Abstract, originally published in Epilepsy Behav.

To answer the question posed in the title of the manuscript, we critically examined the connection between ketogenic diet (KD), gut microbiota (GM), and epilepsy. We conclude that although the evidence for a KD-GM-epilepsy link is fairly robust in rodent epilepsy models, it is very hard to draw meaningful conclusions in humans. The limitations of human studies that have investigated the KD-microbiota-epilepsy relationship include small sample size, a heterogeneous patient population with regard to age and epilepsy type, failure to account for the effect of dietary habits, antiseizure drugs (ASDs) and comedications on GM composition, variability in the KD administered and in the duration of the intervention, and different approaches used in sequencing the microbiome. Although alteration in the GM composition may be a potential indicator of responsiveness/resistance to a KD, we need well-designed randomized case-control and cohort studies involving a large number of a fairly homogenous population of patients with epilepsy adjusted to their habitual dietary habits and region of residence before labeling it as a surrogate marker. Research in this direction may also help us to unravel the mysteries of GM-brain axis not only concerning epilepsy but also in other neurological diseases.

Abstract, published in JAMA Pediatrics

Objectives: The ketogenic diet (KD) has been used successfully to treat children with drug-resistant epilepsy. Data assessing the efficacy of the modified Atkins diet (MAD) and low glycemic index therapy (LGIT) diet, compared with the KD are scarce. The purpose of this study was to determine whether the MAD and LGIT diets, which are often easier to follow, are as effective as the KD among children with drug-resistant epilepsy.

Design, setting, and participants: One hundred seventy children aged between 1 and 15 years who had 4 or more seizures per month, had not responded to 2 or more antiseizure drugs, and had not been treated previously with the KD, MAD, or LGIT diet were enrolled between April 1, 2016 and August 20, 2017 at a tertiary care referral center in India. Children were randomly assigned to receive the KD, MAD, or LGIT diet as additions to ongoing therapy with antiseizure drugs.

Results: One hundred fifty-eight children completed the trial: KD (n = 52), MAD (n = 52), and LGIT diet (n = 54). Analysis showed that, after 24 weeks of the interventions, the proportion of children with greater than 50% seizure reduction was 67.3% with the KD, 51.9% with the MAD, and 59.3% with the LGIT diet. Treatment-related adverse events were similar between the KD and MAD but were significantly less in the LGIT diet.

Conclusions: Data from this study showed that all 3 dietary regimens – KD, MAD, and the LGIT diet – significantly reduce seizure burden. Importantly, the LGIT diet showed a balance between seizure reduction and relatively fewer adverse events compared with the KD and MAD. These potential benefits suggest that the risk-benefit decision regarding the 3 diets needs to be individualized.

Abstract, published in Epilepsy Research

The ketogenic diet has been used to treat intractable epilepsy for many years, yet the mechanism(s) underlying its effectiveness have not been completely explained. Emerging evidence indicates that the ketogenic diet may correct or otherwise alter a gut microbiota whose fecal microbial composition is different from that in healthy individuals.

Recent studies in animal seizure models also reveal an altered gut microbiome, and, interestingly, changes in the composition of the microbiota after ingestion of a ketogenic diet. The effectiveness of the ketogenic diet in these animal models appears to be absolutely dependent on the presence of gut microbiota. Further evidence suggests that effectiveness of the ketogenic diet in controlling seizures may rely on the ability of specific bacterial populations to alter a particular chemical modification of amino acids, the building blocks of proteins, and thus alter their movement into the central nervous system. These studies suggest new directions for research in patients with epilepsy.

The use of ketogenic diet therapies (KDT) in adults has expanded in the last two decades and has been accompanied by a surge of new retrospective as well as prospective studies evaluating its efficacy in adults with epilepsy. In this review article, researchers highlight the recent clinical trials and advances in the use of the ketogenic diet therapy (KDT) in adult patients with epilepsy. The team analyzes the responder rate in regard to the epilepsy syndrome (focal vs generalized) to identify adults who are optimal to consider for KDT.

In addition to its role in treating patients with chronic epilepsy, this study explores the emerging use of the KDT in the critical care setting in adults with refractory and super-refractory status epilepticus as well as other neurologic disorders. Finally, this study  discusses special considerations for the use of KDT in adults with epilepsy including its potential long-term effects on bone and cardiovascular health, and its use in pregnancy.

The human body, though a miraculous machine, is also a sort of mobile terrarium for other living things. In fact, 99% of the genes in your body aren’t yours – they belong to bacteria, viruses, fungi and other microorganisms. These microorganisms live almost everywhere—in the mouth, eyes, nasal passages, genitals and on the skin—but mostly, they’re in your gut.

The gut microbiome includes hundreds of species of bacteria, comprising 100 trillion cells—more than exist in a human body. Yet until very recently, the idea that these microorganisms could influence human health and behavior was soundly rejected.

Over the past decade, however, the gut biome has gained some respect. It’s now recognized as an important part of human health and function, with effects implicated in a variety of conditions, from the obvious (inflammatory bowel disease) to the not-so-obvious (Parkinson’s disease). Neurodevelopmental and mental disorders (such as autism and depression) have been studied most extensively. Neurological disorders, such as stroke and epilepsy, have remained scarcely examined, although interest has been growing.

The gut-brain axis

Given the blood-brain barrier, the idea that bacteria in the gut could influence the brain was even harder to swallow. But an increasing number of studies are finding intimate communication between the gut and brain, as well as complex interplay among the gut microbiome, the brain and the rest of the body.

Given their range of effects on the body and their constant interactions with the nervous system, gut microbiota are now thought to play a role in many neurological disorders. For example, giving antibiotics to mice prone to Alzheimer’s disease — in order to destroy most of the gut bacteria—reduced the number of clumped proteins in the brain that have been linked with dementia. A later study gave young mice antibiotics for only a week; as they grew, their brains showed less evidence of Alzheimer’s.

Do they play a role in epilepsy? Can gut microbiota affect seizure frequency? Can certain populations of bacteria predispose to seizures, and can we harness the power of the microbiome to stop seizures?

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