The gut microbiota mediates the anti-seizure effects of the ketogenic diet

By C. A. Olson, H. Vuong, J. Yano, Qingxing Y Liang, David J. Nusbaum, E. Hsiao. Cell, 2018

929 citations recorded by the source corpus.

SUMMARY The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here we show that the gut microbiota is altered by the KD and required for protection against acute electrically-induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ-free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota, and treatment with Akkermansia and Parabacteroides, each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA:glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice.

Subfields: Gastroenterology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/12560dfded09ec4852d934647ae082a0ab281b9f

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Citations in the corpus

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology (2020, background): “Moreover, a relevant contribution of gut microbiota is not only restricted to neuroinflammatory and psychiatric disorders (23–32) but also to brain development (13).”
Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options (2020, background): “…is an intriguing one, with unreplicated early studies suggesting links through the microbiome between the effect of the ketogenic diet and seizure control in epilepsy (Olson et al., 2018), a direct effect of microbiome variation and DRE (Peng et al., 2018), and other links (Lumet al., 2020).”
Gut Microbiome: Profound Implications for Diet and Disease (2019, background): “muciniphila, but KD was only followed for three weeks [67].”
Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing (2020, background): “Apolipoprotein E4 (1-272) fragment is associated with mitochondrial proteins and affects mitochondrial function in neuronal cells.”
Microbiota in health and diseases (2022, background): “Specifically, Akkermansia, Parabacteroides, Sutterella, and Erysipelotrichaceae levels were significantly higher in mice on ketogenic diets.(88) Moreover, mice on ketogenic diets were better protected from acute epileptogenic seizures compared with the control group on a normal diet.”