Harnessing the Gut Microbiota: New Frontiers in Treating Childhood Epilepsy

Pediatric epilepsy is a chronic neurological disorder, often causing significant physical, neurological and psychological damage. The most common treatment involves anti-seizure medications, but up to one third of children do not respond to them. Increasing evidence implicates the microbiota–gut–brain axis in modulating neuronal signaling, inflammation, and neurodevelopment, suggesting that gut microbiota imbalances may contribute to epileptogenesis and drug resistance. This narrative review gathers studies on pediatric epilepsy and gut microbiota, with two aims: to summarize the current evidence on their relationship, and to explore the potential of microbiota modulation as an adjunctive therapeutic strategy, including current challenges and potential future directions. Relevant English-language articles from PubMed were selected, as well as other articles known to the authors. The gut microbiota of children with epilepsy differs from that of healthy peers, particularly in taxa producing neuromodulatory molecules and pro-inflammatory taxa. The ketogenic diet is the most well-established non-pharmacological intervention. However, it is associated with reduced microbial diversity and depletion of beneficial microbes, raising concerns about the long-term health consequences. Other approaches, including pre/pro/synbiotics, offer a viable way to modulate the microbiota and have demonstrated benefits in various pediatric disorders, although evidence for non-dietary, microbiota-based interventions in pediatric epilepsy remains preliminary and largely preclinical . Alongside fecal microbiota transplantation, innovative strategies, such as defined consortia, live biotherapeutics, and postbiotics, are being developed and hold considerable promise. Together with an increased mechanistic understanding of the microbiota-gut-brain axis in pediatric epilepsy, these strategies could facilitate the implementation of personalized precision adjunct treatments aimed at reducing seizure burden and improving long-term health outcomes.