June 20, 2023

Intermittent Versus Continuous Ketogenic Diet: Impact on Seizures, Gut Microbiota and Mitochondrial Metabolism

Abstract found on PubMed

We have previously shown that the ketogenic diet (KD) is effective in reducing the seizures associated with infantile spasms syndrome (ISS) and that this benefit is related to alterations in the gut microbiota. However, it remains unclear whether the efficacy of the KD persists after switching to a normal diet. Employing a neonatal rat model of ISS, we tested the hypothesis that the impact of the KD would diminish when switched to a normal diet. Following epilepsy induction, neonatal rats were divided into two groups: continuous KD for 6 days; and a group fed with KD for 3 days, then a normal diet for 3 days. Spasms frequency, mitochondrial bioenergetics in the hippocampus, and fecal microbiota were evaluated as major readouts. We found that the antiepileptic effect of KD was reversible, as evidenced by the increased spasms frequency in rats that were switched from the KD to a normal diet. The spasms frequency was inversely correlated with mitochondrial bioenergetic function and a set of gut microbes, including Streptococcus thermophilus and Streptococcus azizii. These findings suggest that the antiepileptic and metabolic benefits of the KD decline rapidly in concert with gut microbial alterations in the ISS model.

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