GOODMAN-LUSKIN MICROBIOME CENTER UCLA GOODMAN-LUSKIN MICROBIOME CENTER
High-Fat, Low-Carb Ketogenic Diet Produces Gut Microbiome Changes That May Prevent Seizures
refractory epilepsy who don’t respond to existing anti- seizure medications, Dr. Hsiao’s group sought to understand the underlying molecular mechanisms behind the diet’s alteration of the human gut microbiome. Previous research conducted by Dr. Hsiao’s lab had found that in a mouse model bred to mimic epilepsy, mice fed a ketogenic diet had significantly fewer seizures than mice fed a standard diet. Dr. Lum took that research a step further, studying how the gut microbiome is beneficially altered in children with epilepsy who start ketogenic diet therapy. To that end, he transplanted fecal samples from pediatric epilepsy patients who were on the diet into mice to gauge whether the diet-associated gut microbiota would protect the mice against seizures. The fecal samples were collected in collaboration with UCLA’s Ketogenic Diet Therapy Program from 10 pediatric epilepsy patients who did not respond to anti-seizure medication and were subsequently treated with the ketogenic diet. The samples were taken both before they started the diet and after one month on the diet. The study found that the mice that received fecal transplants from patients collected after a month on the diet were more resistant to seizures than mice that received pre–ketogenic diet fecal transplants. Importantly, the study also found that in the pediatric patients, the ketogenic diet altered key gut microbiome functions related to fatty acid oxidation and amino acid metabolism — and that these changes were preserved when the fecal matter was transplanted into the mice. Dr. Lum notes that more research on these changes is needed, but believes the study holds promise as a step toward finding new microbiome-based therapies for pediatric epilepsy patients who do not respond to standard anti- seizure medications. “Narrowing down the functions of the microbes that are beneficial toward seizure protection can potentially lead to new ways to enhance the efficacy of the ketogenic diet or to mimic its beneficial effects,” he explains.
Elaine Y. Hsiao, PhD
The high-fat, low-carbohydrate ketogenic diet is more than just a trendy weight-loss tactic. It has also been known to help control seizures in children with epilepsy, particularly those who don’t respond to first-line, anti- seizure medications. Now, a study by researchers in the laboratory of Elaine Y. Hsiao, PhD, De Logi Associate Professor of Biological Sciences and director of the Goodman-Luskin Microbiome Center, which is based in the Vatche and Tamar Manoukian Division of Digestive Diseases, provides an explanation. The study, published in the journal Cell Reports , demonstrates that the changes the keto diet causes in the human gut microbiome can confer protection against seizures in mice. This understanding of how the function of the microbiome is altered by the diet could aid in the development of new therapeutic approaches that incorporate these beneficial changes while avoiding certain drawbacks of the diet, says Gregory Lum, PhD, the study’s lead author and a postdoctoral researcher in Dr. Hsiao’s lab. The ketogenic diet is not recommended as a primary anti- seizure option because patients are often averse to drastic changes in their food intake. Many have trouble adhering to the diet’s strict requirements, or tolerating side effects that can include, nausea, constipation, and fatigue. In the hope of finding new ways to more effectively treat seizures in the approximately one-third of people with
“The high-fat, low-carbohydrate ketogenic diet is more than just a trendy weight-loss tactic.”
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uclahealth.org/departments/medicine/gastro
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