The gut microbiome in drug‐resistant epilepsy

Abstract

Drug‐resistant epileptic patients make up approximately one‐third of the global epilepsy population. The pathophysiology of drug resistance has not been fully elucidated; however, current evidence suggests intestinal dysbiosis, as a possible etiopathogenic factor. Ketogenic diet, whose effect is considered to be mediated by alteration of gut microbiota synthesis, has long been administered in patients with medically refractory seizures, with positive outcomes. In this review, we present data derived from clinical studies regarding alterations of gut microbiome profile in drug‐resistant epileptic patients. We further attempt to describe the mechanisms through which the gut microbiome modification methods (including ketogenic diet, pre‐ or probiotic administration) improve drug‐resistant epilepsy, by reporting findings from preclinical and clinical studies. A comprehensive search of the published literature on the PubMed, Embase, and Web of science databases was performed. Overall, the role of gut microbiome in drug‐resistant epilepsy is an area which shows promise for the development of targeted therapeutic interventions. More research is required to confirm the results from preliminary studies, as well as safety and effectiveness of altering gut bacterial composition, through the above‐mentioned methods.

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

“…Overall, these human studies report alterations in the fecal microbiota of individuals with refractory epilepsy relative to varied non-epileptic controls [ 42 ]. Although these studies show limitations given by the differences among the groups of epileptic patients included and by the methods of investigation used, there seems to be an association between the composition of the gut microbiota and the susceptibility to epileptic activity ( Table 1 ).…”

“…In this review, we highlighted the data on the role of gut microbiota in epilepsy and several methods for modulating the gut microbiota. The aforementioned antibiotics [ 57 ], probiotics [ 42 , 53 , 55 ] and the ketogenic diet [ 81 ].…”

“…There are basically two roads to explore: (1) whether patients resistant to antiepileptic drugs can benefit from additional treatment that acts on the gut microbiota [ 42 , 55 , 98 ]; and (2) explore the possibility of using microbiota gut modulators as a primary treatment for epilepsy [ 99 ], thus eliminating antiepileptic drugs and/or the ketogenic diet, with the benefits that this may entail [ 100 ].…”

The Ketogenic Diet Revisited: Beyond Ketones

“…The latter two bacteria also affect acetate and lactate levels and are involved in regulating the pH and pathogen growth (51). Hence, it seems that specific bacteria can modulate the production of inhibitory neurotransmitters like GABA, possibly by increasing ketogenic gamma-glutamylated amino acids that are substrates for GABA synthesis, which was found to be correlated to the antiseizure effects (52).…”

Recent aspects of ketogenic diet in neurological disorders

“…There is increased interest in identifying the link between the gut and the brain, and the effects of diet on gut microbiota appear to be significant [38][39][40]. In terms of gut microbiota and KD-related anti-seizure properties, dysbiosis can enhance susceptibility for epilepsy and accelerate illness resulting from chronic restraint stress [41].…”