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生酮饮食介导肠道菌群在癫痫中的研究进展
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Abstract:
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。
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.
| [1] | Falco-Walter, J. (2020) Epilepsy—Definition, Classification, Pathophysiology, and Epidemiology. Seminars in Neurolo-gy, 40, 617-623. https://doi.org/10.1055/s-0040-1718719 |
| [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.
https://doi.org/10.1097/CM9.0000000000002526 |
| [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. https://doi.org/10.1016/j.seizure.2016.03.006 |
| [4] | Dahlin, M. and Prast-Nielsen, S. (2019) The Gut Microbiome and Epilepsy. EBioMedicine, 44, 741-746.
https://doi.org/10.1016/j.ebiom.2019.05.024 |
| [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. https://doi.org/10.1155/2019/8373060 |
| [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.
https://doi.org/10.1111/j.0013-9580.2005.48504.x |
| [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. https://doi.org/10.3390/nu12061809 |
| [8] | Koh, S., Dupuis, N. and Auvin, S. (2020) Ke-togenic Diet and Neuro Inflammation. Epilepsy Research, 167, Article 106454. https://doi.org/10.1016/j.eplepsyres.2020.106454 |
| [9] | Donaldson, G.P., Lee, S.M. and Mazmanian, S.K. (2016) Gut Biogeography of the Bacterial Microbiota. Nature Reviews Microbiology, 14, 20-32. https://doi.org/10.1038/nrmicro3552 |
| [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. https://doi.org/10.1002/epi4.12114 |
| [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.
https://doi.org/10.1038/s41598-019-50542-0 |
| [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.
https://doi.org/10.3390/vetsci10040245 |
| [13] | Braakman, H.M.H. and Van Ingen, J. (2018) Can Epilepsy Be Treated by Antibiotics? Journal of Neurology, 265, 1934-1936. https://doi.org/10.1007/s00415-018-8943-3 |
| [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.
https://doi.org/10.1021/acschemneuro.0c00431 |
| [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.
https://doi.org/10.3389/fcimb.2021.749509 |
| [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. https://doi.org/10.3390/jcm10010005 |
| [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. https://doi.org/10.1016/j.micpath.2021.104899 |
| [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. https://doi.org/10.1016/j.eplepsyres.2018.09.013 |
| [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.
https://doi.org/10.1016/j.eplepsyres.2021.106601 |
| [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.
https://doi.org/10.1016/j.chom.2015.03.006 |
| [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. https://doi.org/10.1016/j.cell.2018.04.027 |
| [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.
https://doi.org/10.1016/j.celrep.2023.113521 |
| [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. https://doi.org/10.1172/jci.insight.158521 |
| [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. https://doi.org/10.1111/epi.17688 |
| [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. https://doi.org/10.1016/j.clnesp.2016.11.003 |
| [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.
https://doi.org/10.3748/wjg.v23.i33.6164 |
| [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. https://doi.org/10.1016/j.ebiom.2022.104061 |
| [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.
https://doi.org/10.1038/s41522-018-0073-2 |
| [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. https://doi.org/10.1016/j.eplepsyres.2018.06.015 |
| [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.
https://doi.org/10.3389/fneur.2023.1237255 |
| [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.
https://doi.org/10.3390/ijms23158829 |
| [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. https://doi.org/10.1016/j.cell.2020.04.027 |
| [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.
https://doi.org/10.3389/fnut.2021.613100 |
| [34] | Sourbron, J., Thevissen, K. and Lagae, L. (2021) The Ketogenic Di-et Revisited: Beyond Ketones. Frontiers in Neurology, 12, Article 720073. https://doi.org/10.3389/fneur.2021.720073 |
