Ketogenic Diets Alter Gut Microbiome In Humans, Mice

Ketogenic diets have attracted public interest in recent years for their proposed benefits in lowering inflammation and promoting weight loss and heart health.

According to a new UC San Francisco study of a small cohort of volunteer subjects, Low-carb, high-fat ketogenic diets have a dramatic impact on the microbes residing in the human gut.

Human gut is collectively referred to as the microbiome.

ketogenic diets have attracted public interest in recent years for their proposed benefits in lowering inflammation and promoting weight loss and heart health.

Additional studies in mice by the same University of California, San Francisco (UCSF)-led research team demonstrated that ketone bodies, which are a molecular byproduct that gives the ketogenic diet its name, directly change levels of certain types of gut bacteria, which led to reduced levels of intestinal pro-inflammatory immune cells. They suggest the results provide initial evidence for the potential benefits of ketone bodies as a therapy for autoimmune disorders affecting the gut.

“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,” said Peter Turnbaugh, PhD, a UCSF associate professor of microbiology and immunology, member of the UCSF Benioff Center for Microbiome Medicine, and a Chan Zuckerberg Biohub investigator.

“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.”

For their newly reported study, the UCSF-led team partnered with the nonprofit Nutrition Science Initiative to recruit 17 adult overweight or obese nondiabetic men to spend 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% carbohydrates, 15% protein, and 35% fat, or a ketogenic diet comprising 5% carbohydrates, 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.

Follow-up experiments in mice, in which researchers gradually shifted animals’ diets between low-fat, high-fat, and low-carbohydrate 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 researchers observed that that as animals’ diets were shifted from a standard diet towards stricter carbohydrate restriction, there was a shift in microbial populations that correlated with a gradual rise in ketone bodies. “Circulating ketone body levels increased as dietary CHO decreased,” they wrote.

“This was a little surprising to me,” Turnbaugh said. “As someone who is new to the keto field, I had assumed that producing ketone bodies was an all-or-nothing effect once you got to a low enough level of carb intake. But this suggests that you may get some of the effects of ketosis quite quickly.”

The combined results suggest that diet-induced changes in host metabolites alter the gut microbiota, which has downstream effects on immune cells, the team suggested. The impact of a ketogenic diet on the gut microbiota is distinctive from that of an HFD, due in part to the concomitant host production of ketone bodies. “Inhibition of bifidobacterial growth by ketone bodies results in KD-associated decreases in intestinal Th17 cell levels and possibly also adipose tissues,” they concluded.

“Given the links between obesity and chronic low-grade inflammation, decreased levels of pro-inflammatory Th17 cells in both gut and adipose tissues on a KD may be a potential mechanism contributing to the greater efficacy of KD in improving some aspects of metabolic syndrome such as glycemic control and reductions in body fat.”

Unlike other low-carb diets, a true ketogenic diet or keto diet is different. A keto plan centers on fat, which supplies as much as 90% of daily calories. And it’s not the type of diet to try as an experiment.

Because the keto diet has such a high fat requirement, followers must eat fat at each meal. In a daily 2,000-calorie diet, that might look like 165 grams of fat, 40 grams of carbs, and 75 grams of protein. However, the exact ratio depends on your particular needs.

Some healthy unsaturated fats are allowed on the keto diet — like nuts (almonds, walnuts), seeds, avocados, tofu, and olive oil. But saturated fats from oils (palm, coconut), lard, butter, and cocoa butter are encouraged in high amounts.

Protein is part of the keto diet, but it doesn’t typically discriminate between lean protein foods and protein sources high in saturated fat such as beef, pork, and bacon.

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