The microbiome–gut–brain axis in epilepsy: pharmacotherapeutic target from bench evidence for potential bedside applications

Abstract The gut–brain axis augments the bidirectional communication between the gut and brain and modulates gut homeostasis and the central nervous system through the hypothalamic–pituitary–adrenal axis, enteroendocrine system, neuroendocrine system, inflammatory and immune pathways. Preclinical and clinical reports showed that gut dysbiosis might play a major regulatory role in neurological diseases such as epilepsy, Parkinson's, multiple sclerosis, and Alzheimer's disease. Epilepsy is a chronic neurological disease that causes recurrent and unprovoked seizures, and numerous risk factors are implicated in developing epilepsy. Advanced consideration of the gut–microbiota–brain axis can reduce ambiguity about epilepsy pathology, antiepileptic drugs, and effective therapeutic targets. Gut microbiota sequencing analysis reported that the level of Proteobacteria , Verrucomicrobia , Fusobacteria, and Firmicutes was increased and the level of Actinobacteria and Bacteroidetes was decreased in epilepsy patients. Clinical and preclinical studies also indicated that probiotics, ketogenic diet, faecal microbiota transplantation, and antibiotics can improve gut dysbiosis and alleviate seizure by enhancing the abundance of healthy biota. This study aims to give an overview of the connection between gut microbiota, and epilepsy, how gut microbiome changes may cause epilepsy, and whether gut microbiome restoration could be used as a treatment for epilepsy.