Research Progress of probiotics in the treatment of Epilepsy_Journal of Epilepsy

Authors：

YUAN Haili ¹ , HE Yongqiao ¹ , DENG Yongyi ¹ ,  MU Jie ²

1. Department of Neurology, People's Hospital of Ganzi Tibetan Autonomous Prefecture, Kangding 626000, China;
2. Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

MU Jie, Email: mujie2010@foxmail.com

Keywords：

Epilepsy; Intestinal microbiota; Gut-brain axis; Probiotics

DOI：

10.7507/2096-0247.202403001

Video：

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Abstract Full text Figures/Tables Video References Cited by

Epilepsy is a common neurological disorder that affect patients' cognitive function and their mental health, imposing a huge burden on families and society. There are approximately 50 million epilepsy patients worldwide, with a prevalence rate of 4‰~7‰ in China, including about 6 million active epilepsy patients. Although scientists have been devoted to the research and exploration of epilepsy, the causes and pathological mechanisms of epilepsy are still poorly understood. The effectiveness of anti-seizure drugs is limited, and more effective methods is needed. With the deepening of microbiological research, many studies have found significant differences in the composition of the intestinal microbiota of epilepsy patients compared to healthy individuals. Analysis of the intestinal microbiota of epilepsy patients through sequencing has shown significantly lower abundances of Bacteroidetes and Firmicutes compared to the normal population. Many related clinical studies have found that adopting a ketogenic diet, taking probiotics orally, using antibiotics, or fecal microbiota transplantation (FMT) can effectively control epilepsy by normalizing the intestinal microbiota. Various studies suggest a possible connection between the intestinal microbiota and epilepsy, recognizing that the intestinal microbiota can have an impact on the central nervous system. As a result, gut-brain axisis gradually recognized by scientists. Therefore, the role of the intestinal microbiota in epilepsy is gradually being recognized, and recent clinical studies have confirmed that supplementing probiotics can effectively reduce seizure frequency and improve comorbidities, which may become a new method for treating epilepsy.

Citation： YUAN Haili, HE Yongqiao, DENG Yongyi, MU Jie. Research Progress of probiotics in the treatment of Epilepsy. Journal of Epilepsy, 2024, 10(3): 240-248. doi: 10.7507/2096-0247.202403001 Copy

