Progress in the study of correlation between gut microbes and epilepsy and its clinical application_Journal of Epilepsy

Authors：

 DENG Yuhong ^1,2,3 , HONG Zhen ⁴ , CAO Dezhi ⁵ , LI Shichuo ⁶

1. Department of Clinical Nutrition , the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China;
2. Institute of Neuroscience and Department of Neurology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China;
3. Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, 510260, China;
4. Department of Neurology, West China Hospital, Sichuan university, Chengdu 610000, China;
5. Department of Neurology, Shenzhen Children’s Hospital, Shenzhen 5180038, China;
6. China Association Against Epilepsy, Beijing 100044, China;

Corresponding author：

DENG Yuhong, Email: 1376708863@qq.com

Keywords：

Epilepsy; Gut microbes; Ketogenic diet; Fecal microbiota transplants; Probiotics

DOI：

10.7507/2096-0247.202301001

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

The correlation between gut microbes and epilepsy is a hot research topic. This review aims to summarize the effects of Ketogenic diet (KD) on gut microbes and the preclinical and clinical progress of the use of Fecal microbiota transplants (FMT) and Probiotics in the intervention of epilepsy to provide clinical reference. Gut microbes mediates the antiepileptic effect of KD. Many studies have found that bactericides decreased in epileptic patients, and KD can increase bactericides abundance, which may be one of its effective mechanisms. Both FMT and probiotics showed antiepileptic effects on epileptic model mice with different pathogenesis, suggesting that gut microbes is an important target for epilepsy treatment. Preliminary clinical studies of small samples suggest that the use of probiotics can effectively treat refractory epilepsy and autoimmune-associated epilepsy, and can improve comorbidities. No serious and long-term side effects of probiotics have been found in epileptic patients. In the future, more high-quality studies are needed to further clarify its efficacy and mechanisms, which could lead to new strategies for epilepsy treatment and refresh our understanding of the causes of epilepsy.

Citation： DENG Yuhong, HONG Zhen, CAO Dezhi, LI Shichuo. Progress in the study of correlation between gut microbes and epilepsy and its clinical application. Journal of Epilepsy, 2023, 9(3): 224-229. doi: 10.7507/2096-0247.202301001 Copy

