Ketogenic diet therapy for pediatric epilepsy is associated with alterations in the human gut microbiome that confer seizure resistance in mice

Published: 4 December 2023| Version 1 | DOI: 10.17632/djzyzdbz3z.1
Gregory Lum


The gut microbiome modulates seizure susceptibility and the anti-seizure effects of the ketogenic diet (KD) in animal models, but whether these relationships translate to KD therapies for human epilepsy is unclear. We find that the clinical KD alters gut microbial function in children with refractory epilepsy. Colonizing mice with KD-associated microbes promotes seizure resistance relative to matched pre-treatment controls. Select metagenomic and metabolomic features, including those related to anaplerosis, fatty acid beta-oxidation, and amino acid metabolism, are seen with human KD therapy and preserved upon microbiome transfer to mice. Mice colonized with KD-associated gut microbes exhibit altered hippocampal transcriptomes, including pathways related to ATP synthesis, glutathione metabolism, and oxidative phosphorylation, and linked to susceptibility genes identified in human epilepsy. Our findings reveal key microbial functions that are altered by KD therapies for pediatric epilepsy and linked to microbiome-induced alterations in brain gene expression and seizure protection in mice. Files below contain untargeted metabolomics data from: - human feces, collected within one day before staring the KD (pre-KD) and one month after treatment with the KD (post-KD) - mouse feces and serum, collected from 6-8 week old germ-free Swiss Webester wild-type mice colonized with pre-KD or post-KD human fecal microbiome sample



University of California Los Angeles


Microbiome, Epilepsy, Ketogenic Diet, Gut Microbiome, Intractable Epilepsy