The research highlights the importance of balancing gut microbiome in managing seizure disorders.
A new study conducted at Karolinska Hospital’s Neuropediatric Department and published in eBioMedicine highlights how the ketogenic, or keto, diet may help reduce seizures in children with drug-resistant epilepsy. This research provides insights into how specific gut bacteria and metabolites could play a role in the anti-seizure effects of the keto diet, focusing on children with epilepsy who have not responded well to standard anti-seizure medications.
Epilepsy is a neurological disorder marked by recurring, unprovoked seizures, caused by abnormal electrical activity in the brain. Other symptoms may include confusion, sensory disturbances, or loss of awareness during seizures, impacting daily life and safety. The severity of seizures can vary widely, from brief lapses in attention and muscle jerks to severe convulsions, including experiencing a tonic-clonic (commonly called a ‘grand mal’) seizure where consciousness is lost. The disorder can develop at any age and may result from genetics, brain injury, infection, or other health conditions, although in many cases, the cause is unknown. People with epilepsy may experience
Current statistics estimate that epilepsy affects over 50 million people globally, and nearly a third of these cases are resistant to treatment, meaning that available anti-seizure medications have not achieved the desired seizure control. Drug-resistance can be particularly dangerous as difficult to treat epilepsy can lead to long-term complications including frequent and uncontrolled seizures, risk of physical harm, memory loss, and overall cognitive decline.
For such cases, especially in children, a keto diet—high in fat, moderate in protein, and low in carbohydrates—has shown possible as a potential alternative treatment, replacing traditional medication. Despite widespread clinical use, the precise mechanisms by which this diet reduces seizure frequency have remained unknown, driving researchers to explore in the current study how the diet influences the body’s microbiome and metabolic pathways.
For their study, the team recruited fourteen children aged 2 to 17 with pharmaco-resistant epilepsy, excluding those who had recently taken antibiotics or probiotics, as these can influence gut bacteria composition. Each child’s diet was customized by a dietitian, incrementally adjusting the ratio of fats to carbohydrates and proteins to reach an optimal balance over several weeks. To gauge the diet’s impact, parents or other caregivers meticulously tracked seizure frequency over a three-month span of time. Children who experienced at least a 50% reduction in seizure frequency were categorized as responders.
Blood samples were collected before the ketogenic diet began as well as at the end of the study period to measure glucose and beta-hydroxybutyrate (β-OHB) levels, with serum and stool samples analyzed for metabolomic and microbiome studies. The results revealed that about half of the participants achieved the targeted reduction in seizure frequency. Metabolomic analyses identified nearly a thousand metabolites, with significant changes in 345 of them, including notable increases in ketone bodies such as 3-hydroxybutyrate and acetoacetate, alongside a decrease in glucose levels. The keto diet appeared to trigger changes in various metabolic pathways, especially those associated with fatty acids.
Interestingly, four plasmalogens (types of lipids associated with cell membrane structure and function) were found to correlate with seizure reduction, as were other metabolites like propionate and thymol sulfate. Conversely, certain diacylglycerols and gamma-glutamyl amino acids were linked to a higher frequency of seizures, suggesting a complex interaction between specific metabolites and seizure activity.
The study also examined shifts in gut microbiota composition, uncovering that four bacterial species from the genus Alistipes were associated with beneficial metabolite production and seizure reduction. On the other hand, certain strains of Escherichia coli and infant-type Bifidobacteria appeared to negatively impact seizure outcomes.
This research represents a step forward in understanding the role of the gut’s microbiome and metabolism in managing epilepsy—especially the drug-resistant type. These initial findings could lead new dietary approaches to improve treatment effectiveness by modifying gut bacteria and metabolic pathways, providing new hope for patients previously considered untreatable.
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Ketogenic diet linked to gut microbes and seizure reduction in epileptic children
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