Skip to content
2000
Volume 23, Issue 11
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

The treatment of epilepsy remains imperfect due to a lack of understanding of its pathogenesis. Although antiseizure medications can control most seizures, up to 30% of patients experience uncontrolled seizures, leading to refractory epilepsy. Therefore, elucidating the pathogenesis of epilepsy and exploring new avenues to design antiepileptic drugs may improve epilepsy treatment. Recent studies have identified an imbalance of the gut microbiota (GM) in both patients with epilepsy and various animal models of epilepsy. In response to this phenomenon, an increasing number of studies have focused on controlling seizures by regulating GM homeostasis, utilizing methods such as dietary restrictions, fecal microbiota transplantation, and the use of prebiotics. Surprisingly, these interventions have shown promising antiepileptic effects, suggesting that GM, through the regulatory role of the microbiota-gut-brain axis (gut-brain axis), may emerge as a novel strategy for treating epilepsy. This review aims to discuss the research progress on the relationship between GM and epilepsy, incorporating the latest clinical studies and animal experiments. We will specifically concentrate on the potential key role of the gut-brain axis in epileptogenesis, epilepsy development, and outcomes of epilepsy. Through a detailed analysis of the underlying mechanisms of the gut-brain axis, we aim to provide a more comprehensive perspective on understanding the pathophysiology of epilepsy and lay the groundwork for the development of new antiepileptic drugs in the future.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cn/10.2174/1570159X23666250414094040
2025-04-15
2025-09-02

  • From This Site

    /content/journals/cn/10.2174/1570159X23666250414094040
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. ChenT.S. LaiM.C. HuangH.Y.I. WuS.N. HuangC.W. Immunity, ion channels and epilepsy.Int. J. Mol. Sci.20222312644610.3390/ijms23126446 35742889
     [Google Scholar]
  2. BeghiE. The epidemiology of epilepsy.Neuroepidemiology202054218519110.1159/000503831 31852003
     [Google Scholar]
  3. FuscoF. PerottoniS. GiordanoC. RivaA. IannoneL.F. De CaroC. RussoE. AlbaniD. StrianoP. The microbiota‐gut‐brain axis and epilepsy from a multidisciplinary perspective: Clinical evidence and technological solutions for improvement of in vitro preclinical models.Bioeng. Transl. Med.202272e1029610.1002/btm2.10296 35600638
     [Google Scholar]
  4. SchefferI.E. BerkovicS. CapovillaG. ConnollyM.B. FrenchJ. GuilhotoL. HirschE. JainS. MathernG.W. MoshéS.L. NordliD.R. PeruccaE. TomsonT. WiebeS. ZhangY.H. ZuberiS.M. ILAE classification of the epilepsies: Position paper of the ILAE commission for classification and terminology.Epilepsia201758451252110.1111/epi.13709 28276062
     [Google Scholar]
  5. LiuY. TianX. KeP. GuJ. MaY. GuoY. XuX. ChenY. YangM. WangX. XiaoF. KIF17 modulates epileptic seizures and membrane expression of the NMDA receptor subunit NR2B.Neurosci. Bull.202238884185610.1007/s12264‑022‑00888‑9 35678994
     [Google Scholar]
