Mice are more resistant to seizures when treated with gut microbes from children with epilepsy on the low-carbohydrate ketogenic diet. This suggests that the diet’s anti-seizure effect comes from changes to the gut microbiome.
The ketogenic, or keto, diet has been used to treat epilepsy for around a century, but how it does so is unclear. Previously, at the University of California, Los Angeles, and her colleagues found that the diet doesn’t protect against seizures in mice without microbiomes.
“Although we had some work in mice before, it’s really important to test whether what we found relates to the human condition,” she says.
Advertisement
She and her team collected stool samples from 10 children with epilepsy resistant to anti-seizure medications. Each child provided a sample the day before and a month after they began the keto diet. The researchers then freeze-dried the samples and mixed them with a liquid, and fed them to mice on a regular diet, with half the mice receiving pre-keto samples and the other half post-keto samples. All the animals were given antibiotics to deplete their existing gut microbiome so only bacteria in the samples could colonise their guts.
Then, the researchers induced seizures in the mice using electrical stimulation. They found that mice that consumed the post-keto samples needed about 22 per cent more stimulation on average before a seizure occurred compared with mice that ate the pre-keto samples. This indicated that the diet protects against seizures by altering the gut microbiome.
Analysis of stool samples from both the humans and mice showed the keto diet was associated with differences in 20 by-products of digestion called metabolites. These included increases in metabolites related to fat digestion and decreases in kynurenine, which has previously been linked to seizure susceptibility. Genetic analysis of brain tissue samples collected from the mice showed that animals in the post-keto group had altered activity in genes related to seizures and brain inflammation.
“Adherence to the keto diet is a big challenge for people,” says at Johns Hopkins University in Maryland. Understanding how the diet treats epilepsy could help researchers refine treatments so that people don’t have to be as strict with the diet, she says.
However, not all the children in the study benefited from the diet after one month. This could mean they needed to be on the diet for longer, says Hsiao. The other possibility, she says, is that the microbiome may be just one factor that contributes to seizure protection. Genetic differences may block the microbiome effects, she says.
bioRxiv
