The Role of Gut Microbiota in Children With Epilepsy Following Ketogenic Diet

Study Overview
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Brief Summary
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The role of human microbiota in neurological disorders via the microbiota-gut-brain axis is recently gaining increased attention due to the knowledge that gut microorganisms are involved in multiple gut and brain functions and metabolic pathways. The hypothesis of the present investigation is that changes of gut microbiota and their metabolic products may be a mechanism of the effectiveness of ketogenic diet in epilepsy. The aim of the present study is to investigate the changes of gut microbiota induced by the ketogenic diet and if certain populations of microorganisms are associated with better seizure control in epileptic children. This is a non-interventional study that will include epileptic children 2-18 years old eligible for ketogenic diet. The gut microbiome of participants will be examined in stools before and three months after the implementation of an olive oil- based ketogenic diet therapy. One of the participants' parents will also be included providing fecal sample for the examination of gut microbiome.

Detailed Description
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The high-fat, adequate protein, low-carbohydrate ketogenic diet (KD) has successfully been used in the treatment of drug resistant epilepsy (DRE) in children since 1920's. The classical KD, with fat to carbohydrate plus protein ratio of 3 or 4:1, as well as less restrictive forms such as Modified Atkins Diet (MAD) or Low Glycemic Index Therapy (LGIT), have been proved to be effective in reducing seizures more than 50% in many patients with low response to more than two antiepileptic drugs (AEDs). Apart from a great number of epileptic syndromes, metabolic conditions like GLUT I-Glucose Transporter I - Deficiency Syndrome and Pyruvate Dehydrogenase Deficiency Syndrome seem to be especially responsive to KD. The role of human microbiota in neurological disorders via the microbiota-gut-brain axis with gut microorganisms getting involved in multiple gut and brain functions and metabolic pathways has recently gained attention .The changes of gut microbiota by the low carbohydrate and low fibre ketogenic diet seem to have an impact on its effectiveness in epilepsy control. Furthermore, metabolic products of gut microorganisms such as SCFAs, apart from producing energy, are implicated in inflammatory pathways and are directly affected by the low fibre - carbohydrate content of the ketogenic diet. The small number of studies so far confirm the role of gut microbiome in seizure control without specifying the exact mechanisms yet. The aim of the present study is to further investigate how gut microbiota and the metabolic products of microorganisms are implicated in the effectiveness of ketogenic diet therapy in epileptic children. The study will include epileptic children 2-18 years old eligible for ketogenic diet according to ILAE. The gut microbiome of participants will be examined at the beginning of the study and three months after following an olive-oil based ketogenic diet therapy. One of the participants' parents will also be included, providing fecal samples for the examination of gut microbiome. A written informed consent will be provided by all the participants or care givers. This is a prospective, non-interventional study which will be held in the Department of Pediatric Neurology, 3d Pediatric Clinic, Attikon Athens University Hospital, in collaboration with the Department of Nutrition and Dietetics, Harokopio University. The study has received approval by the Ethics Committee and the Scientific Board of the Attikon Athens University Hospital.

Official Title
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The Role of Gut Microbiota in Children With Epilepsy Following Ketogenic Diet

Conditions
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Epilepsy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type of epilepsy requiring ketogenic diet (drug-resistant epilepsy or Glut 1 DS or PDHD) eligibility for ketogenic diet according to ILAE no antibiotic intake for at least 2 months before the beginning of the study no probiotics or prebiotics intake for at least 2 weeks before the beginning of the study Exclusion Criteria: - systematic diseases (e.g. inflammatory bowel disease, cancer, autoimmune and cardiometabolic diseases)

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of epileptic seizures frequency | Recording of number of seizures per week/month Recording the ratio of epileptic seizures change e.g. decrease >50%, decrease 50-90%, decrease >90% | 3 months | 
| Changes in electroengephalographic activity | Subjective assessment of neurophysiologist depending on the diagnosis of each patient's epileptic syndrome. Measurement of Spike Wave Index (%) in Electrical Status Epilepticus During Slow-wave Sleep (ESES) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alterations in gut microbiota | alterations in specific gut microbial populations (quantitative real time PCR) | 3 months | 
| Changes in gut microbial metabolites | Short Chain Fatty Acids quantification (gas chromatography) | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketogenic diet, epilepsy, children, gut microbiota