Research progress on gut microbiota and epilepsy_Journal of Epilepsy

Authors：

QU Xiaoxiao ^1,2 , ZHAO Kexin ^2,3 ,  DI Zhengli ²

1. Xi’an Medical University, Xi'an 710000, Shaanxi, China;
2. Department of Neurology, Xi'an Central Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Xi'an 710000, Shaanxi, China;
3. Yan'an University School of Medicine, Yan'an 716000, Shaanxi, China;

Corresponding?author：

DI Zhengli, Email: dizhengli@163.com

Keywords：

Epilepsy; Gastrointestinal Microbiome; Research progress; Ketogenic Diet

DOI：

10.7507/2096-0247.202605002

Video：

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Abstract Full text Figures/Tables Video References Cited by

Epilepsy is a chronic neurological disorder caused by abnormal neuronal discharges in the brain, affecting a large population worldwide. Approximately one-third of patients develop drug-resistant epilepsy, posing significant challenges in clinical management. Recent evidence highlights the involvement of gut microbiota (gastrointestinal microbiome, GM) in epilepsy pathogenesis and progression through the gut-brain axis. Patients with epilepsy exhibit marked alterations in the composition and function of gut microbiota, which may influence the disease process via immune, neuroendocrine, and metabolic pathways. Interventions targeting the gut microbiota have emerged as a promising therapeutic strategy. This review summarizes recent advances in the field and discusses the potential applications and challenges of microbiota-based interventions, aiming to provide new insights for epilepsy treatment.

Citation： QU Xiaoxiao, ZHAO Kexin, DI Zhengli. Research progress on gut microbiota and epilepsy. Journal of Epilepsy, 2026, 12(4): 337-342. doi: 10.7507/2096-0247.202605002 Copy