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2. Ding D, Zhou D, Sander JW, et al. Epilepsy in China: major progress in the past two decades. Lancet Neurol, 2021, 20(4): 316-326.
3. Kobow K, Blümcke I. Epigenetics in epilepsy. Neurosci Lett, 2018, 667(3): 11568.
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6. Jennum P, Gyllenborg J, Kjellberg J. The social and economic consequences of epilepsy: a controlled national study. Epilepsia, 2011, 52(5): 949-956.
7. Steriade C, Britton J, Dale RC, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy: conceptual definitions. Epilepsia, 2020, 61(7): 1341-1351.
8. He Z, 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.
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(23): 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(11): 102-107.
11. Şafak B, Altunan B, Topcu B, et al. The gut microbiome in epilepsy. Microb Pathog, 2020, 139: 103853.
12. Holmes M, Flaminio Z, Vardhan M, et al. Cross talk between drug-resistant epilepsy and the gut microbiome. Epilepsia, 2020, 61(11): 2619-2628.
13. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol, 2009, 9(5): 313-23.
14. Kamada N, Seo SU, Chen GY, et al. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol, 2013, 13(5): 321-35.
15. Kundu S, Nayak S, Rakshit D, et al. The microbiome-gut-brain axis in epilepsy: pharmacotherapeutic target from bench evidence for potential bedside applications. Eur J Neurol, 2023, 30(11): 3557-3567.
16. Tamburini S, Shen N, Wu HC, et al. The microbiome in early life: implications for health outcomes. Nat Med, 2016, 22: 713–722.
17. Rinninella E, Raoul P, Cintoni M, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms, 2019, 10,7(1): 14.
18. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J, 2017, 16,474(11): 1823-1836.
19. Khanna S, Tosh PK. A clinician's primer on the role of the microbiome in human health and disease. Mayo Clin Proc, 2014, 89: 107-114.
20. Bäckhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe, 2015, 10,17(6): 852.
21. O'Toole PW, Jeffery IB. Gut microbiota and aging. Science, 2015, 350(6265): 1214-5.
22. Pineiro M, Stanton C. Probiotic bacteria: legislative framework-- requirements to evidence basis. J Nutr, 2007, 137(Suppl 2): 850-853.
23. 魏长浩. 益生菌及其应用研究进展. 乳品科学与技术, 2018, 41(1): 26-32.
24. Saad N, Delattre, C, Urdaci, M, et al. An overview of the last advances in probiotic and prebiotic field. Lebensm-wiss Technol, 2013, 50(1): 1-16.
25. Eor JY, Son YJ, Kim JY, et al. Neuroprotective effect of both synbiotics and ketogenic diet in a pentylenetetrazol-induced acute seizure murine model. Epilepsy Res, 2021, 17(4): 106668.
26. Sochocka M, Donskow-Łysoniewska K, Diniz BS, et al. The gut microbiome alterations and inflammation-driven pathogenesis of Alzheimer’s disease-a critical review. Mol Neurobiol, 2019, 56(3): 1841-1851.
27. Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell, 2016, 167(6): 1469-1480.
28. Dahlin M, Prast-Nielsen S. The gut microbiome and epilepsy. EBioMedicine, 2019, 44: 741-746.
29. 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: 1-13.
30. 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.
31. Gong, X, Liu, X, Chen, C, et al. Alteration of gut microbiota in patients with epilepsy and the potential index as a biomarker. Front Microbiol, 2020, 18,11: 517797.
32. Gilbert JA, Blaser MJ, Caporaso JG, et al. Current understanding of the human microbiome. Nat Med, 2018, 24: 392-400.
33. Long-Smith C, O’Riordan KJ, Clarke G, et al. Microbiota-gut-brain axis: new therapeutic oppor tunities. Annu Rev Pharmacol Toxicol, 2020, 60: 477-502.
34. Martin, CR, Osadchiy, V, Kalani, A, et al. The brain-gut-microbiome axis. Cell Mol Gastroenterol Hepatol, 2018, 6(2): 133-148.
35. Fülling C, Dinan TG, Cryan JF. Gut microbe to brain signaling: what happens in vagus. Neuron, 2019, 101: 998-1002.
36. Agirman G, Hsiao EY. Snapshot: The microbiota-gut-brain axis. Cell, 2021, 184(9): 2524-2524.
37. Morais LH, Schreiber HL, Mazmanian SK. The gut microbiota-brain axis in behaviour and brain disorders. Nat Rev Microbiol, 2020, 19(4): 241-255.
38. Ambrosini YM, Borcherding D, Kanthasamy A, et al. The gut-brain axis in neurodegenerative diseases and relevance of the canine model: a review. Front Aging Neurosci, 2019, 11: 130.
39. Abdel-Haq R, Schlachetzki JCM, Glass CK, et al. Microbiome-microglia connections via the gut-brain axis. J Exp Med, 2018, 216(1): 41-59.
40. Kettenmann H, Kirchhoff F, Verkhratsky A. Microglia: new roles for the synaptic stripper. Neuron, 2013, 77(1): 10-18.
41. De Caro C, Iannone LF, Citraro R, et al. Can we ‘seize’ the gut microbiota to treat epilepsy? Neurosci Biobehav Rev, 2019, 107: 750–764.
42. De Caro C, Leo A, Nesci V, et al. Intestinal inflammation increases convulsant activity and reduces antiepileptic drug efficacy in a mouse model of epilepsy. Sci Rep, 2019, 27,9(1): 13983.
43. Wang BH, Hou Q, Lu YQ, et al. Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial pathways in pentylenetetrazol-kindled seizures. Brain Res, 2018, 1,1678: 106-115.
44. Sarkar A, Lehto SM, Harty S, et al. Psychobiotics and the manipulation of bacteria-gut-brain signals. Trends Neurosci, 2016, 39: 763-781.
45. Kennedy PJ, Cryan JF, Dinan TG, et al. Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology, 2017, 112: 399-412.
46. Clarke G, Stilling RM, Kennedy PJ, et al. Minireview: gut microbiota: the neglected endocrine organ. Mol Endocrinol, 2014, 28: 1221-1238.
47. Ding M, Lang Y, Shu H, et al. Microbiota-gut-brain axis and epilepsy: a review on mechanisms and potential therapeutics. Front Immunol, 2021, 11,12: 742449.
48. Sanz P, Garcia-Gimeno MA. Reactive glia inflammatory signaling pathways and epilepsy. Int J Mol Sci, 2020, 8,21(11): 4096.
49. Khakh BS, Sofroniew MV. Diversity of astrocyte functions and phenotypes in neural circuits. Nat Neurosci, 2015, 18(7): 942-52.
50. Ginhoux, F, Lim, S, Hoeffel, G, et al. Origin and differentiation of microglia. Front Cell Neurosci, 2013, 7: 45.
51. Rothhammer V, Borucki DM, Tjon EC, et al. Microglial control of astrocytes in response to microbial metabolites. Nature, 2018, 557(7707): 724-728.
52. Rothhammer V, Mascanfroni ID, Bunse L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med, 2016, 22(6): 586-597.
53. Yang L, Zhou Y, Jia H, et al. Affective immunology: the crosstalk between microglia and astrocytes plays key role? Front Immunol, 2020, 11: 1818.
54. Moradi K, Ashraf-Ganjouei A, Tavolinejad H, et al. The interplay between gut microbiota and autism spectrum disorders: a focus on immunological pathways. Prog Neuropsychopharmacol Biol Psychiatry, 2020, 106: 110091.
55. de Theije CG, Wu J, da Silva, SL, et al. Pathways underlying the gut-to-brain connection in autism spectrum disorders as future targets for disease management. Eur J Pharmacol, 2011, 668(Suppl 1): 70-80.
56. Erny D, Hrabě de Angelis AL, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci, 2015, 18(7): 965-77.
57. Obrenovich MEM. Leaky Gut, Leaky brain? Microorganisms, 2018, 18, 6(4): 107.
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