Intestinal microbiome alterations in pediatric epilepsy: Implications for seizures and therapeutic approaches

The intestinal microbiome plays a pivotal role in maintaining host health through its involvement in gastrointestinal, immune, and central nervous system (CNS) functions. Recent evidence underscores the bidirectional communication between the microbiota, the gut, and the brain and the impact of this axis on neurological diseases, including epilepsy. In pediatric patients, alterations in gut microbiota composition-called intestinal dysbiosis-have been linked to seizure susceptibility. Preclinical models revealed that gut dysbiosis may exacerbate seizures, while microbiome-targeted therapies, including fecal microbiota transplantation, pre/pro-biotics, and ketogenic diets, show promise in reducing seizures. Focusing on clinical and preclinical studies, this review examines the role of the gut microbiota in pediatric epilepsy with the aim of exploring its implications for seizure control and management of epilepsy. We also discuss mechanisms that may underlie mutual gut-brain communication and emerging therapeutic strategies targeting the gut microbiome as a novel approach to improve outcomes in pediatric epilepsy. PLAIN LANGUAGE SUMMARY: Reciprocal communication between the brain and the gut appears to be dysfunctional in pediatric epilepsy. The composition of bacteria in the intestine -known as microbiota- and the gastrointestinal functions are altered in children with drug-resistant epilepsy and animal models of pediatric epilepsies. Microbiota-targeted interventions, such as ketogenic diets, pre-/post-biotics administration, and fecal microbiota transplantation, improve both gastrointestinal dysfunctions and seizures in pediatric epilepsy. These findings suggest that the gut and its microbiota represent potential therapeutic targets for reducing drug-resistant seizures in pediatric epilepsy.