Ketogenic diet: a definite impact on immune cells

Ketogenic diets consist of massively reducing the intake of carbohydrates while increasing lipids. Once metabolized by the liver, these fats then become the body’s primary source of energy. This type of diet is used to treat certain pathologies or as part of a slimming diet, but a new study, published in the journal Cell, reveals that it largely modifies the intestinal microbiota. However, the latter plays an essential role in the body ensuring, among other things, the proper functioning of our immune system.

The ketogenic diet was developed in the early 1920s to treat epilepsy. Indeed, the state of ketosis – due to the accumulation of certain metabolites in the body – made the symptoms of the disease disappear. This diet is sometimes used today as a complementary therapy to cancer treatments, but also as a diet for certain athletes and individuals wishing to lose weight. Namely, it is also the traditional diet for certain populations, such as the Inuit.

Dieting that upsets the intestinal flora

Due to its rapid weight loss effect, the ketogenic diet is particularly popular with the approach of summer. It also has protective properties against diabetes. Indeed, this diet gives pride of place to fats, so as to force the body to use these fatty substances rather than carbohydrates as a source of energy. These fats are then metabolized by the liver to become ketone bodies, including acetylacetonate and β-D-hydroxybutyrate, which will supply energy to the heart and the brain. This diet is therefore sometimes advised to preserve heart health.

Previous research has already revealed that diets high in fat induce changes in the intestinal flora, which can promote the appearance of metabolic diseases in mice. However, ketogenic diets, which are even richer in fat, are offered as a therapy to prevent or even treat certain diseases. Faced with this inconsistency, the team of Peter Turnbaugh, a specialist in microbiology and immunology at UC San Francisco and member of the Benioff Center for Microbiome Medicine, looked at the impact of ketone bodies on the intestinal microbiota.

To carry out their study, Turnbaugh and his colleagues, associated with the Nonprofit Nutrition Science Initiative, recruited and then followed 17 adult individuals of various body masses (non-obese, overweight or obese). For two months, their diet and exercise levels were carefully monitored and controlled.

During the first four weeks of the study, participants received either a “standard” diet consisting of 50% carbohydrates, 15% protein and 35% fat or a ketogenic diet comprising 5% carbohydrates, 15% protein and 80% fat. After four weeks, the two groups changed diets, to allow the researchers to examine how switching from one diet to another had changed the participants’ microbiota.

However, the analysis of microbial DNA from stool samples showed that the transition from a standard diet to a ketogenic diet had radically changed the proportions of certain bacterial phyla – Actinobacteria, Bacteroidetes and Firmicutes – in the intestines of the participants, with significant changes in 19 different bacterial genera. Bifidobacteria, relatively common probiotics, have shown the greatest decrease.

Towards a new treatment for autoimmune diseases

To better understand these microbial changes, the researchers exposed the mouse gut to different components of human microbiomes inherent in ketogenic diets; they then found that these altered microbial populations specifically reduced the level of Th17 lymphocytes. These T cells are essential for fighting infectious diseases, but they are also known to promote inflammation in autoimmune diseases like rheumatoid arthritis, multiple sclerosis or Crohn’s disease.

Subsequently, the researchers subjected the mice to different diets more or less high in fat and were able to confirm that the so-called “high fat” diets and the ketogenic diets had opposite effects on the intestinal microbiota. In other words, in mice, the microbiota reacts differently from a certain level of fat in the diet. In addition, when animals moved from a standard diet to an even tighter carbohydrate restriction, the gut microbes began to change, correlating with the gradual increase in ketone bodies.

The team then wanted to check whether the ketone bodies alone could cause changes in the intestinal microbiota: they, therefore, fed the mice directly with these compounds. As a result, even in mice that ate normal amounts of carbohydrates, the mere presence of these compounds was sufficient to observe many of the microbial changes specific to the ketogenic diet.

This discovery suggests that ketone bodies could be used as therapy for autoimmune diseases affecting the gut (such as Crohn’s disease or ulcerative colitis): ”  For many people, maintaining a strict diet, to Low carb or ketogenic is extremely difficult,  “says Turnbaugh. This type of diet – not always pleasant – is actually recommended for them to relieve symptoms. ”  If future studies confirm that the microbial changes caused by ketone bodies themselves have health benefits, this could make the therapeutic approach much more pleasant a taste point of view  .”