Role of gut dysbiosis in drug-resistant epilepsy: Pathogenesis and available therapeutic strategies

Over 70 million people worldwide suffer from epilepsy, a persistent brain disorder. Although there are more than 20 antiseizure drugs available for the symptomatic treatment of epilepsy, about one-third of patients with epilepsy experience seizures that show resistance to pharmacotherapy. Since patients with drug-resistant epilepsy are more prone to physical injuries, psychosocial dysfunction, early death, and deteriorated life quality, the development of safer and more effective treatments is a crucial clinical need. The gut-brain axis and microbiome research advances have provided new insights into the pathophysiology of epilepsy, the resistance to anti-seizure medicine, and potential treatment targets. Inflammation, disturbance of the blood-brain barrier, and altered neurotransmitters are key pathways linked to gut dysbiosis. The characterization of microbial species and functional pathways has advanced thanks to metagenomic sequencing and high-throughput analysis. In this review, we elaborate on the gut-mediated molecular pathways involved in drug-resistant epilepsy, the gutmodulatory therapeutic options, and their combination with antiseizure medications for drug-resistant epilepsy.