In a new study, researchers found that low-carb, high-fat ketogenic diets have a dramatic impact on the microbes residing in the human gut, collectively referred to as the microbiome.
Keto diets have attracted public interest in recent years for their proposed benefits in lowering inflammation and promoting weight loss and heart health.
Additional research in mice showed that so-called “ketone bodies,” a molecular byproduct that gives the ketogenic diet its name, directly impact the gut microbiome in ways that may ultimately suppress inflammation.
This suggests evidence for the potential benefits of ketone bodies as a therapy for autoimmune disorders affecting the gut.
The research was conducted by a team at UC San Francisco.
In ketogenic diets, carbohydrate consumption is dramatically reduced in order to force the body to alter its metabolism to using fat molecules, rather than carbohydrates, as its primary energy source—producing ketone bodies as a byproduct—a shift that proponents claim has numerous health benefits.
In the study, the team tested 17 overweight or obese men who spent two months as inpatients in a metabolic ward where their diets and exercise levels were carefully monitored and controlled.
For the first four weeks of the study, the participants were given either a “standard” diet consisting of 50% carbs, 15% protein, and 35% fat, or a ketogenic diet comprising 5& carbs, 15& protein, and 80% fat.
After four weeks, the two groups switched diets, to allow the researchers to study how shifting between the two diets altered participants’ microbiomes.
Analysis of microbial DNA found in participants’ stool samples showed that shifting between standard and ketogenic diets dramatically changed the proportions of common gut microbial phyla Actinobacteria, Bacteroidetes, and Firmicutes in participants’ guts, including big changes in 19 different bacterial genera.
The researchers focused on a particular bacterial genus—the common probiotic Bifidobacteria—which showed the greatest decrease in the ketogenic diet.
To better understand how microbial shifts on the ketogenic diet might impact health, the researchers exposed the mouse gut to different components of microbiomes of humans adhering to ketogenic diets and showed that these altered microbial populations specifically reduce the numbers of Th17 immune cells—a type of T cell critical for fighting off infectious disease, but also known to promote inflammation in autoimmune diseases.
Follow-up diet experiments in mice, in which researchers gradually shifted animals’ diets between low-fat, high-fat and low-carb ketogenic diets, confirmed that high-fat and ketogenic diets have opposite effects on the gut microbiome.
These findings suggested that the microbiome responds differently as the level of fat in the animals’ diet increases to levels that promote ketone body production in the absence of carbs.
The findings suggest 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.
The team 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.
The lead author of the study is Peter Turnbaugh, Ph.D., a UCSF associate professor of microbiology and immunology.
The study is published in Cell.
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