In the experiment, which was conducted with mice, researchers found that gut microbes can exacerbate the effects of cognitive impairment because of how they affect the hippocampus, the region of the brain that is critical for memory and learning. They found that the concentration of one group of bacteria called Bilophila increased dramatically in the gut microbiota of mice that were fed a ketogenic diet — high in fat, and low in carbohydrates — and were intermittently deprived of oxygen, creating a condition called hypoxia.
The scientists also found that a ketogenic diet, hypoxia and treatment with a species of Bilophila called Bilophila wadsworthia impaired the hippocampus, leading to reduced cognitive ability in mice.
The researchers gave several mice a ketogenic diet and others a standard diet. Then, all of the mice received reduced levels of oxygen for five consecutive days and then were given four days to recover. Depriving the animals of some oxygen was a way for the scientists to cause cognitive impairment, in order to mimic the cognitive impairment in humans that can be caused by neurological diseases or aging.
Next, the scientists observed their ability to navigate a maze. When trying to find their way out of a maze, mice on the ketogenic diet made an average of 30% more errors than mice given the standard diet. (The range of difference between the two groups was 25% to 75%.)
The researchers also evaluated whether the different diets alone could cause any change in cognitive behavior in mice who had not been deprived of oxygen. In that experiment, there was no appreciable difference in the mice’s ability to find their way out of the maze based on whether they had a ketogenic diet or a standard diet — indicating that the negative impact on cognitive ability only occurred in combination with oxygen deprivation.
[...] Next, the researchers investigated what would happen if they depleted the mice’s microbiota before administering a ketogenic diet and exposing them to hypoxia. Interestingly, mice that had their microbiota depleted first made significantly fewer errors in the maze than mice that were exposed to hypoxia and given a ketogenic diet but had not had changes to their microbiota first.
Christine A. Olson. Alterations in the gut microbiota contribute to cognitive impairment induced by the ketogenic diet and hypoxia, Cell Host & Microbe (DOI: 10.1016/j.chom.2021.07.004)