Impact of co-amoxiclav–induced gut microbiota modulation on seizure frequency in children with drug-resistant epilepsy

Abstract

Background and Objectives: Epilepsy is one of the most common neurological disorders; despite advances in antiepilep- tic medications, approximately 15-30% of patients continue to experience drug-resistant seizures. The ketogenic diet has emerged as an effective non-pharmacological treatment for these individuals. Recent studies suggest that changes in gut microbiota may play a role in the diet's ability to reduce seizures. Given this information, our study aimed to investigate the short-term modulation of gut microbiota through antibiotics influences seizure frequency in children with drug-resistant epilepsy.

Materials and Methods: In this open-label clinical trial, 20 children with drug-resistant epilepsy were enrolled in 2020 at a tertiary pediatric clinic in Sari, Iran. Participants received oral co-amoxiclav (amoxicillin-clavulanate) at a dose of 40 mg/ kg per day for five consecutive days. Seizure frequency was monitored before and after the antibiotic intervention. Stool samples were collected at baseline and immediately following treatment, and quantitative real-time PCR was performed to assess all bacterial load as well as the relative abundance of the major gut bacterial groups, Firmicutes and Bacteroides.

Results: The short-term course of co-amoxiclav significantly altered the gut microbiota composition, with a notable reduc- tion in Bacteroidetes and a significant increase in all bacterial gene copies, while the abundance of Firmicutes remained largely unchanged. However, there was no statistically significant change in seizure frequency during the 12-week follow-up period.

Conclusion: Although short-term co-amoxiclav treatment modified the gut microbiota, it did not lead to a meaningful reduction in seizure frequency in children with drug-resistant epilepsy. These findings underscore the complexity of the gut- brain axis and suggest that simple, short-term antibiotic interventions may not be sufficient to influence seizure outcomes. Future studies should involve larger, multicenter cohorts, longer treatment durations, and more comprehensive analyses of microbiota profiles.