Microbiota–Gut–Brain Axis and Epilepsy: A Review on Mechanisms and Potential Therapeutics

Abstract

The gut–brain axis refers to the bidirectional communication between the gut and brain, and regulates intestinal homeostasis and the central nervous system via neural networks and neuroendocrine, immune, and inflammatory pathways. The development of sequencing technology has evidenced the key regulatory role of the gut microbiota in several neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis. Epilepsy is a complex disease with multiple risk factors that affect more than 50 million people worldwide; nearly 30% of patients with epilepsy cannot be controlled with drugs. Interestingly, patients with inflammatory bowel disease are more susceptible to epilepsy, and a ketogenic diet is an effective treatment for patients with intractable epilepsy. Based on these clinical facts, the role of the microbiome and the gut–brain axis in epilepsy cannot be ignored. In this review, we discuss the relationship between the gut microbiota and epilepsy, summarize the possible pathogenic mechanisms of epilepsy from the perspective of the microbiota gut–brain axis, and discuss novel therapies targeting the gut microbiota. A better understanding of the role of the microbiota in the gut–brain axis, especially the intestinal one, would help investigate the mechanism, diagnosis, prognosis evaluation, and treatment of intractable epilepsy.

The effect of phenobarbital treatment on behavioral comorbidities and on the composition and function of the fecal microbiome in dogs with idiopathic epilepsy

“…MGBA is a bidirectional communication system between the enteric microbiota and the brain, which mainly consists of the central nervous system (CNS), enteric nervous system (ENS), and gastrointestinal microbiota (GIM) ( 7 , 8 ). Communication is exerted through many pathways, namely, neural tracts, immunological, inflammatory, and neuroendocrine pathways ( 9 ). In the last decade, scientific evidence has increased substantially, highlighting the relation between GIM and neuropsychiatric and neurological disorders, namely, epilepsy ( 10 – 12 ).…”

“…SCFAs are fatty acids with fewer than six carbons produced by bacteria, such as Bifidobacterium, Clostridium, and Lactobacillus during polysaccharide fermentation in the colon ( 19 , 20 ). The main SCFAs produced by GIM are acetate, propionate, and butyrate, which are absorbed through the intestine before being circulated to the liver and other organs, namely, the brain ( 9 , 20 ). SCFAs play a major role in maintaining a healthy intestine as they are the main energy source of enterocytes and promote intestinal barrier integrity ( 21 , 22 ).…”

The microbiota‐gut‐brain axis and epilepsy from a multidisciplinary perspective: Clinical evidence and technological solutions for improvement of in vitro preclinical models

“…Research on the relationship between the brain‐gut axis and epilepsy is still at the preliminary stage. Recent studies on murine models have shown a close relation between gut microbiota and the occurrence of multiple types of epilepsy 88 . However, most of the underlying mechanisms are still unknown.…”

“…Recent studies on murine models have shown a close relation between gut microbiota and the occurrence of multiple types of epilepsy. 88 However, most of the underlying mechanisms are still unknown. Progress is being made in developing strategies to investigate the bidirectional communication between the gut and the brain in general with animal models, like germ-free mice, being essential for deepening our understanding of how microbiota alterations shape brain pathophysiology.…”

Neurostimulation as a Method of Treatment and a Preventive Measure in Canine Drug-Resistant Epilepsy: Current State and Future Prospects

“…There might be other processes influencing to lesser extent the onset and progression of epileptogenesis, which might be targeted by brain stimulation. Recently, considerable insight has been gained into the role gastrointestinal microbiota plays in epilepsy ( 181 ). Even though short VNS did not alter gut microbiota composition in mice ( 182 ), repeated TMS of prefrontal cortex influenced rectal function of human volunteers, supposedly also affecting their microbiota ( 183 ).…”