UCLA researchers from the Department of Integrative Biology & Physiology have identified specific components of ketogenic diets that alter the microbiome and improve seizure resistance, providing valuable data to optimize diet treatments for refractory epilepsy.
BACKGROUND: Refractory epilepsy, a disease characterized by uncontrolled seizures, is particularly hard to treat as this condition is resistant to antiepileptic drugs. Recently, the ketogenic diet, which is high in fats and low in carbohydrates, is used to treat refractory epilepsy in children. However, prescribed ketogenic diets vary in macronutrient composition and result in variability in patient response to the diet. Previous research has shown that the microbiome, the collection of all microbes in the human body, plays an important role in the anti-seizure effects of the ketogenic diet. In fact, alterations in the gut microbiome may lead to the observed patient variability in response to the ketogenic diet. However, how this diet mechanistically prevents seizures is yet to be uncovered.
INNOVATION: UCLA researchers have identified specific dietary fibers that correspond to increased seizure resistance in a mouse model. They screened multiple clinical ketogenic diet (KD) infant formulas in a mouse model of epilepsy and found that different formulas were accompanied by differential seizure responses and altered the gut microbiome. Furthermore, researchers identified types of dietary fiber in the KD that caused changes to the microbiome and promoted seizure resistance. Additionally, they identified microbial metagenomic signatures linked to fiber supplementation, allowing them to identify potential biomarkers for seizure resistance. This provides valuable data to manufacture KDs with specific formulations to optimally prevent seizures in refractory epilepsy.
POTENTIAL APPLICATIONS:
- Manipulating gut microbiome to treat refractory epilepsy or drug-resistant epilepsy
- Refining prescribed ketogenic diets to include particular fiber types that lead to seizure resistance
ADVANTAGES:
- Ketogenic diets are already approved and used to treat refractory epilepsy, so refining their composition to be more effective is much more efficient than creating a new drug
- Manipulating the gut microbiome is very clinically feasible, as most drugs are taken orally
- Ketogenic diets are used for other metabolic disorders, so understanding how they impact the microbiome can be valuable to link to other treatments
DEVELOPMENT-TO-DATE: UCLA researchers have identified differential formulations of ketogenic diets in impacting the gut microbiome and inducing seizure resistance in epilepsy.
Related Papers (from the inventors only):
Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., & Hsiao, E. Y. (2018). The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell, 174(2), 497. https://doi.org/10.1016/j.cell.2018.06.051