Ketogenic diets could alter the gut microbiota, reduce inflammation

A new study, published in Cell, suggests that ketogenic diets could be used as a therapy for autoimmune disorders of the gut.
Table of Contents

• Ketogenic shift
• Opposite effects
• Ketones benefits

What is already known on this topic
Low-carb, high-fat ketogenic diets are publicized for their purported health and weight-loss benefits, but their effects on metabolism and immune function are poorly understood.

What this research adds
By monitoring the diets and exercise levels of 17 people, researchers have found that ketogenic diets altered the gut microbiota in ways that led to reduced levels of inflammatory immune cells in the gut.

The findings suggest that ketogenic diets could be used as a therapy for autoimmune disorders of the gut.

Low-carb, high-fat ketogenic diets, which are publicized for their purported health and weight-loss benefits, have a dramatic impact on the gut microbiota, according to a new study.

The findings, published in Cell, reveal that the changes in gut microbiota composition reduce inflammation, suggesting that ketogenic diets could be used as a therapy for autoimmune disorders of the gut.

Ketogenic diets force the body to use fat molecules, rather than carbohydrates, as its primary energy source, converting fat into fatty acids and molecular byproducts called ketones. However, the effects of these diets on metabolism and immune function are poorly understood.

“Our prior research showed that high-fat diets induce shifts in the gut microbiome that promote metabolic and other diseases in mice, yet ketogenic diets, which are even higher in fat content, have been proposed as a way to prevent or even treat disease,” says senior study author Peter Turnbaugh, a microbiologist and immunologist at the University of California, San Francisco.

To understand this apparent paradox, Turnbaugh and his team closely monitored the diets and exercise levels of 17 overweight or obese men for two months.

Ketogenic shift

For the first four weeks, the study participants ate a standard diet consisting of 50% carbohydrates, 15% protein, and 35% fat. The standard diet was followed by a four-week ketogenic diet consisting of 5% carbohydrates, 15% protein, and 80% fat.

Shifting between standard and ketogenic diets dramatically altered the proportions of gut bacteria such as Actinobacteria, Bacteroidetes, and Firmicutes. Among the microbes whose levels were altered, the gut commensal Bifidobacterium showed the greatest decrease in people on the ketogenic diet.

Opposite effects

To assess whether the shifts in microbial populations impact health, the researchers transferred bacteria from the guts of participants on the ketogenic diet into the guts of mice. After the microbiota transfer, the levels of a type of inflammatory immune cell decreased in the intestine of the rodents.

Follow-up experiments in mice, in which the researchers shifted the animals’ diets from low-fat to high-fat to low-carb ketogenic diets, showed that gut microbe levels driven up by a high-fat diet were driven down by the low-carb ketogenic diet, and vice versa.

These findings show that high-fat and ketogenic diets have opposite effects on the gut microbiota. They also suggest that gut bacteria respond differently as dietary fat increases to levels that promote the production of ketones in the absence of carbs, the authors say.

Ketones benefits

Since a gradual rise in ketone levels was accompanied by a gradual shift in the composition of the gut microbiota, the researchers set out to study whether directly feeding ketone bodies to mice could alter their gut microbiota composition.

Even in rodents who were eating normal amounts of carbohydrates, the presence of ketones was enough to alter the microbiota composition in ways similar to those seen in mice on the ketogenic diet.

“This is a really fascinating finding because it suggests that the effects of ketogenic diets on the microbiome are not just about the diet itself, but how the diet alters the body’s metabolism, which then has downstream effects on the microbiome,” Turnbaugh says. “For many people, maintaining a strict low-carbohydrate or ketogenic diet is extremely challenging, but if future studies find that there are health benefits from the microbial shifts caused by ketone bodies themselves, that could make for a much more palatable therapeutic approach,” he says.