Inflammation, Ketones and the Microbiome

Last week, an interesting biome story came out about research out of the University of California, San Francisco, in which scientists looked at the specific microbiome effects of a ketogenic diet.[i]  As many of you may know, this diet – very low in carbohydrates and proteins in comparison to fats – has been used for over a hundred years to treat childhood epilepsy.  In recent years, it has also become popular for weight loss, with many people believing in its health benefits.  Although its use in the non-seizure population for dieting is still controversial, that it does have significant effects upon health is inarguable.  (I spent a lot of time these past few weeks reading about its use in treating cancer, for example.)

How it works:  when faced with a lack of carbohydrates, which your body ordinarily breaks down into the glucose used to feed every cell of your body, your liver will instead create ketone bodies from fat, which can be used as fuel instead.  It turns out that ketones have a pretty dramatic effect upon the composition of the bacterial microbiome, and are ultimately highly anti-inflammatory and a potential way of treating autoimmune disorders of the gut, like Crohn’s or ulcerative colitis.  (I would imagine, it might be used someday to treat other autoimmune diseases as well.)

In this study, 17 overweight or obese men (without diabetes) spent 2 months as inpatients in a metabolic ward, where diet and exercise were carefully controlled.  For the first 4 weeks of the study, the men were fed either a standard diet (50% carbs, 15% protein, 35% fat) or a ketogenic diet (5% carbs, 15% protein, 80% fat).  After 4 weeks, the two groups switched.  Their microbiomes were analyzed from stool samples:  “Actinobacteria, Bacteroidetes, and Firmicutes in participants’ guts, including significant changes in 19 different bacterial genera. The researchers focused in on a particular bacterial genus—the common probiotic Bifidobacteria—which showed the greatest decrease on the ketogenic diet.”[ii]  The paper itself states:  “Our data support the contribution of select gut bacterial changes, specifically Bifidobacterium, in modulating the intestinal Th17 cell population, consistent with previous work that showed that Bifidobacterium robustly induced intestinal Th17 cells.”

The scientists then took the microbiomes of those on the ketogenic diet and introduced them to mice.  They discovered that this altered microbiome reduced the number of  Th17 immune cells, which are well known to be involved in autoimmune inflammation.  (Remember that inflammation is not bad!  It’s necessary to fight pathogens.  It’s only too MUCH inflammation, or inflammation that doesn’t turn off when no longer necssary, that is problematic.)

In further experiments, the researchers gradually shifted mice’ diets between low-fat, high-fat and low-carb keto diets, which confirmed that a high-fat diet and a keto diet (in spite of this also being high fat) have opposite effects on the gut biome.  That is, it is the presence of carbohydrates or lack thereof in the diet that make the major difference.  Simply reducing carbs in animals on a high-fat diet showed the start of this same shift, correlating with a slow rise in ketones.

The last part of their research is particularly fascinating.  By feeding actual ketones to mice, they found that even those animals eating normal amounts of carbohydrates began to have the beneficial microbial shift seen in a keto diet.  Maintaining a strict ketogenic diet is incredibly difficult for many people; this research suggests though that this may not actually be necessary.  Simply feeding people ketones in the future may turn out to be a really effective way of manipulating the gut bacteria into a less inflammatory composition.

They conclude that their research provides “…evidence that the impact of diet on the gut microbiota is not only translatable from animal models to humans, but also appears to play a causal role in mediating host immune responses to diet. Continued progress in elucidating the mechanistic basis for these observations could help inform more personalized approaches to utilize dietary interventions for the prevention and treatment of human disease.”


[i] Ang, Q. Y., Alexander, M., Newman, J. C., Tian, Y., Cai, J., Upadhyay, V., … Turnbaugh, P. J. (2020). Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. Cell. doi:10.1016/j.cell.2020.04.027


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