  6. KannerA.M. BicchiM.M. Antiseizure medications for adults with epilepsy.JAMA2022327131269128110.1001/jama.2022.3880 35380580
     [Google Scholar]
  7. RaspinC. FaughtE. ArmandJ. BarionF. PollitV. MurphyJ. DanielsonV. An economic evaluation of vagus nerve stimulation as an adjunctive treatment to anti-seizure medications for the treatment of drug resistant epilepsy in the United States.J. Med. Econ.202326118919910.1080/13696998.2023.2171230 36691763
     [Google Scholar]
  8. ChidambaramS.B. EssaM.M. RathipriyaA.G. BishirM. RayB. MahalakshmiA.M. TousifA.H. SakharkarM.K. KashyapR.S. FriedlandR.P. MonaghanT.M. Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle.Pharmacol. Ther.202223110798810.1016/j.pharmthera.2021.107988
     [Google Scholar]
  9. SittipoP. ChoiJ. LeeS. LeeY.K. The function of gut microbiota in immune-related neurological disorders: A review.J. Neuroinflammation202219115410.1186/s12974‑022‑02510‑1 35706008
     [Google Scholar]
  10. Long-SmithC. O’RiordanK.J. ClarkeG. StantonC. DinanT.G. CryanJ.F. Microbiota-gut-brain axis: New therapeutic opportunities.Annu. Rev. Pharmacol. Toxicol.202060147750210.1146/annurev‑pharmtox‑010919‑023628 31506009
     [Google Scholar]
  11. SorboniS.G. MoghaddamH.S. Jafarzadeh-EsfehaniR. SoleimanpourS. A comprehensive review on the role of the gut microbiome in human neurological disorders.Clin. Microbiol. Rev.2022351e00338e2010.1128/CMR.00338‑20 34985325
     [Google Scholar]
  12. HashimotoK. Emerging role of the host microbiome in neuropsychiatric disorders: Overview and future directions.Mol. Psychiatry20232893625363710.1038/s41380‑023‑02287‑6 37845499
     [Google Scholar]
  13. RussoE. The gut microbiota as a biomarker in epilepsy.Neurobiol. Dis.202216310559810.1016/j.nbd.2021.105598 34942335
     [Google Scholar]
  14. WangH.X. WangY.P. Gut Microbiota-brain Axis.Chin. Med. J. (Engl.)2016129192373238010.4103/0366‑6999.190667 27647198
     [Google Scholar]
  15. IllianoP. BrambillaR. ParoliniC. The mutual interplay of gut microbiota, diet and human disease.FEBS J.2020287583385510.1111/febs.15217 31955527
     [Google Scholar]
  16. JavdanB. LopezJ.G. ChankhamjonP. LeeY.J. HullR. WuQ. WangX. ChatterjeeS. DoniaM.S. Personalized mapping of drug metabolism by the human gut microbiome.Cell202018171661167910.1016/j.cell.2020.05.001
     [Google Scholar]
  17. CalabròS. KankowskiS. CesconM. GambarottaG. RaimondoS. Haastert-TaliniK. RonchiG. Impact of gut microbiota on the peripheral nervous system in physiological, regenerative and pathological conditions.Int. J. Mol. Sci.2023249806110.3390/ijms24098061 37175764
     [Google Scholar]
  18. NandwanaV. NandwanaN.K. DasY. SaitoM. PandaT. DasS. AlmaguelF. HosmaneN.S. DasB.C. The role of microbiome in brain development and neurodegenerative diseases.Molecules20222711340210.3390/molecules27113402 35684340
     [Google Scholar]
  19. VicentiniF.A. KeenanC.M. WallaceL.E. WoodsC. CavinJ.B. FlocktonA.R. MacklinW.B. Belkind-GersonJ. HirotaS.A. SharkeyK.A. Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia.Microbiome20219121010.1186/s40168‑021‑01165‑z
     [Google Scholar]
