Characterizing the fecal microbiome in patients on the ketogenic diet for drug resistant epilepsy

Abstract

Background: The ketogenic diet is a dietary therapy with anti-seizure effects. The efficacy of the diet is variable, with initial animal studies suggesting the intestinal microbiome may have a modulating effect. Initial research on the role of the human microbiome in pediatric epilepsy management has been inconclusive.

Methods: In this single-center prospective cohort study, stool samples were collected from 4 patients with drug resistant epilepsy on the ketogenic diet and 9 with drug resistant epilepsy as controls. The samples were analyzed by 16S RNA sequencing.

Results: A trend towards increased alpha diversity was noted among patients on the ketogenic diet compared to the control group. Patients on the ketogenic diet also trended towards a higher relative abundance of Bacteroidaceae, Ruminococcaceae, and Prevotellaceae species. A subset of the control group had a high relative abundance of Bifidobacterium, which may make them a candidate for a trial of the ketogenic diet as a therapeutic option.

Conclusion: These findings add to the growing field of research of how the ketogenic diet modulates the intestinal microbiome in pediatric epilepsy patients. Future emphasis on multi-centre trials, consistent stool collection practices and the establishment of standardized stool biobanking protocols are needed further to validate these novel findings in a pediatric population.

Fig. 1

Flow chart showing patients who consented to participate in the study compared to those who submitted samples for analysis.

Fig. 2

16S Microbiome Sequencing data. Alpha diversity of the cross-sectional cohort of medically refractory patients on the ketogenic diet, or regular diet as demonstrated as a box plot, with each dot representing an individual patient as measured by the inverted Simpson index (A), or Shannon index (B). Relative abundances of bacterial families were represented in a stacked bar graph, with each bar representing an individual patient, and each colour corresponding to a bacterial family (C).