Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 18 2 2026 04 26 197 203 Ali Abbaskhanian Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran Mohammad Sadegh Rezai Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran Kobra Sheidaee Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran Reza Valadan Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Molecular and Cell Biology Research Center (MCBRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Masood Mohammadi Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran Mona Moradi Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran Golnar Rahimzadeh Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran 2025 11 08 2026 03 31 Background and Objectives: Epilepsy is one of the most common neurological disorders; despite advances in antiepileptic 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 reduction 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. https://ijm.tums.ac.ir/index.php/ijm/article/view/5917 https://ijm.tums.ac.ir/index.php/ijm/article/download/5917/1877