Project 461426

Epilepsy is the most frequent neurologic problem that occurs in childhood. The disease is characterized by a propensity for an individual to have recurrent and unprovoked epileptic seizures. At present, there is no cure for childhood epilepsy and treatment mainly focuses on controlling seizures. Childhood epilepsy is not a single disease, but many. The sub-type examined in our research is called infantile spasms, a type of epilepsy occurring in young babies. Seizures often occur upon waking and in clusters, and some children can experience hundreds of seizures per day. Due to the rapid rate of development in young children, the consequences of infantile spasms can be devastating to families and risks can include future epilepsy, intellectual and developmental delay or disability, autism and lifelong debilitation. The first line treatment for infantile spasms is drug treatment. However, drug treatment is ineffective in half of all patients and there are significant side effects. In these cases, clinicians often turn to the ketogenic diet, which is a high fat-low carbohydrate diet administered in a formula. While not an ideal or healthy diet, the ketogenic diet is effective in controlling seizures in many cases of childhood epilepsy that do not respond to drug treatment. Our laboratory has shown that the ketogenic diet exerts some of its protective impacts through the gut microbiota, the microbes living in our intestines. Remarkably, we can alter seizures by the gut microbiota alone. Aims of this proposal are to fill current gaps in knowledge regarding the interactions between the ketogenic diet and the gut microbiota. By dissecting the mechanisms by which the diet works, we can target these pathways to develop more effective and safer treatments for this catastrophic condition.