevent development of moderate to severe gastroenteritis within 14 days after enrolment. In a separate study, Schnadower and colleagues found similar results with L rhamnosus GG alone. Both trials used probiotics that are available over the counter in North America and showed no significant difference from placebo in the duration of diarrhoea and vomiting, number of unscheduled health care visits, or length of absence from day care. These results cannot be generalised to other probiotic strains or preparations, but they do show that we have some way to go in elucidat ing which probiotics might provide benefits in which clinical settings. Importantly, patients with gastrointestinal conditions are not the only ones taking probiotics. 3·9 million people in the USA alone regularly take probiotic supplements, with promised benefits ranging from improved digestion and immune function to improved mental health and prevention of heart disease. However, evidence for these benefits is lacking, and because probiotics are often sold as supplements, manufacturers in many countries are not required to provide evidence of their safety and efficacy to regulatory bodies. The ubiquity of probiotic products would suggest that, at worst, they are harmless. Nevertheless, some safety concerns have been raised, including the risk of contamination, possibility of fungaemia or bacteraemia (particularly in immune compromised, elderly, or critic ally ill individuals), small intestinal bacterial ov ergrowth, and antibiotic resistance. Adding to concerns, clinical trials of probiotics have not consistently reported safety outcomes. While the logic behind probiotics might seem sound, it is clear that we have a long way to go before understanding the complexity of the microbiota and the effects—both good and bad—that probiotics might have. All individuals have a unique gut microbiome, and the effects of different bacteria on different people are likely to be highly variable; as such, probiotic use might even need to be personalised for optimal benefits. Commercially available products might not contain the correct strains or quantities of bacteria to provide benefits, and most probiotic supplements contain only single strains, vastly oversimplifying the complexity of the microbiota. While taking a supplement for improved health is certainly an attractive prospect, those looking to aid their gut microbiota might be better served by consuming a healthy, varied diet. In the meantime, rigorous clinical trials are needed to substantiate potential health benefits and to confirm whether probiotics are elixirs or just empty promises. ■ The Lancet Gastroenterology & Hepatology
