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EXPERT REACTION: Salty diets may raise blood pressure by killing off gut bacteria

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Salt could be linked to high blood pressure because of the effect it has on gut bacteria, according to research by German scientists. They found that a high-salt diet reduced Lactobacillus bacteria in mice and increased production of immune cells linked to high blood pressure, and a pilot study in humans found similar results. When the salty mice had their guts replenished with the lost bacteria, the effects were reversed. The researchers suggest medical trials in humans would determine whether probiotics might prevent or treat salt-related conditions such as high blood pressure.

Journal/conference: Nature

DOI: 10.1038/nature24628

Organisation/s: Max-Delbrück Center for Molecular Medicine, Germany

Funder: German Centre for Cardiovascular Research; Center for Microbiome Informatics and Therapeutics; MetaCardis consortium; German Research Foundation; Novartis Pharma; European Research Council (ERC); SALK-grant from the government of Flanders, Belgium; Odysseus-grant of the Research Foundation Flanders.

Media Release

From: Springer Nature

Biology: Gut microbes worth their salt

High salt intake alters the gut microbiota in mice reports a study published online in Nature this week. As the role of gut microbiota in disease is becoming increasingly recognized, these findings highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions.

High salt consumption associated with a Western lifestyle can lead to hypertension and cardiovascular disease. It may also drive autoimmunity by inducing pro-inflammatory T helper 17 (TH17) cells, which have also been linked to hypertension.

To determine the effect of high salt consumption on the composition of the gut microbiota, Dominik Müller and colleagues analysed faecal samples from mice fed a normal salt diet (NSD) and a high salt diet (HSD). The authors found that by day 14, several microbial species were significantly decreased in HSD-fed mice. They then used 16S ribosomal DNA gene sequencing and computational approaches to identify the most important bacterial groups that decreased when mice were fed a HSD and found that a member of the genus Lactobacillus (Lactobacillus murinus), was most strongly associated with HSD.

Further work demonstrated that administration of L. murinus to mice reduced TH17 cells and prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis (a mouse model of brain inflammation) and salt-sensitive hypertension. In line with these findings, a small pilot study in healthy humans found that increased salt intake reduces intestinal survival of multiple Lactobacillus species, accompanied by an increase in TH17 cells and elevated blood pressure; although further investigation in humans is required.

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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Brian J. Morris is Professor Emeritus of the School of Medical Sciences and Bosch Institute at the University of Sydney

The role of our gut bacteria in diseases ranging from cardiovascular to cancer has come to the fore in recent years.

Earlier this year a study from the Baker Institute in Melbourne published in the top cardiovascular journal, Circulation, showed that a diet high in fibre increased the abundance of bacteria that produce acetate. This was able to lower blood pressure and heart disease in mice.

Now, in a new study published today in Nature, researchers in Germany showed that a diet high in salt, typical of Western countries and long implicated in hypertension, also affects the spectrum of bacterial species in the gut – the gut microbiome. A high salt diet was able to virtually wipe out the healthy Lactobaccilus species in the gut.

This led to a rise in the immune system mediator interleukin A, which raised levels of key inflammatory cells known as TH17 cells, increased inflammation in blood vessels and led to blood pressure going up.

People with a healthy traditional diet have high Lactobaccilus in their gut, but the high salt diet of people in more affluent countries probably explains why they have low Lactobaccilus levels and an epidemic of hypertension, as well as various autoimmune diseases.

Studies have shown that taking probiotics rich in Lactobaccilus can lower blood pressure in people with hypertension.

Large, well-controlled randomized clinical trials are now warranted to test whether boosting Lactobacillus can help stem the tide of rampant hypertension in our society.

But of course, if governments took the advice of health authorities and legislated against high salt and junk food generally, e.g., by massive taxes as proven effective in reducing tobacco consumption in Australia, we would see a reduction in not only hypertension but the scourge of obesity, diabetes, many cancers and cardiovascular diseases generally.

