生酮饮食介导肠道菌群在癫痫中的研究进展
Advances in Ketogenic Diet-Mediated Gut Flora in Epilepsy
DOI: 10.12677/ACM.2024.143815, PDF,   
作者: 卢 豫：山东大学医学融合与实践中心，山东 济南；济南市中心医院儿科，山东 济南
关键词: 癫痫；生酮饮食；肠道菌群；Epilepsy； Ketogenic Diet； Gut Flora
摘要: 癫痫是最常见的神经系统疾病之一，影响着全球约7000万人。多数癫痫患者经药物治疗病情可得到控制，但约30%的患者对抗癫痫药物(AED)治疗反应差，癫痫发作难以控制，称为耐药性癫痫(DRE)。生酮饮食(KD)是一种含有高脂肪、适量蛋白质和极低碳水化合物的饮食，它作为DRE的替代疗法，安全且有效。基于菌群–肠–脑轴学说在癫痫中的兴起，以及饮食对肠道菌群调控的重要作用，本综述将主要从肠道菌群与癫痫的关系、KD如何调控肠道菌群以及其抗癫痫的关联机制方面总结研究进展。
Abstract: Epilepsy is one of the most common neurological disorders, affecting about 70 million people worldwide. Most patients with epilepsy have their condition controlled by medication, but about 30% respond poorly to antiepileptic drug (AED) therapy and have difficulty controlling their seizures, known as drug-resistant epilepsy (DRE). The ketogenic diet (KD), a diet high in fat, moderate in protein and very low in carbohydrates, is safe and effective as an alternative therapy to DRE. Based on the rise of the flora-gut-brain axis doctrine in epilepsy and the important role of diet in the regu-lation of gut flora, this review will summarize the research progress mainly in terms of the rela-tionship between gut flora and epilepsy, how KD modulates gut flora, and its antiepileptic associa-tion mechanism.
文章引用：卢豫. 生酮饮食介导肠道菌群在癫痫中的研究进展[J]. 临床医学进展, 2024, 14(3): 1097-1103. https://doi.org/10.12677/ACM.2024.143815

参考文献

[1] Falco-Walter, J. (2020) Epilepsy—Definition, Classification, Pathophysiology, and Epidemiology. Seminars in Neurolo-gy, 40, 617-623. [Google Scholar] [CrossRef] [PubMed]
[2] Liu, W., Xu, Y., Lin, Y., et al. (2023) Burden of Epilepsy in China and Its Provinces, 1990 to 2019: Findings from the Global Burden of Disease Study 2019. Chinese Medical Journal, 136, 305-312. [Google Scholar] [CrossRef] 
[3] Ni, F.-F., Li, C.-R., Liao, J.-X., et al. (2016) The Effects of Ketogenic Diet on the Th17/Treg Cells Imbalance in Patients with Intractable Childhood Epilepsy. Seizure, 38, 17-22. [Google Scholar] [CrossRef] [PubMed]
[4] Dahlin, M. and Prast-Nielsen, S. (2019) The Gut Microbiome and Epilepsy. EBioMedicine, 44, 741-746. [Google Scholar] [CrossRef] [PubMed]
[5] Fan, Y., Wang, H., Liu, X., et al. (2019) Crosstalk between the Ketogenic Diet and Epilepsy: From the Perspective of Gut Microbiota. Mediators of Inflammation, 2019, Article ID: 8373060. [Google Scholar] [CrossRef] [PubMed]
[6] Kang, H.C., Kim, Y.J., Kim, D.W. and Kim, H.D. (2005) Ef-ficacy and Safety of the Ketogenic Diet for Intractable Childhood Epilepsy: Korean Multicentric Experience. Epilepsia, 46, 272-279. [Google Scholar] [CrossRef] [PubMed]
[7] Wells, J., Swaminathan, A., Paseka, J. and Hanson, C. (2020) Efficacy and Safety of a Ketogenic Diet in Children and Adolescents with Refractory Epilepsy—A Review. Nu-trients, 12, Article 1809. [Google Scholar] [CrossRef] [PubMed]
[8] Koh, S., Dupuis, N. and Auvin, S. (2020) Ke-togenic Diet and Neuro Inflammation. Epilepsy Research, 167, Article 106454. [Google Scholar] [CrossRef] [PubMed]
