Epilepsy is the fourth most common neurological disorder affecting over 50 million people worldwide. Recent research indicates that modulation of the gut microbiome can alter the course of the disease in animal models as well as in humans. The gut microbiome is an ecosystem of fungi, viruses, and bacteria that is influenced by an individual’s genetics, diet, and lifestyle. The impact that the gut-brain axis may have on epilepsy is not well understood. Dietary modifications are often used as treatment options for epileptic patients that are unresponsive to other anticonvulsant therapies. In fact, current research indicates that ketogenic diets are associated with a decrease in microbial diversity and diminished seizure activity. It is not known whether this dietary modification works through the gut-brain axis. Zebrafish are a commonly used animal model to study human disease, including epilepsy and gut microbiome mechanisms. The aim of this study is to validate the use of zebrafish to study the interactions between the gut-brain axis and epilepsy, as well as further explore the mechanism by which the microbiome alters the course of the disease. We hypothesize that antibiotic-treated fish will experience diminished seizure responses to Pentylenetetrazol (PTZ) due to a decrease in intestinal bacterial abundance. Zebrafish were treated with broad-spectrum antibiotics to alter the diversity of the microbiome. Fish were then given PTZ to induce a seizure-like state. Seizure activity was recorded and evaluated using EthoVision tracking system and software. Intestinal and brain tissue were harvested for bacterial DNA and RNA respectively. Bacterial abundance was significantly decreased in antibiotic treated fish. Seizure activity was significantly increased in PTZ-treated fish and was surprisingly augmented in antibiotic-treated fish (n= 5, p lt; 0.05). In addition, we observed an increase in glutamate along with a decrease in GABA receptor expression in PTZ-treated fish; these results were reversed in fish treated with both antibiotics and PTZ. Collectively these results indicate that zebrafish are an effective model for studying gut-brain communication involving epilepsy and modulating the gut microbiome may influence seizure activity in PTZ-treated fish.
Support or Funding Information
Lumen fellowship and Honors program, Elon University
