The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet
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This paper examines the role of the gut microbiota in mediating the anti-seizure effects of the ketogenic diet (KD). Finding KD alters the composition of the gut microbiota in mice, increasing Akkermansia muciniphila and Parabacteroides.
The gut microbiota is necessary for the seizure protection provided by the KD. Germ-free mice and antibiotic-treated mice do not show the anti-seizure benefits of the KD. Co-colonization with A. muciniphila and Parabacteroides is sufficient to restore seizure protection in antibiotic-treated mice fed the KD. Transplanting the KD microbiota or treating with A. muciniphila and Parabacteroides confers seizure protection to control diet-fed mice.
The KD and associated microbiota reduce peripheral gamma-glutamylated amino acids and increase hippocampal GABA/glutamate ratios, which correlate with seizure protection. Inhibiting bacterial gamma-glutamyltranspeptidase activity reduces seizures, suggesting a mechanism by which the microbiota impacts neurochemistry and seizures.
https://www.cell.com/cell/pdf/S0092-8674(18)30520-8.pdf