1.	Fisher RS, Cross JH, D'Souza C, et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia, 2017, 58(4): 531-542.
2.	Thurman DJ, Beghi E, Begley CE, et al. Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia, 2011, 52(Suppl 7): 2-26.
3.	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.
4.	Asadi-Pooya AA, Brigo F, Lattanzi S, et al. Adult epilepsy. Lancet, 2023, 402(10399): 412-424.
5.	Faysal M, Zehravi M, Sutradhar B, et al. The microbiota-gut-brain connection: A new horizon in neurological and neuropsychiatric disorders. CNS Neurosci Ther, 2025, 31(9): e70593.
6.	Volpedo G, Riva A, Nobili L, et al. Gut-immune-brain interactions during neurodevelopment: from a brain-centric to a multisystem perspective. BMC Med, 2025, 23(1): 263.
7.	Dahlin M, Prast-Nielsen S. The gut microbiome and epilepsy. EBioMedicine, 2019, 44: 741-746.
8.	馬飛, 李致文, 張琴琴. 癲癇與腸道菌群的相互作用及其臨床意義. 神經疾病與精神衛生, 2025, 25(4): 264-269.
9.	曾慶煌, 魏鳳芳, 許金霞, 等. 癲癇患兒腸道菌群失衡狀況及影響因素分析. 中國病原生物學雜志, 2025, 20(4): 411-414,420.
10.	Fang S, Hu N, Zhou C, et al. The comparison of gut microbiota between different types of epilepsy in children. Microb Cell Fact, 2025, 24(1): 64.
11.	Yuwattana R, Suparan K, Kerdphoo S, et al. Altered gut microbiome profiles in epileptic children are associated with spectrum of anti-seizure medication responsiveness. Brain Res, 2025, 1849: 149367.
12.	Riva A, Sahin E, Volpedo G, et al. Identification of an epilepsy-linked gut microbiota signature in a pediatric rat model of acquired epilepsy. Neurobiol Dis, 2024, 194: 106469.
13.	趙瑞, 高嶺, 王有峰, 等. 柴貝止癇湯通過調控mTOR/HIF-1α通路對癲癇大鼠腸道菌群和Th17/Treg細胞免疫平衡的影響. 中國免疫學雜志, 2025, 41(1): 129-135.
14.	黃璐嫣, 董博思, 彭安嬌, 等. 基于小鼠模型探索腸道菌群在癲癇發病機制中的作用. 現代醫學, 2025, 53(4): 629-638.
15.	Mousavi SM, Younesian S, Ejtahed HS. The alteration of gut microbiota composition in patients with epilepsy: a systematic review and meta-analysis. Microbial Pathogenesis, 2025, 199: 107266.
16.	Yang H, Liu W, Gao T, et al. Causal associations between gut microbiota, circulating inflammatory proteins, and epilepsy: a multivariable Mendelian randomization study. Front Immunol, 2024, 15: 1438645.
17.	Zhang X, Yang Z, Guo J, et al. Associations between the gut microbiota, immune cells, and different subtypes of epilepsy: a Mendelian randomization study. Epilepsia Open, 2025, 10(4): 1133-1146.
18.	Kwack DW, Lee S, Lee DH, et al. Changes in gut microbiome can be associated with abrupt seizure exacerbation in epilepsy patients. Clin Neurol Neurosurg, 2024, 246: 108556.
19.	Hong B. Gut flora reflects potential risk factors for cognitive dysfunction in patients with epilepsy. J Health Popul Nutr, 2024, 43(1): 155.
20.	Ilhan ZE, Brochard V, Lapaque N, et al. Exposure to anti-seizure medications impact growth of gut bacterial species and subsequent host response. Neurobiol Dis, 2022, 167: 105664.
21.	Dop C, Kalmutzki MJ, Brochard V, et al. Longitudinal exposure to antiseizure medications shape gut microbial composition, resistome, and metabolome. ISME Commun, 2024, 4(1): ycae123.
22.	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. e13.
23.	Dahlin M, Wheelock CE, Prast-Nielsen S. Association between seizure reduction during ketogenic diet treatment of epilepsy and changes in circulatory metabolites and gut microbiota composition. EBioMedicine, 2024, 109: 105400.
24.	Grill MF, Maganti RK. Neurotoxic effects associated with antibiotic use: management considerations. Br J Clin Pharmacol, 2011, 72(3): 381-93.
25.	Jia Y, Chen H, Zou Q, et al. Gut-brain cholinergic signaling mediates the antiseizure effects of Bacteroides fragilis. Neuron, 2026, 114(6): 1021-1044. e9.
26.	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.
27.	Borowicz-Reutt K, Krawczyk M, Czernia J. Ketogenic diet in the treatment of epilepsy. Nutrients, 2024, 16(9): 1258.
28.	?zcan E, Yu KB, Dinh L, et al. Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice. Nat Commun, 2025, 16(1): 987.
