Gut flora and metabolism are altered in epilepsy and partially restored after ketogenic diets.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the composition of the intestinal microbiota and its association with fecal short chain fatty acids (SCFAs) in children with drug refractory epilepsy (DRE) before and after treatment with a ketogenic diet (KD). METHODS: Herein, we conducted a cross-sectional study of 12 children with DRE and 12 matched healthy controls to compare the changes in fecal microbiomes and SCFAs. Disease cohort also underwent analysis before and after 6 months of KD treatment. RESULTS: A higher microbial alpha diversity and a significant increase in Actinobacteria at the phylum level and Enterococcus, Anaerostipes, Bifidobacterium, Bacteroides, and Blautia at the genus level were observed in the children with DRE. The abundance of the eight epileptic-associated genera was reversed after six months of KD treatment with decreases in Bifidobacterium, Akkermansia, Enterococcaceae and Actinomyces and increases in Subdoligranulum, Dialister, Alloprevotella (p < 0.05). In particular, we identified some taxa that were more prevalent in patients with an inadequate response to KD than in those with an adequate response. Further, a significant correlation was observed between the change in the microbiome genera after KD treatment. The SCFA content in the fecal after 6 months of KD treatment increased and was highly correlated with the gut bacteria. SIGNIFICANCES Dysbiosis of the microbiome could be involved in the pathogenesis of DRE in children, which can be relieved by a KD to a large extent. Gut microbiota and microbial metabolism could contribute to the antiseizure effect of KD.