Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Epilepsia. 2023 Aug;64(8):e177-e183. doi: 10.1111/epi.17688. Epub 2023 Jun 29.
We have shown previously that the ketogenic diet (KD) is effective in reducing 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 and 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 anti-epileptic effect of the 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 correlated inversely with mitochondrial bioenergetic function and a set of gut microbes, including Streptococcus thermophilus and Streptococcus azizii. These findings suggest that the anti-epileptic and metabolic benefits of the KD decline rapidly in concert with gut microbial alterations in the ISS model.
我们之前已经证明，生酮饮食（KD）在减少与婴儿痉挛综合征（ISS）相关的癫痫发作方面是有效的，并且这种益处与肠道微生物群的改变有关。然而，在切换到正常饮食后，KD 的疗效是否仍然存在仍不清楚。我们采用 ISS 的新生大鼠模型来检验这样一个假设，即在切换到正常饮食后，KD 的影响会减弱。在癫痫发作诱导后，将新生大鼠分为两组：连续 KD 喂养 6 天；一组 KD 喂养 3 天，然后正常饮食 3 天。痉挛频率、海马线粒体生物能学和粪便微生物群被评估为主要指标。我们发现 KD 的抗癫痫作用是可逆的，这可以从从 KD 切换到正常饮食的大鼠痉挛频率增加得到证明。痉挛频率与线粒体生物能学功能和一组肠道微生物呈负相关，包括嗜热链球菌和阿兹兹链球菌。这些发现表明，KD 的抗癫痫和代谢益处与 ISS 模型中肠道微生物的改变一起迅速下降。