  20. PaikJ. MeekerS. HsuC.C. SeamonsA. PershutkinaO. SnyderJ.M. BrabbT. Maggio-PriceL. Validation studies for germ-free Smad3-/- mice as a bio-assay to test the causative role of fecal microbiomes in IBD.Gut Microbes2020111213110.1080/19490976.2019.1611151 31138018
     [Google Scholar]
  21. HolmesM. FlaminioZ. VardhanM. XuF. LiX. DevinskyO. SaxenaD. Cross talk between drug-resistant epilepsy and the gut microbiome.Epilepsia202061122619262810.1111/epi.16744 33140419
     [Google Scholar]
  22. OsadchiyV. MartinC.R. MayerE.A. The gut-brain axis and the microbiome: Mechanisms and clinical implications.Clin. Gastroenterol. Hepatol.201917232233210.1016/j.cgh.2018.10.002 30292888
     [Google Scholar]
  23. CarabottiM. SciroccoA. MaselliM.A. SeveriC. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems.Ann. Gastroenterol.2015282203209 25830558
     [Google Scholar]
  24. MoraisL.H. SchreiberH.L.IV MazmanianS.K. The gut microbiota-brain axis in behaviour and brain disorders.Nat. Rev. Microbiol.202119424125510.1038/s41579‑020‑00460‑0 33093662
     [Google Scholar]
  25. LiuL. HuhJ.R. ShahK. Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS.EBioMedicine20227710390810.1016/j.ebiom.2022.103908 35255456
     [Google Scholar]
  26. ChatzikonstantinouS. GioulaG. KimiskidisV.K. McKennaJ. MavroudisI. KazisD. The gut microbiome in drug‐resistant epilepsy.Epilepsia Open202161283710.1002/epi4.12461 33681645
     [Google Scholar]
  27. TiwariP. DwivediR. BansalM. TripathiM. DadaR. Role of gut microbiota in neurological disorders and its therapeutic significance.J. Clin. Med.2023124165010.3390/jcm12041650
     [Google Scholar]
  28. Claudino dos SantosJ.C. OliveiraL.F. NoletoF.M. GusmãoC.T.P. BritoG.A.C. VianaG.S.B. Gut-microbiome-brain axis: the crosstalk between the vagus nerve, alpha-synuclein and the brain in Parkinson’s disease.Neural Regen. Res.202318122611261410.4103/1673‑5374.373673 37449597
     [Google Scholar]
  29. HouK. WuZ.X. ChenX.Y. WangJ.Q. ZhangD. XiaoC. ZhuD. KoyaJ.B. WeiL. LiJ. ChenZ.S. Microbiota in health and diseases.Signal Transduct. Target. Ther.20227113510.1038/s41392‑022‑00974‑4 35461318
     [Google Scholar]
  30. GhezziL. CantoniC. RotondoE. GalimbertiD. The Gut microbiome-brain crosstalk in neurodegenerative diseases.Biomedicines2022107148610.3390/biomedicines10071486 35884791
     [Google Scholar]
  31. Al-BeltagiM. SaeedN.K. Epilepsy and the gut: Perpetrator or victim?World J. Gastrointest. Pathophysiol.202213514315610.4291/wjgp.v13.i5.143 36187601
     [Google Scholar]
  32. FüllingC. DinanT.G. CryanJ.F. Gut microbe to brain signaling: What happens in vagus.Neuron20191016998100210.1016/j.neuron.2019.02.008 30897366
     [Google Scholar]
  33. NeedhamB.D. FunabashiM. AdameM.D. WangZ. BoktorJ.C. HaneyJ. WuW.L. RabutC. LadinskyM.S. HwangS.J. GuoY. ZhuQ. GriffithsJ.A. KnightR. BjorkmanP.J. ShapiroM.G. GeschwindD.H. HolschneiderD.P. FischbachM.A. MazmanianS.K. A gut-derived metabolite alters brain activity and anxiety behaviour in mice.Nature2022602789864765310.1038/s41586‑022‑04396‑8 35165440
     [Google Scholar]