[9] Donaldson, G.P., Lee, S.M. and Mazmanian, S.K. (2016) Gut Biogeography of the Bacterial Microbiota. Nature Reviews Microbiology, 14, 20-32. [Google Scholar] [CrossRef] [PubMed]
[10] Medel-Matus, J.-S., Shin, D., Dorfman, E., et al. (2018) Facilitation of Kindling Epileptogenesis by Chronic Stress May Be Mediated by Intestinal Microbiome. Epilepsia Open, 3, 290-294. [Google Scholar] [CrossRef] [PubMed]
[11] De Caro, C., Leo, A., Nesci, V., et al. (2019) Intestinal Inflammation In-creases Convulsant Activity and Reduces Antiepileptic Drug Efficacy in a Mouse Model of Epilepsy. Scientific Reports, 9, Article No. 13983. [Google Scholar] [CrossRef] [PubMed]
[12] García-Belenguer, S., Grasa, L., Palacio, J., et al. (2023) Effect of a Ketogenic Medium Chain Triglyceride-Enriched Diet on the Fecal Microbiota in Canine Idiopathic Epilepsy: A Pilot Study. Veterinary Sciences, 10, Article 245. [Google Scholar] [CrossRef] [PubMed]
[13] Braakman, H.M.H. and Van Ingen, J. (2018) Can Epilepsy Be Treated by Antibiotics? Journal of Neurology, 265, 1934-1936. [Google Scholar] [CrossRef] [PubMed]
[14] Arulsamy, A., Tan, Q.Y., Balasubramaniam, V., et al. (2020) Gut Microbiota and Epilepsy: A Systematic Review on Their Rela-tionship and Possible Therapeutics. ACS Chemical Neuroscience, 11, 3488-3498. [Google Scholar] [CrossRef] [PubMed]
[15] Ceccarani, C., Viganò, I., Ottaviano, E., et al. (2021) Is Gut Microbiota a Key Player in Epilepsy Onset? A Longitudinal Study in Drug-Naive Children. Frontiers in Cellular and In-fection Microbiology, 11, Article 749509. [Google Scholar] [CrossRef] [PubMed]
[16] Lee, K., Kim, N., Shim, J.O. and Kim, G.-H. (2020) Gut Bacterial Dysbiosis in Children with Intractable Epilepsy. Journal of Clinical Medicine, 10, Article 5. [Google Scholar] [CrossRef] [PubMed]
[17] Gong, X., Cai, Q., Liu, X., et al. (2021) Gut Flora and Metabolism Are Altered in Epilepsy and Partially Restored After Ketogenic Diets. Microbial Pathogenesis, 155, Article 104899. [Google Scholar] [CrossRef] [PubMed]
[18] Peng, A., Qiu, X., Lai, W., et al. (2018) Altered Composition of the Gut Microbiome in Patients with Drug-Resistant Epilepsy. Epilepsy Research, 147,102-107. [Google Scholar] [CrossRef] [PubMed]
[19] Lee, H., Lee, S., Lee, D.-H. and Kim, D.W. (2021) A Com-parison of the Gut Microbiota among Adult Patients with Drug-Responsive and Drug-Resistant Epilepsy: An Explorato-ry Study. Epilepsy Research, 172, Article 106601. [Google Scholar] [CrossRef] [PubMed]
[20] Leone, V., Gibbons, S.M., Martinez, K., et al. (2015) Ef-fects of Diurnal Variation of Gut Microbes and High-Fat Feeding on Host Circadian Clock Function and Metabolism. Cell Host & Microbe, 17, 681-689. [Google Scholar] [CrossRef] [PubMed]
[21] Olson, C.A., Vuong, H.E., Yano, J.M., et al. (2018) The Gut Mi-crobiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell, 173, 1728-1741. [Google Scholar] [CrossRef] [PubMed]
[22] Lum, G.R., Ha, S.M., Olson, C.A., et al. (2023) Ketogenic Diet Therapy for Pediatric Epilepsy Is Associated with Alterations in the Human Gut Microbiome that Confer Seizure Re-sistance in Mice. Cell Reports, 42, Article 113521. [Google Scholar] [CrossRef] [PubMed]
