Ketogenic diet may reduce seizures by changing microbiome

More than a century ago, physicians at Johns Hopkins University discovered that a strict ketogenic diet—very high in fat, moderate in protein, and very low in carbohydrates—could reduce seizures in a sizable percentage of children with treatment-refractory epilepsy (a problem for a significant number of children with autism). Now, scientists at the University of California at Los Angeles report that the diet may work by altering the gut microbiome in ways that protect against seizures.

Gregory Lum and colleagues collected stool samples from 10 children with refractory epilepsy both before and one month after the children began a clinical ketogenic diet. They then transplanted the children’s microflora into the guts of germ-free mice.

The researchers found that the mice that received the post-treatment microflora were more resistant to induced seizures than the mice that received the pre-treatment microflora. Both the mice and the children also exhibited metabolic changes related to energy production, amino acid metabolism, and oxidation of fatty acids. The metabolic changes persisted in the mice even when the animals ate a standard diet, suggesting, the researchers say, that “the source microbes are maintained under non-ketogenic dietary conditions.” In addition, the mice exhibited changes in the activity of certain genes linked to epilepsy.

While around 30% of children on the clinical ketogenic diet become seizure-free, and around 60% experience a significant reduction in seizures, the diet (which is stricter than most popular “keto” diets) is difficult to follow and has side effects, including nausea, constipation, and fatigue. The researchers hope that by identifying the specific changes caused by the ketogenic diet, it may be possible to make the diet more effective or to come up with other treatments that mimic its beneficial effects.

Citations

“Ketogenic diet therapy for pediatric epilepsy is associated with alterations in the human gut microbiome that confer seizure resistance in mice,” Gregory R. Lum, Sung Min Ha, Christine A. Olson, Montgomery Blencowe, Jorge Paramo, Beck Reyes, Joyce H. Matsumoto, Xia Yang, and Elaine Y. Hsiao, Cell Reports, December 26, 2023 (free online). Address: Gregory Lum, [email protected], or Elaine Hsiao, [email protected].

—and—

“The keto diet protects against epileptic seizures, and scientists are uncovering why,” news release, Kelsie Sandoval, University of California, Los Angeles, December 18, 2023.