Abstract
BackgroundThe gut microbiota can modulate brain function and behavior and is increasingly recognized as an important factor in mediating the risk of epilepsy and the effects of seizure interventions. Drug therapy is one of the factors that influence the composition of the intestinal microbiota. Q808 is an innovative chemical with strong anticonvulsant activity and low neurotoxicity. However, studies evaluating the effect of Q808 on gut microbial communities are lacking. In this study, we aimed to evaluate the anticonvulsant activity of Q808 on a pentylenetetrazol (PTZ)—induced seizure model and analyze and compare the intestinal microbiota composition of non-PTZ vehicle control group, the PTZ-induced seizure model rats with and without Q808, through 16S rDNA sequencing. Neurotransmitter levels in the hippocampus were quantitatively estimated using HPLC–MS.ResultsThe results suggest that Q808 effectively alleviates seizures in chronic PTZ-kindled model rats. Additionally, based on the analyzed abundance of the gut microbiota, dysbacteriosis of model rats was found to be corrected after Q808 treatment at the phylum level. The unique bacterial taxa (e.g., Lactobacillus) that are associated with acetylcholine production, were significantly increased. Several short-chain fatty acids (SCFAs)-producing bacteria, including Roseburia, Alloprevptella, Prevotellaceae_NK3B31_group, Prevotellaceae_UCG-001, and Prevotella_9, were enriched. In the hippocampus, the contents of acetylcholine increased, whereas the levels of 3-methoxytyramine, glutamine, and 5-hydroxyindole acetic acid (5-HIAA) decreased after Q808 treatment.ConclusionsThis study demonstrates that Q808 can be used to remodel the dysbiosis of the gut microbiome and influence neurotransmitter levels in the hippocampus of PTZ-induced seizure model rats. We hope that these novel findings prompt further research on the interaction between gut microbiota and seizures and the mechanism of Q808.
Highlights
The gut microbiota can modulate brain function and behavior and is increasingly recognized as an important factor in mediating the risk of epilepsy and the effects of seizure interventions
Transferring the gut microbiota of a person suffering from a central nervous system (CNS) disease to animals through stool transplantation can facilitate the transfer of disease symptoms, such as depression [6]
In this study, we provided seminal evidence that Q808 can reconstruct the composition of gut microbiota and increase probiotic levels in the gut
Summary
The gut microbiota can modulate brain function and behavior and is increasingly recognized as an important factor in mediating the risk of epilepsy and the effects of seizure interventions. Depletion of the gut microbiome caused by antibiotic treatment or germ-free mice increases susceptibility to seizures and is associated with alterations in memory, sociability, and cognition [4] These behavioral alterations can be restored by recolonizing the complete microbiota or specific microbes [5]. Other studies suggested a beneficial effect of healthy donor fecal microbiota transplantation (FMT) in disease symptoms and pathogenesis in epilepsy [10]. These animal studies and clinical cases have suggested a potential associations between gut microbiome and epileptic seizures
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