Scientist Finally Know How A Ketogenic Diet Protects Against Epilepsy

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The answer lies within the gut microbiome.

 

A low-carbohydrate, high-fat ketogenic diet can help to treat refractory epilepsy in patients who are non-responsive to anticonvulsive medications.

Studies have shown that more than half of children who switch to the diet see at least a 50% reduction in the number of seizures they experience. Furthermore, a subset (10-15%) becomes seizure-free!

The diet is also being used to manage a growing list of conditions including autism spectrum disorder, Alzheimer’s disease, metabolic syndrome, and cancer.

What scientists haven’t known is why the diet works…

 

Until now.

 

A team at the University of California, Los Angeles (UCLA), has now found that the gut microbiome plays a pivotal role in mediating the protective effects of a ketogenic diet on refractory epilepsy.

Given the growing understanding of the gut-brain axis, (linking the gut microbiome to dietary responses, neuronal activity, and behavior), the researchers hypothesized that the gut microbiome may also play a role in the antiseizure effects of a ketogenic diet.

They tested the ketogenic diet in two mouse epilepsy models, one that undergoes electrically induced seizures and another that spontaneously develops tonic-clonic seizures. 

 

Analyzing the microbiomes of the mice revealed some interesting insights:

  • The gut microbiomes of the mice changed within a few days of starting the ketogenic diet.
  • While the diversity of their gut microbiomes was reduced, populations of others, including Akkermansia muciniphila and Parabacteroides species, were significantly increased.
  • In the electrically stimulated seizures mouse model, the ketogenic diet provided protection against seizures.

 

The scientists found that the microbiome had to be present for the protection to occur; the diet had no beneficial effect on germ-free or antibiotic-treated mice.

However, the protective effects could be restored in antibiotic-treated mice by giving them Akkermansia muciniphila and Parabacteroides orally.

Surprisingly, both bacterial species had to be present for the seizure protection to be restored. If the researchers only gave the antibiotic-treated mice one of the two strains, they saw no significant increase in protection.

If scientists restored the microbiomes of mice on the ketogenic diet to “normal,” the protection went away. This suggests that persistent interactions between the ketogenic diet microbiome, diet, and neuronal activity must be maintained.

The team then carried out the same tests in a mouse model of temporal lobe epilepsy that spontaneously develops tonic-clonic seizures. They again found that Akkermansia muciniphila and Parabacteroides could protect the mice from seizures.

Taken together, the findings show that the gut microbiome mediates the anti-seizure effects of the ketogenic diet in various seizure types.   

Finally, the researchers analyzed the animals' gut, blood, and brains. They found that the ketogenic diet bacteria increased brain levels of GABA (a neurotransmitter that silences neurons) relative to brain levels of glutamate, a neurotransmitter that activates neurons to fire.

The increased GABA/glutamate ratio is what protects the mice against seizures.

The data from the mouse study aligns well with human studies showing that antibiotic treatment increases the risk of seizures in epilepsy patients. These findings now need to be verified in humans.

 

Reference:

Olson, Christine A., et al. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell (2018). DOI: 10.1016/j.cell.2018.04.027