29.	Yu F, Ji JL, Wang Y, et al. Anti-epileptic and gut-protective effects of trioctanoin and the critical role of gut microbiota in a mouse model of epilepsy. Brain Res Bull, 2025, 227: 111401.
30.	Mu C, Kesler M, Chen X, et al. Exogenous ketones exert antiseizure effects and modulate the gut microbiome and mycobiome in a clinically relevant murine model of epilepsy. Epilepsia, 2024, 65(12): 3676-3688.
31.	Shakoor MU, Tareen FK, Rehman Z, et al. Probiotics by modulating gut-brain axis together with brivaracetam mitigate seizure progression, behavioral incongruities, and prevented neurodegeneration in pentylenetetrazole-kindled mice. CNS Neurosci Ther, 2024, 30(11): e70078.
32.	Ali MH, Raza Z, Rehman Z, et al. Probiotics and pregabalin combination prevented ictogenesis, neurobehavioral abnormalities and neurodegeneration in pentylenetetrazole kindling model of epilepsy. Brain Res, 2025, 1855: 149597.
33.	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, 174: 106668.
34.	Matta T, Bishnoi M, Gupta S, et al. GABA-producing Levilactobacillus brevis LAB6 mitigates pentylenetetrazol-induced gut-brain dysregulation in SD rats. J Neurochem, 2025, 169(6): e70141.
35.	岳明, 郜廣冉, 劉俊英. 新型復方益生菌聯合左乙拉西坦治療難治性癲癇患兒的效果及對T淋巴細胞亞群、腸道菌群的影響. 臨床誤診誤治, 2025, 38(5): 42-47.
36.	Shariatmadari F, Motaghi A, Arjmand Shabestari A, et al. The effect of synbiotics in the treatment of drug-resistant epilepsy and the parental burden of caregivers: a single-arm pretest-posttest trial. BMC Pediatr, 2024, 24(1): 666.
37.	吳岳彪, 蔡露良, 林魯飛. 酪酸梭菌輔助治療對癲癇患者腸道菌群分布及腸道黏膜通透性的影響. 中國微生態學雜志, 2024, 36(7): 817-820,827.
38.	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.
39.	Vendrik KEW, Ooijevaar RE, de Jong PRC, et al. Fecal microbiota transplantation in neurological disorders. Front Cell Infect Microbiol, 2020, 10: 98.
40.	Medel-Matus JS, Simpson CA, Ahdoot AI, et al. Modification of post-traumatic epilepsy by fecal microbiota transfer. Epilepsy Behav, 2022, 134: 108860.
41.	Zou S, Li Y, Zou Q, et al. Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility. Front Microbiol, 2024, 15: 1403892.
42.	Watanangura A, Meller S, Farhat N, et al. Behavioral comorbidities treatment by fecal microbiota transplantation in canine epilepsy: a pilot study of a novel therapeutic approach. Front Vet Sci, 2024, 11: 1385469.
43.	Wu Y, Gu D, Li J, et al. Role of the gut microbiota in cefoperazone/sulbactam-induced epilepsy in mice with chronic renal failure. Ren Fail, 2024, 46(2): 2371551.
44.	Zou Q, Zhang Y, Zou S, et al. Ciprofloxacin-induced microbiota dysbiosis triggers seizure susceptibility through the microbiota-gut-brain axis. Front Immunol, 2026, 17: 1670694.
45.	Stokes JM, Davis JH, Mangat CS, et al. Discovery of a small molecule that inhibits bacterial ribosome biogenesis. eLife, 2014, 3: e03574.
46.	Ding M, Lang Y, Shu H, et al. Microbiota-gut-brain axis and epilepsy: a review on mechanisms and potential therapeutics. Front Immunol, 2021, 12: 742449.
47.	Takeno S, Sakai T. Involvement of the intestinal microflora in nitrazepam-induced teratogenicity in rats and its relationship to nitroreduction. Teratology, 1991, 44(2): 209-14.
48.	Sutter R, Rüegg S, Tschudin-Sutter S. Seizures as adverse events of antibiotic drugs: a systematic review. Neurology, 2015, 85(15): 1332-41.
49.	Cannon JP, Lee TA, Clark NM, et al. The risk of seizures among the carbapenems: a meta-analysis. J Antimicrob Chemother, 2014, 69(8): 2043-55.
50.	Jia B, Baek JH, Lee JK, et al. Expanding the β-lactamase family in the human microbiome. Adv Sci (Weinh), 2024, 11(46): e2403563.
51.	Kebede V, Ravizza T, Balosso S, et al. Early treatment with rifaximin during epileptogenesis reverses gut alterations and reduces seizure duration in a mouse model of acquired epilepsy. Brain Behav Immun, 2024, 119: 363-380.