  34. WangY. DuW. HuX. YuX. GuoC. JinX. WangW. Targeting the blood-brain barrier to delay aging-accompanied neurological diseases by modulating gut microbiota, circadian rhythms, and their interplays.Acta Pharm. Sin. B202313124667468710.1016/j.apsb.2023.08.009 38045038
     [Google Scholar]
  35. ZhangH. ChenY. WangZ. XieG. LiuM. YuanB. ChaiH. WangW. ChengP. Implications of gut microbiota in neurodegenerative diseases.Front. Immunol.20221378564410.3389/fimmu.2022.785644 35237258
     [Google Scholar]
  36. DashS. SyedY.A. KhanM.R. Understanding the role of the gut microbiome in brain development and its association with neurodevelopmental psychiatric disorders.Front. Cell Dev. Biol.20221088054410.3389/fcell.2022.880544 35493075
     [Google Scholar]
  37. GhezziL. CantoniC. PingetG.V. ZhouY. PiccioL. Targeting the gut to treat multiple sclerosis.J. Clin. Invest.202113113e14377410.1172/JCI143774 34196310
     [Google Scholar]
  38. KeoghC.E. KimD.H.J. PuscedduM.M. KnottsT.A. RabasaG. SladekJ.A. HsiehM.T. HoneycuttM. Brust-MascherI. BarbozaM. GareauM.G. Myelin as a regulator of development of the microbiota-gut-brain axis.Brain Behav. Immun.20219143745010.1016/j.bbi.2020.11.001 33157256
     [Google Scholar]
  39. ZhouX. BaumannR. GaoX. MendozaM. SinghS. Katz SandI. XiaZ. CoxL.M. ChitnisT. YoonH. MolesL. CaillierS.J. SantanielloA. AckermannG. HarroudA. LincolnR. GomezR. GonzálezP.A. DiggaE. HakimD.J. Vazquez-BaezaY. SomanK. WartoS. HumphreyG. FarezM. GerdesL.A. OksenbergJ.R. ZamvilS.S. ChandranS. ConnickP. OtaeguiD. Castillo-TriviñoT. HauserS.L. GelfandJ.M. WeinerH.L. HohlfeldR. WekerleH. GravesJ. Bar-OrA. CreeB.A.C. CorrealeJ. KnightR. BaranziniS.E. Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course.Cell20221851934673486.e1610.1016/j.cell.2022.08.021 36113426
     [Google Scholar]
  40. NosiD. LanaD. GiovanniniM.G. DelfinoG. Zecchi-OrlandiniS. Neuroinflammation: Integrated nervous tissue response through intercellular interactions at the “whole system” scale.Cells2021105119510.3390/cells10051195 34068375
     [Google Scholar]
  41. HeH. HeH. MoL. YouZ. ZhangJ. Priming of microglia with dysfunctional gut microbiota impairs hippocampal neurogenesis and fosters stress vulnerability of mice.Brain Behav. Immun.202411528029410.1016/j.bbi.2023.10.031 37914097
     [Google Scholar]
  42. HoffmanJ.M. MargolisK.G. Building community in the gut: a role for mucosal serotonin.Nat. Rev. Gastroenterol. Hepatol.20201716810.1038/s41575‑019‑0227‑6 31624372
     [Google Scholar]
  43. ZhaiL. HuangC. NingZ. ZhangY. ZhuangM. YangW. WangX. WangJ. ZhangL. XiaoH. ZhaoL. AsthanaP. LamY.Y. ChowC.F.W. HuangJ. YuanS. ChanK.M. YuanC.S. LauJ.Y.N. WongH.L.X. BianZ. Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis.Cell Host Microbe20233113344.e510.1016/j.chom.2022.11.006 36495868
     [Google Scholar]
  44. EngevikM.A. LuckB. VisuthranukulC. IhekweazuF.D. EngevikA.C. ShiZ. DanhofH.A. Chang-GrahamA.L. HallA. EndresB.T. HaidacherS.J. HorvathT.D. HaagA.M. DevarajS. GareyK.W. BrittonR.A. HyserJ.M. ShroyerN.F. VersalovicJ. human-derived Bifidobacterium dentium modulates the mammalian serotonergic system and gut-brain axis.Cell. Mol. Gastroenterol. Hepatol.202111122124810.1016/j.jcmgh.2020.08.002 32795610
