Cells: The ketogenic diet inhibits the growth of Bifidobacteria in the gut

New advances have been made in scientific research on the ketogenic diet. Today, Peter J. The latest research by the Turnbaugh team on the ketogenic diet was published. They found in human and mouse experiments that ketogenic diets are metabolized to produce ketones that selectively inhibit Bifidobacteria in the intestines, thereby reducing the level of inflammatory Th17 cells in the intestines. Moreover, a normal high-fat diet does not have this effect.

More valuablely, a similar change in gut microbiome can occur by feeding ketones to mice on a normal diet. This may be good news for people who can’t adapt to a ketogenic diet.

Dr. Qi Yan Ang is the first author of the paper, published in the journal Cell.

Cells: The ketogenic diet inhibits the growth of Bifidobacteria in the gut

Screenshot of the first page of the paper

Speaking of ketogenic diet I think we must not be unfamiliar.

It is not only a way of eating, but also used as a treatment for certain diseases. In addition, its potential in recent years to reduce inflammation, promote weight loss and heart health has led to a public interest.

However, the effects of the ketogenic diet on metabolism and immunity are still not very clear. That said, we may not know exactly how a ketogenic diet improves health.

To Turnbaugh’s confusion, however, is that the effects of a ketogenic diet and a high-fat diet on the human body seem to be at odds.

Because he notes that many studies have shown that high-fat diets are harmful to health and are closely related to metabolic diseases, but that a ketogenic diet with very low carbon water and very high fat is a way to prevent or even treat diseases.

What is the reason for this paradox? The Turnbaugh team speculates that this may be partly related to gut microbes.

Cells: The ketogenic diet inhibits the growth of Bifidobacteria in the gut

Peter J, who grows very tall. Turnbaugh

To confirm this hypothesis, the Turnbaugh team recruited 17 overweight or class-1 obese non-diabetic volunteers to conduct a cross-study at the hospital.

The researchers prepared two diets for the volunteers involved in the experiment, the first being a general diet (BD), with 50 percent carbon water, 15 percent protein and 35 percent fat, and the second being a ketogenic diet (KD), carbon water only 5 percent, protein or 15 percent, and fat accounting for 80 percent.

For the first four weeks of the trial, all the volunteers ate a regular diet, and by the fourth week, the researchers collected the volunteers’ faeces every day. After the end of the first round of the regular diet, a four-week ketogenic diet was followed, and by the fourth week, volunteers’ faeces were also collected daily.

The next thing to do is to sequence 16S rRNA for all the stool samples.

Sequencing results showed that two different diets had a significant effect on gut microbes. Compared with the normal diet, the ketogenic diet led to a decrease in the number of linebacteria in the volunteers’ intestines (and the genus Bifidobacteria in them) and the number of coliform bacteria. However, the burden on enterobacteria has not changed in general.

Cells: The ketogenic diet inhibits the growth of Bifidobacteria in the gut

Effects of ketogenic diet on gut microbes

Changes in enterobacteria also led to some changes in the metabolites of intestinal microorganisms, but there was no significant change in the level of short-chain fatty acids.

The researchers then studied the effects of a high-fat diet and a ketogenic diet on gut microbiomes in model mice. They found that a high-fat diet had a different effect on enterobacteria from a ketogenic diet, with the most notable difference being that a ketogenic diet led to a significant reduction in Bifidobacteria. Moreover, the ketogenic diet increased the levelof of beta-hydroxybutyric acid (beta-HB) in the blood of mice compared to other diets.

In addition, studies in mice showed that Bifidobacteria decreased as carbohydrate levels in food decreased.

Cells: The ketogenic diet inhibits the growth of Bifidobacteria in the gut

Photo: UCSF

So what is the mechanism of the different effects of a high-fat diet and a ketogenic diet on enterobacteria?

Although there have been some previous studies, none of the previous conclusions could explain what the Turnbaugh team found. Finally, the researchers decided to focus the study on ketones.

Because the level of ketones increases, is a sign of increased lipid oxidation in cases where carbon water intake is limited. Previous studies have found that the ketogenic diet increases levels of beta-hydroxybutyric acid, and that Bifidobacteria changes with the proportion of carbohydrates in food.

Although ketones are mainly produced by the liver, in recent years scientists have found that intestinal epithelial cells can actually produce ketones. There have even been studies that ketogenic dietary feeding can increase levels of beta-hydroxybutyric acid in the intestines.

Thus, there seems to be a looming link between the ketogenic diet, the gut ketones and Bifidobacteria.

Cells: The ketogenic diet inhibits the growth of Bifidobacteria in the gut

Relationship between the abundance of Bifidobacteria and food carbon water

To clarify the relationship, the researchers supplemented mice with synthetic ketoneests (KEEs) to mimic the beta-hydroxybutyric acid produced by the intestines without limiting carbohydrates in food. Finally, it was found that there was a negative correlation between the abundance of Bifidobacteria and the level of beta-hydroxybutyric acid. This echoes the decline in the abundance of bifidobacteria in the guts of ketogenic diet volunteers and mice.

The researchers then treated the faeces of normal dietary volunteers with beta-hydroxybutyric acid and transplanted it to sterile mice, and found that the effects of beta-hydroxybutyric acid on human intestinal bacteria were consistent with those in mice.

To find out how beta-hydroxybutyric acid affects the abundance of Bifidobacteria. The Turnbaugh team isolated one of the most common Bifidobacterium adolescentis (BD1) from the volunteers’ faeces and treated it directly with beta-hydroxybutyric acid. It was found that beta-hydroxybutyric acid selectively inhibited the growth of Bifidobacteria by means of dose dependence.

The study here becomes clear, because previous studies have found that including B. Bifidobacteria, including perbix (BD1), induces the emergence of large numbers of pro-inflammatory Th17 cells in the intestines.

Immediately after, the Turnbaugh team worked in mice, targeting human gut microbes, to link the relationship between the ketogenic diet, the gut ketones, Bifidobacteria, and the inflammatory Th17 cells.

The ketogenic diet caused the intestines to produce large amounts of beta-hydroxybutyric acid, and an increase in the concentration of beta-hydroxybutyric acid inhibited the growth of Bifidobacteria and ultimately reduced the level of inflammatory Th17 cells.

Cells: The ketogenic diet inhibits the growth of Bifidobacteria in the gut

Anti-inflammatory mechanism map of ketogenic diet

Overall, this study shows that diet-induced host metabolic changes alter the abundance of gut microbes, which in turn affects the immune response. The high-fat diet does not have the same effect as the ketogenic diet, in part because of the lack of ketones produced.

Given that a large number of studies have found microbes throughout the body, the anti-inflammatory mechanisms in the ketogenic diet may also be partly the cause of the ketogenic diet’s improved metabolic disease (control of blood sugar and weight loss).

In addition, in a recent study of ketogenic diet treatment for refractory epilepsy, scientists also found changes in the reduction of Th17 cells in the ketogenic diet group. This, to some extent, supports the universality of the mechanisms discovered by the Turnbaugh team.

“This is a fascinating finding because it shows that the effect of the ketogenic diet on the microbiome is not just the diet itself, but that the diet changes the body’s metabolism and then affects the microbiome and downstream immunity,” Turnbaugh said. “For many people, maintaining a strict, low-carbon water or ketogenic diet can be very difficult, but future research could make treatment more acceptable if future studies find that microbial shifts caused by ketones themselves are enough to have a good impact on health,” he said. “

Expect more good news for Turnbaugh Labs.