Keys to understanding how the ketogenic diet became a decisive therapy for Refractory Epilepsy

The ketogenic diet, High in fat and low in carbohydrates, it is more than just a fad tactic for weight loss. It is also known to help check the seizures in children with epilepsyparticularly those who do not respond to first-line antiseizure medications.

According to the study by the University of California (UCLA), published in the specialized journal Cell Reports, the changes that the diet causes in the gut microbiome human, where billions of bacteria and other microorganisms live in the digestive tract, can confer Protection against seizures in mice.

Understanding how food intake alters microbiome function could help in the development of new therapeutic approaches that incorporate these beneficial changes and at the same time avoid certain drawbacks of the diet.

The ketogenic option is not recommended as a primary anticonvulsant option because patients are often reluctant to make drastic changes to their food intake or have trouble following the diet due to its strict requirements and possible side effects such as nausea, constipation, and fatigue.

Hoping to find new ways to more effectively treat seizures in about a third of people with refractory epilepsy (who do not respond to existing antiseizure medications), we sought to understand the Underlying molecular mechanisms behind human gut microbiome alteration caused by diet.

Previous research carried out by the laboratory of the same University had discovered that, in a mouse model bred to mimic epilepsy, rodents fed a ketogenic diet had significantly fewer seizures than those on a standard diet.

To take the research a step further, we studied how the gut microbiome is beneficially altered in children with epilepsy who start ketogenic diet therapy. To that end, Fecal samples from pediatric epilepsy patients on the diet were transplanted into mice to evaluate whether the gut microbiota associated with it would protect the rodents against seizures.

Fecal samples were collected in collaboration with the UCLA Ketogenic Diet Therapy Program from 10 pediatric epilepsy patients who did not respond to antiseizure medications and were subsequently treated with a ketogenic diet. They were taken both before starting the diet and after a month of it.

Mice receiving fecal transplants from patients harvested after a month of diet were found to be more resistant to seizures than those receiving fecal transplants from pre-ketogenic intake.

Importantly, it was also found that in pediatric patients, the ketogenic diet altered key functions of the gut microbiome related to fatty acid oxidation and amino acid metabolism, and that These modifications were preserved when the fecal matter was transplanted into the mice.

While more research is needed, this is a result that holds promise toward finding new microbiome-based therapies for pediatric epilepsy patients who do not respond to standard anti-seizure medications. Reducing the functions of microbes that are beneficial in protecting against seizures can potentially lead to new ways to improve the effectiveness of the ketogenic diet or to mimic its beneficial effects.

*Gregory Lum is a researcher at the Department of Integrative Biology and Physiology at the University of California in Los Angeles, United States.