     [Google Scholar]
  45. BranisteV. Al-AsmakhM. KowalC. AnuarF. AbbaspourA. TóthM. KoreckaA. BakocevicN. NgL.G. KunduP. GulyásB. HalldinC. HultenbyK. NilssonH. HebertH. VolpeB.T. DiamondB. PetterssonS. The gut microbiota influences blood-brain barrier permeability in mice.Sci. Transl. Med.20146263263ra15810.1126/scitranslmed.3009759 25411471
     [Google Scholar]
  46. BegumN. MandhareA. TryphenaK.P. SrivastavaS. ShaikhM.F. SinghS.B. KhatriD.K. Epigenetics in depression and gut-brain axis: A molecular crosstalk.Front. Aging Neurosci.202214104833310.3389/fnagi.2022.1048333 36583185
     [Google Scholar]
  47. SocałaK. DoboszewskaU. SzopaA. SerefkoA. WłodarczykM. ZielińskaA. PoleszakE. FichnaJ. WlaźP. The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders.Pharmacol. Res.202117210584010.1016/j.phrs.2021.105840 34450312
     [Google Scholar]
  48. LinP. LinA. TaoK. YangM. YeQ. ChenH. ChenY. MaY. LinZ. HeM. WangX. TianX. Intestinal Klebsiella pneumoniae infection enhances susceptibility to epileptic seizure which can be reduced by microglia activation.Cell Death Discov.20217117510.1038/s41420‑021‑00559‑0 34234109
     [Google Scholar]
  49. DongL. ZhengQ. ChengY. ZhouM. WangM. XuJ. XuZ. WuG. YuY. YeL. FengZ. Gut microbial characteristics of adult patients with epilepsy.Front. Neurosci.20221680353810.3389/fnins.2022.803538 35250450
     [Google Scholar]
  50. ChenC. LiaoJ. XiaY. LiuX. JonesR. HaranJ. McCormickB. SampsonT.R. AlamA. YeK. Gut microbiota regulate Alzheimer’s disease pathologies and cognitive disorders via PUFA-associated neuroinflammation.Gut202271112233225210.1136/gutjnl‑2021‑326269
     [Google Scholar]
  51. ZhongH.J. WangS.Q. ZhangR.X. ZhuangY.P. LiL. YiS.Z. LiY. WuL. DingY. ZhangJ. XieX. HeX.X. WuQ. Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA.Transl. Neurodegener.20231215810.1186/s40035‑023‑00391‑9 38093327
     [Google Scholar]
  52. HsiaoE.Y. McBrideS.W. HsienS. SharonG. HydeE.R. McCueT. CodelliJ.A. ChowJ. ReismanS.E. PetrosinoJ.F. PattersonP.H. MazmanianS.K. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.Cell201315571451146310.1016/j.cell.2013.11.024 24315484
     [Google Scholar]
  53. CarmelJ. GhanayemN. MayoufR. SaleevN. ChaterjeeI. GetselterD. TikhonovE. TurjemanS. ShaalanM. KhateebS. KuzminskyA. Kvetniy-FerdmanN. KronosT. Bretler-ZagerT. KorenO. ElliottE. Bacteroides is increased in an autism cohort and induces autism-relevant behavioral changes in mice in a sex-dependent manner.NPJ Biofilms Microbiomes20239110310.1038/s41522‑023‑00469‑2 38110423
     [Google Scholar]
  54. BonhamK.S. Fahur BottinoG. McCannS.H. BeaucheminJ. WeisseE. BarryF. Cano LorenteR. HuttenhowerC. BruchhageM. D’SaV. DeoniS. Klepac-CerajV. Gut-resident microorganisms and their genes are associated with cognition and neuroanatomy in children.Sci. Adv.2023951eadi049710.1126/sciadv.adi0497 38134274
     [Google Scholar]
  55. Szandruk-BenderM. WiatrakB. SzelągA. The risk of developing Alzheimer’s disease and Parkinson’s disease in patients with inflammatory bowel disease: A meta-analysis.J. Clin. Med.20221113370410.3390/jcm11133704 35806985
     [Google Scholar]