Last updated: 15 Nov 2017 2:39pm

Dr Francine Marques is a National Heart Foundation Future Leader Fellow and Baker Fellow at Baker Heart & Diabetes Institute

This is an exciting and fast moving field, and as I said in the talk I gave this afternoon at the American Heart Association scientific sessions, we are still in our baby steps to fully understand the role of the gut microbiota in complex diseases such as hypertension.

The study by Wilck and colleagues adds to this important puzzle by characterising the changes in the gut microbiome after the intake of a high salt diet, which is known to increase blood pressure.

These findings, however, are not surprising considering we have known for a while that the prox­imal colon is an important site for dietary sodium absorption (as I wrote recently in our review in Nature Reviews Cardiology).

In this study, the authors determined that a high salt diet changed several types of microbes in the gut, in particular the levels of the bacteria Lactobacillus murinus (a rodent-specific species), which was also inhibited in the presence of salt in vitro.

They also observed that a high salt diet increased the numbers of a pro-inflammatory immune cell type, called T helper 17, in the spleen, and daily treatment with L. murinus was able to lower it.

Similarly to high salt intake, these same cells had been previously implicated in the development of hypertension.

In terms of blood pressure, as expected, the high salt diet increased blood pressure, but the authors were able to produce a very small (but significant) reduction in systolic and diastolic blood pressure when the mice were treated with L. murinus.

But how about in humans? Similarly to mice, in a small group of 8 subjects that received salt tablets on top of their normal diet for 14 days, there was an increase in blood pressure (as expected) and a decrease in T helper 17 cells.

They also looked into the amount of Lactobacillus species (since L. murinus is not found in humans) in faecal samples of these subjects before and after the added salt. Important here is that this genus is not highly abundant in the human gut, and not present at all in the gut of some people (in their study only ~40% had this genus). In this study, most of the species had been lost at the end of the salt challenge in the subjects that originally had Lactobacillus.

Lactobacillus can be found in several foodstuff including yogurt and some types of cheese, and some strains help us digest lactose present in milk.

This study adds to the puzzle of the gut microbes in hypertension and highlights another way blood pressure could be regulated by gut microbes – adding to our recent findings related to fibre and its metabolites.

There was, however, no molecular mechanism proposed between salt, Lactobacillus and levels of T helper 17 cells, which was a bit disappointing, but I am sure other studies will address this limitation.

In future studies, it would be interesting to determine, in the hypertensive community, whether the lack of Lactobacillus species is generally low or absent, as this may have implications for treatment.

Last updated: 15 Nov 2017 2:17pm
Dr Hannah Wardill is from the Adelaide Medical School (Cancer Treatment Toxicities Group) at the University of Adelaide, as well as the Centre for Nutrition and Gastrointestinal Disease South Australian Health and Medical Research Institute (SAHMRI)

Your gut is home to trillions of bacteria. In fact, there are more bacteria in your gut than there are cells in your body, meaning we are all more bug than human!

As we begin to scratch the surface of this fascinating ecosystem, the biggest question on everyone’s mind is why are they there, and what are they doing.
 
One of the biggest roles these gut bacteria play is regulation of a person’s immune system. Higher levels of good bacteria are associated with a more tolerant immune system, whilst bad bacteria are thought to drive a more aggressive immune response associated with a process called inflammation.

This interaction between the gut and immune system is now at the centre of new findings, published in Nature, linking gut bacteria with cardiovascular health.
 
Authors reported that salt intake, a major risk factor for cardiovascular disease, changed the types of the gut bacteria in both mice and humans. They showed a decrease in a particular species of “good bacteria” called Lactobacillus following salt consumption. 
 
This exciting research is the first to suggest that gut bacteria might act as the middle-man between salt and heart health, and provides a new therapeutic target to counteract salt-sensitive diseases.

Last updated: 15 Nov 2017 12:22pm

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    Lactobacillus murinus under the microscope.

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    Dr Nicola Wilck at the lab bench.

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    Dr Nicola Wilck at the flow cytometer.

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    The amount of salt in a person's diet affects populations of cells in the gut. High levels of salt increase the numbers of Th17 immune cells (RED) but lower the number of lactobacilli (BLUE).

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