Evidences for a Role of Gut Microbiota in Pathogenesis and Management of Epilepsy

Abstract

Epilepsy as a chronic neurological disorder is characterized by recurrent, unprovoked epileptic seizures. In about half of the people who suffer from epilepsy, the root cause of the disorder is unknown. In the other cases, different factors can cause the onset of epilepsy. In recent years, the role of gut microbiota has been recognized in many neurological disorders, including epilepsy. These data are based on studies of the gut microbiota-brain axis, a relationship starting by a dysbiosis followed by an alteration of brain functions. Interestingly, epileptic patients may show signs of dysbiosis, therefore the normalization of the gut microbiota may lead to improvement of epilepsy and to greater efficacy of anticonvulsant drugs. In this descriptive review, we analyze the evidences for the role of gut microbiota in epilepsy and hypothesize a mechanism of action of these microorganisms in the pathogenesis and treatment of the disease. Human studies revealed an increased prevalence of Firmicutes in patients with refractory epilepsy. Exposure to various compounds can change microbiota composition, decreasing or exacerbating epileptic seizures. These include antibiotics, epileptic drugs, probiotics and ketogenic diet. Finally, we hypothesize that physical activity may play a role in epilepsy through the modulation of the gut microbiota.

Keywords: epilepsy; gut microbiota; ketogenic diet; physical activity; treatment.

Figure 1

Schematic representation of the interactions between gut microbiota and epilepsy. Intestinal microorganisms can communicate with the brain in various ways, including the production of microbial metabolites, activation of the vagus nerve and modulation of the endocrine and immune response. In conditions of dysbiosis, alterations can occur that favor the onset of epileptic seizures. A reduction in short-chain fatty acids (SCFAs) alters the blood brain barrier, allowing the entry of toxins and inflammatory cytokines. Furthermore, a reduced production of neurotransmitters such as GABA and serotonin in the gut–brain axis can contribute to increase glutamatergic activity in the brain and favor the onset of seizure. External agents (such as antibiotics, probiotics, antiepileptic drugs and ketogenic diet) can modify the gut microbiota in a favorable or opposite direction to epileptic seizures.

Figure 2

Putative role of physical activity in epilepsy. Physical activity can induce or reduce epileptic seizures. In case of intense (or inadequate) physical activity in predisposed subjects, some side effects (such as stress, hyperventilation, fatigue, hypoglycemia, etc.) can alter the gut microbiota towards a condition of dysbiosis and favor epileptic seizures. Adequate and regular physical activity can instead promote gut mobility and create higher microbiota diversity, leading to a reduction or inhibition of seizures.