1.	Cryan JF, O'Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev, 2019, 99(4): 1877-2013.
2.	Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, et al. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin Microbiol Rev, 2022, 35(1): e0033820.
3.	Olson CA, Vuong HE, Yano JM, et al. The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell, 2018, 173(7): 1728-1741.
4.	Citraro R, Lembo F, De Caro C, et al. First evidence of altered microbiota and intestinal damage and their link to absence epilepsy in a genetic animal model, the WAG/Rij rat. Epilepsia, 2021, 62（2）: 529-541.
5.	Medel-Matus JS, Shin D, Dorfman E, et al. Facilitation of kindling epileptogenesis by chronic stress may be mediated by intestinal microbiome. Epilepsia Open, 2018, 3（2）: 290-294.
6.	Bagheri S, Heydari A, Alinaghipour A, et al. Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ-induced chemical kindling. Epilepsy Behav, 2019, 95: 43-50.
7.	Tahmasebi S, Oryan S, Mohajerani HR, et al. Probiotics and Nigella sativa extract supplementation improved behavioral and electrophysiological effects of PTZ-induced chemical kindling in rats. Epilepsy Behav, 2020, 104（PtA）: 106897.
8.	Eor JY, Tan PL, Son YJ, et al. Gut microbiota modulation by both Lactobacillus fermentum MSK 408 and ketogenic diet in a murine model of pentylenetetrazole-induced acute seizure. Epilepsy Res, 2021, 169: 106506.
9.	Xie G, Zhou Q, Qiu CZ, et al. Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy. World J Gastroenterol, 2017, 23（33）: 6164-6171.
10.	Peng A, Qiu X, Lai W, et al. Altered composition of the gut microbiome in patients with drug-resistant epilepsy. Epilepsy Res, 2018, 147: 102-107.
11.	Huang C, Li Y, Feng X, et al. Distinct Gut Microbiota Composition and Functional Category in Children With Cerebral Palsy and Epilepsy. Front Pediatr, 2019, 7: 394.
12.	Safak B, Altunan B, Topçu B, et al. The gut microbiome in epilepsy. Microb Pathog, 2020, 139: 103853.
13.	Lindefeldt M, Eng A, Darban H, et al. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. NPJ Biofilms Microbiomes, 2019, 5（1）: 5.
14.	Lee K, Kim N, Shim JO, et al. Gut Bacterial Dysbiosis in Children with Intractable Epilepsy. J Clin Med, 2020, 10（1）: 5.
15.	龚帅正, 仇君, 吴丽文, 等. 局灶性癫痫患儿治疗前后肠道菌群的变化及意义. 中国当代儿科杂志. 2022, 4（3）: 290-295.
16.	郭晨, 张宇, 刘备, 等. 难治性颞叶癫痫患者的肠道菌群分析. 立体定向和功能性神经外科杂志. 2018, 31（6）: 333-336.
17.	黄晓利, 曾定元, 龙易勤, 等. 癫痫儿童肠道菌群种类及Th17细胞水平的临床研究. 免疫学杂志. 2020, 36（1）: 64-68.
18.	牛迪. 癫痫患者肠道菌群与脑脊液代谢组学分析. 硕士电子期刊出版信息: 2021年第03期网络出版时间: 2021-02-16——2021-03-1510.26994/d. cnki. gdlyu. 2020.000453.
19.	Zhang Y, Zhou S, Zhou Y, et al. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Res, 2018, 145: 163-168.
20.	Zhao FM, Cui BT, Zhang T, et al. Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report. World J Gastroenterol, 2017, 23(19): 3565-3568.
21.	Yeom JS, Park JS, Kim YS, etal. Neonatal seizures and white matter injury: Role of rotavirus infection and probiotics. Brain Dev, 2019, 41（1）: 19-28.
22.	Gómez-Eguílaz M, Ramón-Trapero JL, Pérez-Martínez L, et al. The beneficial effect of probiotics as a supplementary treatment in drug-resistant epilepsy: a pilot study. Benef Microbes, 2018, 9（6）: 875-881.
23.	邓宇虹, 林楚慧, 操德智. 脆弱拟杆菌(BF839)辅助治疗难治性癫痫有效性的初步临床研究. 癫痫杂志, 2021, 7(4): 288-295.
24.	林楚慧, 曾婷, 吴倩仪, 等. 脆弱拟杆菌839治疗新诊断“可能的自身免疫相关癫痫”的疗效. 癫痫杂志, 2022, 8(4): 298-304.
25.	Chen Z, Brodie MJ, Liew D, et al. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol, 2018, 75(3): 279-286.
26.	Bowman LM, Holt PG. Selective enhancement of systemic th1 immunity in immunologically immature rats with an orally, administered bacterial extract. Infection & Immunity, 2001, 69(6): 3719-27.
27.	Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA, 2010, 107(27): 12204-12209.
28.	Erturk-Hasdemir D, Kasper DL. Finding a needle in a haystack: Bacteroides fragilis polysaccharide A as the archetypical symbiosis factor. Ann N Y Acad Sci, 2018, 1417(1): 116-129.
29.	林楚慧, 曾婷, 邓宇虹, 等. 脆弱拟杆菌 BF839 治疗寻常型银屑病: 一项单臂、开放初步临床试验. 生物工程学报, 2021: 3828-3835.
30.	Britton J. Autoimmune epilepsy. Handb Clin Neurol, 2016, 133: 219-45.
31.	Toledano M, Britton JW, McKeon A, et al. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology, 2014, 82(18): 1578-1586.
32.	Steriade C, Britton J, Dale RC, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmuneassociated epilepsy: Conceptual definitions. Epilepsia, 2020, 61(7): 1341-1351.
33.	Shlobin NA, Sander JW. Learning from the coworbidities of epilepsy. Curr Opin Neurd, 2022, 35(2): 175-180.
34.	林楚慧, 曾婷, 林键泓, 等. 脆弱拟杆菌BF839可改善Fmr1KO小鼠的学习记忆能力及社交新奇偏好能力. 中华神经医学杂志. 2022, 21（4）: 341-34.
35.	Strati F, Cavalieri D, Albanese D, et al. Altered gut microbiota in Rett syndrome. Microbiome, 2016, 4（1）: 41.
36.	Borghi E, Borgo F, Severgnini M, et al. Rett Syndrome: A Focus on Gut Microbiota. Int J Mol Sci, 2017, 18(2): 344.