1. Fisher RS, Cross JH, D'Souza C, et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia, 2017, 58(4): 531-542.
2. Thurman DJ, Beghi E, Begley CE, et al. Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia, 2011, 52(Suppl 7): 2-26.
3. 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.
4. Asadi-Pooya AA, Brigo F, Lattanzi S, et al. Adult epilepsy. Lancet, 2023, 402(10399): 412-424.
5. Faysal M, Zehravi M, Sutradhar B, et al. The microbiota-gut-brain connection: A new horizon in neurological and neuropsychiatric disorders. CNS Neurosci Ther, 2025, 31(9): e70593.
6. Volpedo G, Riva A, Nobili L, et al. Gut-immune-brain interactions during neurodevelopment: from a brain-centric to a multisystem perspective. BMC Med, 2025, 23(1): 263.
7. Dahlin M, Prast-Nielsen S. The gut microbiome and epilepsy. EBioMedicine, 2019, 44: 741-746.
8. 馬飛, 李致文, 張琴琴. 癲癇與腸道菌群的相互作用及其臨床意義. 神經疾病與精神衛生, 2025, 25(4): 264-269.
9. 曾慶煌, 魏鳳芳, 許金霞, 等. 癲癇患兒腸道菌群失衡狀況及影響因素分析. 中國病原生物學雜志, 2025, 20(4): 411-414,420.
10. Fang S, Hu N, Zhou C, et al. The comparison of gut microbiota between different types of epilepsy in children. Microb Cell Fact, 2025, 24(1): 64.
11. Yuwattana R, Suparan K, Kerdphoo S, et al. Altered gut microbiome profiles in epileptic children are associated with spectrum of anti-seizure medication responsiveness. Brain Res, 2025, 1849: 149367.
12. Riva A, Sahin E, Volpedo G, et al. Identification of an epilepsy-linked gut microbiota signature in a pediatric rat model of acquired epilepsy. Neurobiol Dis, 2024, 194: 106469.
13. 趙瑞, 高嶺, 王有峰, 等. 柴貝止癇湯通過調控mTOR/HIF-1α通路對癲癇大鼠腸道菌群和Th17/Treg細胞免疫平衡的影響. 中國免疫學雜志, 2025, 41(1): 129-135.
14. 黃璐嫣, 董博思, 彭安嬌, 等. 基于小鼠模型探索腸道菌群在癲癇發病機制中的作用. 現代醫學, 2025, 53(4): 629-638.
15. Mousavi SM, Younesian S, Ejtahed HS. The alteration of gut microbiota composition in patients with epilepsy: a systematic review and meta-analysis. Microbial Pathogenesis, 2025, 199: 107266.
16. Yang H, Liu W, Gao T, et al. Causal associations between gut microbiota, circulating inflammatory proteins, and epilepsy: a multivariable Mendelian randomization study. Front Immunol, 2024, 15: 1438645.
17. Zhang X, Yang Z, Guo J, et al. Associations between the gut microbiota, immune cells, and different subtypes of epilepsy: a Mendelian randomization study. Epilepsia Open, 2025, 10(4): 1133-1146.
18. Kwack DW, Lee S, Lee DH, et al. Changes in gut microbiome can be associated with abrupt seizure exacerbation in epilepsy patients. Clin Neurol Neurosurg, 2024, 246: 108556.
19. Hong B. Gut flora reflects potential risk factors for cognitive dysfunction in patients with epilepsy. J Health Popul Nutr, 2024, 43(1): 155.
20. Ilhan ZE, Brochard V, Lapaque N, et al. Exposure to anti-seizure medications impact growth of gut bacterial species and subsequent host response. Neurobiol Dis, 2022, 167: 105664.
21. Dop C, Kalmutzki MJ, Brochard V, et al. Longitudinal exposure to antiseizure medications shape gut microbial composition, resistome, and metabolome. ISME Commun, 2024, 4(1): ycae123.
22. 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. e13.
23. Dahlin M, Wheelock CE, Prast-Nielsen S. Association between seizure reduction during ketogenic diet treatment of epilepsy and changes in circulatory metabolites and gut microbiota composition. EBioMedicine, 2024, 109: 105400.
24. Grill MF, Maganti RK. Neurotoxic effects associated with antibiotic use: management considerations. Br J Clin Pharmacol, 2011, 72(3): 381-93.
25. Jia Y, Chen H, Zou Q, et al. Gut-brain cholinergic signaling mediates the antiseizure effects of Bacteroides fragilis. Neuron, 2026, 114(6): 1021-1044. e9.
26. 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.
27. Borowicz-Reutt K, Krawczyk M, Czernia J. Ketogenic diet in the treatment of epilepsy. Nutrients, 2024, 16(9): 1258.
28. ?zcan E, Yu KB, Dinh L, et al. Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice. Nat Commun, 2025, 16(1): 987.
