Eor Ju Young, Son Yoon Ji, Kim Jae-Young, Kang Hoon-Chul, Youn Song Ee, Kim Ji Hun, Kim Sae Hun
College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea; Institute of Life Science and Natural Resources, Korea University, Seoul 136-713, South Korea.
Divison of Pediatric Neurology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Epilepsy Research Institute, Seoul, South Korea.
Epilepsy Res. 2021 Aug;174:106668. doi: 10.1016/j.eplepsyres.2021.106668. Epub 2021 May 13.
We aimed to maximize the efficacy of both ketogenic diet (KD) and other treatments to protect brain from acute seizure.
L. fermentum MSK 408 strain, galactooligosaccharide (GOS), and L. fermentum MSK 408 with GOS were administered with two different diets for 8 weeks. To reveal the relationships among gut microbiota, fecal short-chain fatty acids (SCFAs) and brain related action against pentylenetetrazole (PTZ)-induced kindling, qPCR, NGS, and GC-MS analyses were used.
KD administration significantly reduced PTZ-induced seizure through reducing cell damage in the specific part of the brain; this effect was not interrupted by co-administration of synbiotics. Additionally, the synbiotic-treated normal diet (ND) group showed reduced seizure-related scores. SCFA concentrations of both KDs and ND with synbiotics (NDS) were dramatically reduced compared to those with NDs. Interestingly, NDS group showed independently different SCFAs ratios compared to both ND and KD group, possibly related to a reduction in seizure symptoms compared with that by KD groups. The gut microbiota modulation by KD suggested that the gut microbiota aids the host in generating energy, thus increase the usage of SCFAs such as butyrate and acetate.
The results suggest that KD could reduce PTZ-induced seizures through modulating various factors such as the neuroendocrine system, brain protection, gut microbiota, fecal SCFAs, and gene expression in the gut and brain. Additionally, synbiotic treatment with KD could be a better method to reduce the side effects of KD without interrupting its anti-seizure effect. However, ND with synbiotics seizure reducing effect requires further analysis.
我们旨在使生酮饮食（KD）和其他治疗方法的疗效最大化，以保护大脑免受急性癫痫发作的影响。
将发酵乳杆菌MSK 408菌株、低聚半乳糖（GOS）以及发酵乳杆菌MSK 408与GOS的组合，分别与两种不同的饮食一起给予8周。为了揭示肠道微生物群、粪便短链脂肪酸（SCFAs）与针对戊四氮（PTZ）诱导点燃的脑相关作用之间的关系，采用了qPCR、NGS和GC-MS分析方法。
给予KD通过减少大脑特定部位的细胞损伤，显著降低了PTZ诱导的癫痫发作；这种效果并未因同时给予合生元而受到干扰。此外，接受合生元治疗的正常饮食（ND）组的癫痫发作相关评分有所降低。与单纯ND组相比，KD组和添加合生元的ND组（NDS）的SCFA浓度均显著降低。有趣的是，NDS组与ND组和KD组相比，显示出独立不同的SCFAs比例，这可能与癫痫症状的减轻有关，相比之下KD组的症状减轻程度较小。KD对肠道微生物群的调节表明，肠道微生物群有助于宿主产生能量，从而增加丁酸和乙酸等SCFAs的利用。
结果表明，KD可通过调节神经内分泌系统、脑保护、肠道微生物群、粪便SCFAs以及肠道和大脑中的基因表达等多种因素，来减少PTZ诱导的癫痫发作。此外，KD联合合生元治疗可能是一种更好的方法，可以在不中断其抗癫痫作用的情况下减少KD的副作用。然而，ND联合合生元的抗癫痫作用还需要进一步分析。
