The microbiome as a mediator of focal epilepsy
Prof G Cavalleri
Dr N Delanty
Monday, December 02, 2019
Competition Funded PhD Project (Students Worldwide)
Epilepsy is a group of common brain disorders characterized clinically by the occurrence of recurrent unprovoked seizures. There are many different types of epilepsy, both common and rare. Non-lesional focal epilepsy (NLFE) is a common type, whereby the patient has a focal onset of seizures in the brain, without a demonstrable cause visible on good quality MRI brain imaging. Most cases are unexplained and poorly understood. In addition, many patients with NLFE are do not respond to drug therapies, underpinning the pressing clinical need to further explore and understand this type of epilepsy.
The gut micobiome is defined as the collection of genes of all the microbes present within the gastrointestinal (GI) tract, and studies of the microbiome examine the interaction of all GI flora within the host. There is increasing interest in the gut microbiome as an important determinant of human health and disease, and emerging results from studies of brain disorders such as multiple sclerosis and neuromyelitis optica, supports the hypothesis that perturbations of the microbiome may be of aetiological significance in neurological conditions. Recent work in a mouse model of epilepsy has illustrated how the ketogenic diet (an effective way to control seizures) appears to act through changes in the gut microbiota. Despite this emerging interest in the microbiome and disease, there has been little if any work in humans on its possible role in the development and treatment of epilepsy.
The project will address three principal questions – 1) are changes in gut microbiota correlated with a diagnosis of epilepsy? We will answer this question by comparing the gut microbiota of people with nonlesional focal epilepsy to that of a healthy control population 2) are distinct gut microbioate profiles associated with response to epilepsy treatment? We will answer this question by comparing the gut microbiota of people with treatment-resistant epilepsy to those who respond to treatment. 3) Does the ketogenic diet impact on gut microbiota in people with epilepsy? We will answer this question by comparing the microbiome of people on the ketogenic diet too those who are not on the diet.
This project will be conducted through the SFI FuturNeuro Centre of Excellence and the Epilepsy Program at Beaumont Hospital,the main tertiary referral centre for complex epilepsy in Ireland, and is the national centre for epilepsy surgery. It will facilitate the PhD student to develop cutting edge skills in the generation and analysis of next-generation sequence data, bioinformatics, statistics as well as exposing them to the clinical neurology at Beaumont Hospital.