Abstract：
A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated.
摘要：
生酮饮食（KD）是一种高脂肪饮食，低碳水化合物，和低蛋白饮食，通过减轻自发性复发性癫痫发作发挥抗癫痫作用，改善学习和记忆障碍，和调节肠道微生物群的组成。然而,肠道微生物组在KD对锂-毛果芸香碱诱导的成年大鼠颞叶癫痫(TLE)的抗癫痫作用中的作用尚不清楚.我们的研究提供的证据表明，KD可有效缓解癫痫发作行为并减少急性期癫痫脑活动，KD治疗可缓解海马神经元损伤并改善TLE引起的认知障碍。我们还观察到,当肠微生物群通过抗生素施用被破坏时,KD的有益效果受到损害。通过从饲喂KD或正常饮食的TLE大鼠收集的粪便样品中的16SrRNA基因测序分析肠道微生物群成分。与正常饮食喂养的TLE大鼠相比，Chao1和ACE指数显示KD喂养的大鼠的物种多样性减少。KD增加了放线菌的水平，细菌和变形杆菌并降低了拟杆菌的水平。有趣的是,放线菌和疣菌的丰度与学习记忆能力呈正相关,变形杆菌的丰度与癫痫发作易感性呈正相关。总之,我们的研究揭示了KD对毛果芸香碱诱导的大鼠癫痫的显著抗癫痫和神经保护作用，主要通过肠道微生物群的调节介导。然而,肠道微生物群是否介导KD的抗癫痫作用仍需要更好地阐明.