[23] Mu, C., Nikpoor, N., Tompkins, T.A., et al. (2022) Targeted Gut Microbiota Manipulation Attenuates Seizures in a Model of Infantile Spasms Syndrome. JCI Insight, 7, e158521. [Google Scholar] [CrossRef] [PubMed]
[24] Shearer, J., Scantlebury, M.H., Rho, J.M., et al. (2023) Intermittent vs Continuous Ketogenic Diet: Impact on Seizures, Gut Microbiota, and Mitochondrial Metabolism. Epilepsia, 64, e177-e183. [Google Scholar] [CrossRef] [PubMed]
[25] Tagliabue, A., Ferraris, C., Uggeri, F., et al. (2017) Short-Term Impact of a Classical Ketogenic Diet on Gut Microbiota in GLUT1 Deficiency Syndrome: A 3-Month Prospective Ob-servational Study. Clinical Nutrition ESPEN, 17, 33-37. [Google Scholar] [CrossRef] [PubMed]
[26] Xie, G., Zhou, Q., Qiu, C.-Z., et al. (2017) Ketogenic Diet Poses A Significant Effect on Imbalanced Gut Microbiota in Infants with Refractory Epilepsy. World Journal of Gastroenterology, 23, 6164-6171. [Google Scholar] [CrossRef] [PubMed]
[27] Dahlin, M., Singleton, S.S., David, J.A., et al. (2022) Higher Levels of Bifidobacteria and Tumor Necrosis Factor in Children with Drug-Resistant Epilepsy Are Associated with Anti-Seizure Response to the Ketogenic Diet. EBioMedicine, 80, Article 104061. [Google Scholar] [CrossRef] [PubMed]
[28] Lindefeldt, M., Eng, A., Darban, H., et al. (2019) The Ketogenic Diet Influences Taxonomic and Functional Composition of the Gut Microbiota in Children with Severe Epilepsy. NPJ Biofilms and Microbiomes, 5, Article No. 5. [Google Scholar] [CrossRef] [PubMed]
[29] Zhang, Y., Zhou, S., Zhou, Y., et al. (2018) Altered Gut Micro-biome Composition in Children with Refractory Epilepsy after Ketogenic Diet. Epilepsy Research, 145, 163-168. [Google Scholar] [CrossRef] [PubMed]
[30] Wang, J., Huang, L., Li, H., et al. (2023) Effects of Keto-genic Diet on the Classification and Functional Composition of Intestinal Flora in Children with Mitochondrial Epilepsy. Frontiers in Neurology, 14, Article 1237255. [Google Scholar] [CrossRef] [PubMed]
[31] Bertuccioli, A., Cardinali, M., Di Pierro, F., et al. (2022) Keto-genic and Low FODMAP Diet in Therapeutic Management of a Young Autistic Patient with Epilepsy and Dysmetabo-lism Poorly Responsive to Therapies: Clinical Response and Effects of Intestinal Microbiota. International Journal of Molecular Sciences, 23, Article 8829. [Google Scholar] [CrossRef] [PubMed]
[32] Ang, Q.Y., Alexander, M., Newman, J.C., et al. (2020) Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. Cell, 181, 1263-1275. [Google Scholar] [CrossRef] [PubMed]
[33] Ferraris, C., Meroni, E., Casiraghi, M.C., et al. (2021) One Month of Classic Therapeutic Ketogenic Diet Decreases Short Chain Fatty Acids Production in Epileptic Patients. Frontiers in Nutrition, 8, Article 613100. [Google Scholar] [CrossRef] [PubMed]
[34] Sourbron, J., Thevissen, K. and Lagae, L. (2021) The Ketogenic Di-et Revisited: Beyond Ketones. Frontiers in Neurology, 12, Article 720073. [Google Scholar] [CrossRef] [PubMed]

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