1. Cryan JF, O'Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev, 2019, 99(4): 1877-2013.
2. Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, et al. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin Microbiol Rev, 2022, 35(1): e0033820.
3. Olson CA, Vuong HE, Yano JM, et al. The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell, 2018, 173(7): 1728-1741.
4. Citraro R, Lembo F, De Caro C, et al. First evidence of altered microbiota and intestinal damage and their link to absence epilepsy in a genetic animal model, the WAG/Rij rat. Epilepsia, 2021, 62（2）: 529-541.
5. Medel-Matus JS, Shin D, Dorfman E, et al. Facilitation of kindling epileptogenesis by chronic stress may be mediated by intestinal microbiome. Epilepsia Open, 2018, 3（2）: 290-294.
6. Bagheri S, Heydari A, Alinaghipour A, et al. Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ-induced chemical kindling. Epilepsy Behav, 2019, 95: 43-50.
7. Tahmasebi S, Oryan S, Mohajerani HR, et al. Probiotics and Nigella sativa extract supplementation improved behavioral and electrophysiological effects of PTZ-induced chemical kindling in rats. Epilepsy Behav, 2020, 104（PtA）: 106897.
8. Eor JY, Tan PL, Son YJ, et al. Gut microbiota modulation by both Lactobacillus fermentum MSK 408 and ketogenic diet in a murine model of pentylenetetrazole-induced acute seizure. Epilepsy Res, 2021, 169: 106506.
9. Xie G, Zhou Q, Qiu CZ, et al. Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy. World J Gastroenterol, 2017, 23（33）: 6164-6171.
10. Peng A, Qiu X, Lai W, et al. Altered composition of the gut microbiome in patients with drug-resistant epilepsy. Epilepsy Res, 2018, 147: 102-107.
11. Huang C, Li Y, Feng X, et al. Distinct Gut Microbiota Composition and Functional Category in Children With Cerebral Palsy and Epilepsy. Front Pediatr, 2019, 7: 394.
12. Safak B, Altunan B, Topçu B, et al. The gut microbiome in epilepsy. Microb Pathog, 2020, 139: 103853.
13. Lindefeldt M, Eng A, Darban H, et al. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. NPJ Biofilms Microbiomes, 2019, 5（1）: 5.
14. Lee K, Kim N, Shim JO, et al. Gut Bacterial Dysbiosis in Children with Intractable Epilepsy. J Clin Med, 2020, 10（1）: 5.
15. 龚帅正, 仇君, 吴丽文, 等. 局灶性癫痫患儿治疗前后肠道菌群的变化及意义. 中国当代儿科杂志. 2022, 4（3）: 290-295.
16. 郭晨, 张宇, 刘备, 等. 难治性颞叶癫痫患者的肠道菌群分析. 立体定向和功能性神经外科杂志. 2018, 31（6）: 333-336.
17. 黄晓利, 曾定元, 龙易勤, 等. 癫痫儿童肠道菌群种类及Th17细胞水平的临床研究. 免疫学杂志. 2020, 36（1）: 64-68.
18. 牛迪. 癫痫患者肠道菌群与脑脊液代谢组学分析. 硕士电子期刊出版信息: 2021年第03期网络出版时间: 2021-02-16——2021-03-1510.26994/d. cnki. gdlyu. 2020.000453.
19. Zhang Y, Zhou S, Zhou Y, et al. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Res, 2018, 145: 163-168.
20. Zhao FM, Cui BT, Zhang T, et al. Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report. World J Gastroenterol, 2017, 23(19): 3565-3568.
21. Yeom JS, Park JS, Kim YS, etal. Neonatal seizures and white matter injury: Role of rotavirus infection and probiotics. Brain Dev, 2019, 41（1）: 19-28.
22. Gómez-Eguílaz M, Ramón-Trapero JL, Pérez-Martínez L, et al. The beneficial effect of probiotics as a supplementary treatment in drug-resistant epilepsy: a pilot study. Benef Microbes, 2018, 9（6）: 875-881.
23. 邓宇虹, 林楚慧, 操德智. 脆弱拟杆菌(BF839)辅助治疗难治性癫痫有效性的初步临床研究. 癫痫杂志, 2021, 7(4): 288-295.
24. 林楚慧, 曾婷, 吴倩仪, 等. 脆弱拟杆菌839治疗新诊断“可能的自身免疫相关癫痫”的疗效. 癫痫杂志, 2022, 8(4): 298-304.
25. Chen Z, Brodie MJ, Liew D, et al. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol, 2018, 75(3): 279-286.
26. Bowman LM, Holt PG. Selective enhancement of systemic th1 immunity in immunologically immature rats with an orally, administered bacterial extract. Infection & Immunity, 2001, 69(6): 3719-27.
27. Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA, 2010, 107(27): 12204-12209.
28. Erturk-Hasdemir D, Kasper DL. Finding a needle in a haystack: Bacteroides fragilis polysaccharide A as the archetypical symbiosis factor. Ann N Y Acad Sci, 2018, 1417(1): 116-129.
29. 林楚慧, 曾婷, 邓宇虹, 等. 脆弱拟杆菌 BF839 治疗寻常型银屑病: 一项单臂、开放初步临床试验. 生物工程学报, 2021: 3828-3835.
30. Britton J. Autoimmune epilepsy. Handb Clin Neurol, 2016, 133: 219-45.
31. Toledano M, Britton JW, McKeon A, et al. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology, 2014, 82(18): 1578-1586.
32. Steriade C, Britton J, Dale RC, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmuneassociated epilepsy: Conceptual definitions. Epilepsia, 2020, 61(7): 1341-1351.
33. Shlobin NA, Sander JW. Learning from the coworbidities of epilepsy. Curr Opin Neurd, 2022, 35(2): 175-180.
34. 林楚慧, 曾婷, 林键泓, 等. 脆弱拟杆菌BF839可改善Fmr1KO小鼠的学习记忆能力及社交新奇偏好能力. 中华神经医学杂志. 2022, 21（4）: 341-34.
35. Strati F, Cavalieri D, Albanese D, et al. Altered gut microbiota in Rett syndrome. Microbiome, 2016, 4（1）: 41.
36. Borghi E, Borgo F, Severgnini M, et al. Rett Syndrome: A Focus on Gut Microbiota. Int J Mol Sci, 2017, 18(2): 344.

Previous Article
Research progress of perampanel in the treatment of childhood epilepsy
Next Article
Research progress of executive function in temporal lobe epilepsy

Journal of Epilepsy

Progress in the study of correlation between gut microbes and epilepsy and its clinical application

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content