29. Yu F, Ji JL, Wang Y, et al. Anti-epileptic and gut-protective effects of trioctanoin and the critical role of gut microbiota in a mouse model of epilepsy. Brain Res Bull, 2025, 227: 111401.
30. Mu C, Kesler M, Chen X, et al. Exogenous ketones exert antiseizure effects and modulate the gut microbiome and mycobiome in a clinically relevant murine model of epilepsy. Epilepsia, 2024, 65(12): 3676-3688.
31. Shakoor MU, Tareen FK, Rehman Z, et al. Probiotics by modulating gut-brain axis together with brivaracetam mitigate seizure progression, behavioral incongruities, and prevented neurodegeneration in pentylenetetrazole-kindled mice. CNS Neurosci Ther, 2024, 30(11): e70078.
32. Ali MH, Raza Z, Rehman Z, et al. Probiotics and pregabalin combination prevented ictogenesis, neurobehavioral abnormalities and neurodegeneration in pentylenetetrazole kindling model of epilepsy. Brain Res, 2025, 1855: 149597.
33. 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, 174: 106668.
34. Matta T, Bishnoi M, Gupta S, et al. GABA-producing Levilactobacillus brevis LAB6 mitigates pentylenetetrazol-induced gut-brain dysregulation in SD rats. J Neurochem, 2025, 169(6): e70141.
35. 岳明, 郜廣冉, 劉俊英. 新型復方益生菌聯合左乙拉西坦治療難治性癲癇患兒的效果及對T淋巴細胞亞群、腸道菌群的影響. 臨床誤診誤治, 2025, 38(5): 42-47.
36. Shariatmadari F, Motaghi A, Arjmand Shabestari A, et al. The effect of synbiotics in the treatment of drug-resistant epilepsy and the parental burden of caregivers: a single-arm pretest-posttest trial. BMC Pediatr, 2024, 24(1): 666.
37. 吳岳彪, 蔡露良, 林魯飛. 酪酸梭菌輔助治療對癲癇患者腸道菌群分布及腸道黏膜通透性的影響. 中國微生態學雜志, 2024, 36(7): 817-820,827.
38. 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.
39. Vendrik KEW, Ooijevaar RE, de Jong PRC, et al. Fecal microbiota transplantation in neurological disorders. Front Cell Infect Microbiol, 2020, 10: 98.
40. Medel-Matus JS, Simpson CA, Ahdoot AI, et al. Modification of post-traumatic epilepsy by fecal microbiota transfer. Epilepsy Behav, 2022, 134: 108860.
41. Zou S, Li Y, Zou Q, et al. Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility. Front Microbiol, 2024, 15: 1403892.
42. Watanangura A, Meller S, Farhat N, et al. Behavioral comorbidities treatment by fecal microbiota transplantation in canine epilepsy: a pilot study of a novel therapeutic approach. Front Vet Sci, 2024, 11: 1385469.
43. Wu Y, Gu D, Li J, et al. Role of the gut microbiota in cefoperazone/sulbactam-induced epilepsy in mice with chronic renal failure. Ren Fail, 2024, 46(2): 2371551.
44. Zou Q, Zhang Y, Zou S, et al. Ciprofloxacin-induced microbiota dysbiosis triggers seizure susceptibility through the microbiota-gut-brain axis. Front Immunol, 2026, 17: 1670694.
45. Stokes JM, Davis JH, Mangat CS, et al. Discovery of a small molecule that inhibits bacterial ribosome biogenesis. eLife, 2014, 3: e03574.
46. Ding M, Lang Y, Shu H, et al. Microbiota-gut-brain axis and epilepsy: a review on mechanisms and potential therapeutics. Front Immunol, 2021, 12: 742449.
47. Takeno S, Sakai T. Involvement of the intestinal microflora in nitrazepam-induced teratogenicity in rats and its relationship to nitroreduction. Teratology, 1991, 44(2): 209-14.
48. Sutter R, Rüegg S, Tschudin-Sutter S. Seizures as adverse events of antibiotic drugs: a systematic review. Neurology, 2015, 85(15): 1332-41.
49. Cannon JP, Lee TA, Clark NM, et al. The risk of seizures among the carbapenems: a meta-analysis. J Antimicrob Chemother, 2014, 69(8): 2043-55.
50. Jia B, Baek JH, Lee JK, et al. Expanding the β-lactamase family in the human microbiome. Adv Sci (Weinh), 2024, 11(46): e2403563.
51. Kebede V, Ravizza T, Balosso S, et al. Early treatment with rifaximin during epileptogenesis reverses gut alterations and reduces seizure duration in a mouse model of acquired epilepsy. Brain Behav Immun, 2024, 119: 363-380.

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Research progress on gut microbiota and epilepsy

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