Keto diet's gut changes may protect against epileptic seizures
A new UCLA study has found how a keto diet induces changes in the gut microbiome that could protect treatment-resistant epileptic children against seizures. The discovery could lead to the development of new therapeutic approaches.
Evidence suggests that the low-carb, high-fat ketogenic (keto) diet can help with weight loss and loss of adipose tissue, lower bad cholesterol, and improve insulin sensitivity. But it’s also been found to be an effective treatment for epileptic children whose seizures aren’t controlled by first-line medicines, a condition called refractory epilepsy.
In the study, researchers examined how the keto diet changes the gut microbiome and its functions and how these molecular changes may protect against seizures.
“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,” said Gregory Lum, lead and corresponding author of the study.
Research into the connection between gut microbiome health and brain health has gained prominence recently. The current study expands on previous UCLA research that found that in a mouse model bred to mimic epilepsy, mice fed a keto diet had significantly fewer seizures than mice fed a standard diet. Now, the researchers looked at how the diet alters the function of the gut microbiome in children with refractory epilepsy.
They collected fecal samples from 10 pediatric epilepsy patients before they commenced eating a keto diet and one month after they started and transplanted the samples into mice. The researchers then tried inducing seizures in the mice using a low-frequency (6 Hz), long-duration (three seconds) stimulus delivered through corneal electrodes (the psychomotor seizure model). They found that mice that received fecal transplants from patients on the keto diet were more resistant to seizures than mice that received pre-keto transplants. On average, the post-keto samples raised seizure thresholds by 22.4% compared to the pre-keto controls.
Importantly, the study also found that in the pediatric patients, the keto diet altered key gut microbiome functions related to fatty acid oxidation and amino acid metabolism. The elevated representation of genes related to these processes suggests that the keto diet shapes the gut microbiome to enrich microbiota that digests fat and synthesizes carbohydrates under fat-rich, carbohydrate-limited conditions. These features were preserved when the pediatric samples were transferred into mice.
Performing transcriptomic profiling of brain tissues from recipient mice, the researchers also observed changes in brain gene expression. Focusing on the hippocampus and frontal cortex based on their relevance to human epilepsy, they found differentially expressed genes relating to RNA processing, cellular stress response, neuronal development, and synaptic activity and signal transmission.
Further research is needed to investigate the mechanisms by which the keto-diet-associated microbiome signals across the gut-brain axis to modify seizure risk and to identify potential microbiome-based interventions that could increase the efficacy of keto-diet treatment.
The study was published in the journal Cell Reports.