Abstract
Simple SummaryThere is evidence that supports the existence of a gut-brain axis system through which bi-directional communication occurs between gut bacteria and the brain. Epilepsy is one of the most common neurological disorders in humans and dogs. The role of microbiota in epilepsy remains unknown but it has been suggested that it is a possible influence of gut bacteria in controlling seizures. The aim of this study was to investigate the changes in gut microbiota from dogs with idiopathic epilepsy and the possible effect of antiepileptic drugs on the modulation of the composition of this microbiota. In comparison with control dogs, drug-naive epileptic individuals showed a significantly reduced abundance of GABA and SCFAs-producing bacteria, as well as bacteria associated with reduced risk for brain disease. Moreover, the use of phenobarbital or imepitoin monotherapy during one month in epileptic dogs did not modify the gut microbiota composition. These results open up the possibility of studying probiotic interventions in epilepsy. Considering the phylogenetic and metabolic similarities in intestinal microbiome between humans and dogs, this study contributes to the understanding of epilepsy both in human and veterinary medicine.Epilepsy is one of the most common neurological disorders in humans and dogs. The structure and composition of gut microbiome associated to this disorder has not yet been analyzed in depth but there is evidence that suggests a possible influence of gut bacteria in controlling seizures. The aim of this study was to investigate the changes in gut microbiota associated to canine idiopathic epilepsy (IE) and the possible influence of antiepileptic drugs (AEDs) on the modulation of this microbiota. Faecal microbiota composition was analyzed using sequencing of bacterial 16S rRNA gene in a group of healthy controls (n = 12) and a group of epileptic dogs both before (n = 10) and after a 30-day single treatment with phenobarbital or imepitoin (n = 9). Epileptic dogs showed significantly reduced abundance of GABA (Pseudomonadales, Pseudomonadaceae, Pseudomonas and Pseudomona_graminis) and SCFAs-producing bacteria (Peptococcaceae, Ruminococcaceae and Anaerotruncus) as well as bacteria associated with reduced risk for brain disease (Prevotellaceae) than control dogs. The administration of AEDs during 30 days did not modify the gut microbiota composition. These results are expected to contribute to the understanding of canine idiopathic epilepsy and open up the possibility of studying new therapeutic approaches for this disorder, including probiotic intervention to restore gut microbiota in epileptic individuals.
Highlights
Evidence of a bi-directional communication between the gastrointestinal tract, containing the gut microbiota, and the central nervous system (CNS) supports the existence of a gut-brain axis system [1].Mutual information exchange between gut bacteria and the brain include neural, blood and immune-endocrine pathways [2]
This study revealed diet- and microbiotadependent regulation of hippocampal GABA and glutamate levels in mice, in accordance with prevailing theories that consider GABA contributes to the antiseizure effects of the ketogenic diet (KD) [23]
In comparison with healthy laboratory beagles, drug-naive epileptic individuals showed a significantly reduced abundance of GABA (Pseudomonadales, Pseudomonadaceae, Pseudomonas and Pseudomona_graminis) and short-chain fatty acids (SCFAs)-producing bacteria (Peptococcaceae, Ruminococcaceae and Anaerotruncus), as well as bacteria associated with reduced risk for brain disease (Prevotellaceae Ga6A1 group)
Summary
Evidence of a bi-directional communication between the gastrointestinal tract, containing the gut microbiota, and the central nervous system (CNS) supports the existence of a gut-brain axis system [1].Mutual information exchange between gut bacteria and the brain include neural, blood and immune-endocrine pathways [2]. Gut microbiota was shown to affect health, behavior and cognitive functions in humans and animals by producing metabolites, hormones and immune factors [3,4] It seems that a stable gut microbiota is essential for normal gut physiology and contributes to appropriate signaling along the brain-gut axis. Gut bacteria produce short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate, which participate in mucus production and intestinal epithelial cell regeneration [9] and contribute to maintaining the integrity of the BBB. These SCFAs are the most abundant produced by anaerobic fermentation of dietary fibers in the intestine. The intestinal mucosal barrier and BBB permeability are affected by several factors, including stress, diet and gut microbiota [6,7]
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