The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet.
Olson CA, Vuong HE, Yano JM, Liang QY, Nusbaum DJ, Hsiao EY
Cell. Jun 2018
COMMENT: This work describes the experiments that support the idea that the previously reported beneficial effects of a ketogenic diet on epileptic seizures are mediated by changes in enzymatic activities from gut microbiome. The metabolic impact in the host, in this case mouse, of the microbial metabolome changes is the increasing of hippocampal GABA/glutamate ratio that appears to confer protection from seizures to 6-Hz mice (mouse model of refractory epilepsy, which involves low-frequency corneal stimulation to induce complex partial seizures similar to human temporal lobe epilepsy) and to reduce the spontaneous seizures in Kcna1-/- mice (mouse model for temporal lobe epilepsy and sudden unexpected death in epilepsy in which the mouse harbors a null mutation in the voltage-gated potassium channel Kv1.1 alpha subunit).
Here, we show that the gut microbiota is altered by the ketogenic diet and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models.
In these two studied mouse models for refractory epilepsy Akkermansia and Parabacteroides appear to be the main responsible for this beneficial effect of the ketogenic diet since antibiotics treated or reared germ free mice are resistant to the seizure protection mediated by ketogenic diet and enrichment of, and gnotobiotic co-colonization of Akkermansia and Parabacteroides are able to restore this seizure protection.
Finally, this is the authors’ opinion about the applicability to human epilepsy treatment:
While the results lend credence to future research examining the gut microbiota in human epilepsy, several additional studies are needed to determine whether microbe-based treatments can be safely and effectively applied for clinical amelioration of seizure severity and incidence.