  56. ChenG. ZhouX. ZhuY. ShiW. KongL. Gut microbiome characteristics in subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease: A systematic review and meta‐analysis.Eur. J. Neurol.202330113568358010.1111/ene.15961 37399128
     [Google Scholar]
  57. MaQ. XingC. LongW. WangH.Y. LiuQ. WangR.F. Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis.J. Neuroinflammation20191615310.1186/s12974‑019‑1434‑3 30823925
     [Google Scholar]
  58. ChaudhryT.S. SenapatiS.G. GadamS. MannamH.P.S.S. VorugantiH.V. AbbasiZ. AbhinavT. ChallaA.B. PallipamuN. BheemisettyN. ArunachalamS.P. The impact of microbiota on the gut-brain axis: Examining the complex interplay and implications.J. Clin. Med.20231216523110.3390/jcm12165231 37629273
     [Google Scholar]
  59. BojovićK. IgnjatovićÐ. Soković BajićS. Vojnović MilutinovićD. TomićM. GolićN. TolinačkiM. Gut microbiota dysbiosis associated with altered production of short chain fatty acids in children with neurodevelopmental disorders.Front. Cell. Infect. Microbiol.20201022310.3389/fcimb.2020.00223 32509596
     [Google Scholar]
  60. LiuS. MenX. GuoY. CaiW. WuR. GaoR. ZhongW. GuoH. RuanH. ChouS. MaiJ. PingS. JiangC. ZhouH. MouX. ZhaoW. LuZ. Gut microbes exacerbate systemic inflammation and behavior disorders in neurologic disease CADASIL.Microbiome202311120210.1186/s40168‑023‑01638‑3 37684694
     [Google Scholar]
  61. OlsonC.A. VuongH.E. YanoJ.M. LiangQ.Y. NusbaumD.J. HsiaoE.Y. The gut microbiota mediates the anti-seizure effects of the ketogenic diet.Cell201817371728174110.1016/j.cell.2018.04.027
     [Google Scholar]
  62. ZhuH. WangW. LiY. The interplay between microbiota and brain-gut axis in epilepsy treatment.Front. Pharmacol.202415127655110.3389/fphar.2024.1276551 38344171
     [Google Scholar]
  63. ŞafakB. AltunanB. TopçuB. ErenT.A. The gut microbiome in epilepsy.Microb. Pathog.202013910385310.1016/j.micpath.2019.103853 31730997
     [Google Scholar]
  64. ZhouC. GongS. XiangS. LiangL. HuX. HuangR. LiaoZ. MaY. XiaoZ. QiuJ. Changes and significance of gut microbiota in children with focal epilepsy before and after treatment.Front. Cell. Infect. Microbiol.20221296547110.3389/fcimb.2022.965471 36405958
     [Google Scholar]
  65. XieG. ZhouQ. QiuC.Z. DaiW.K. WangH.P. LiY.H. LiaoJ.X. LuX.G. LinS.F. YeJ.H. MaZ.Y. WangW.J. Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy.World J. Gastroenterol.201723336164617110.3748/wjg.v23.i33.6164 28970732
     [Google Scholar]
  66. DahlinM. SingletonS.S. DavidJ.A. BasuchoudharyA. WickströmR. MazumderR. Prast-NielsenS. Higher levels of Bifidobacteria and tumor necrosis factor in children with drug-resistant epilepsy are associated with anti-seizure response to the ketogenic diet.EBioMedicine20228010406110.1016/j.ebiom.2022.104061 35598439
     [Google Scholar]
  67. MengoniF. SalariV. KosenkovaI. TsenovG. DonadelliM. MalerbaG. BertiniG. Del GalloF. FabeneP.F. Gut microbiota modulates seizure susceptibility.Epilepsia2021629e153e15710.1111/epi.17009 34324703
     [Google Scholar]
  68. ZhaiJ. WangC. JinL. LiuF. XiaoY. GuH. LiuM. ChenY. Gut Microbiota metabolites mediate bax to reduce neuronal apoptosis via cGAS/STING axis in epilepsy.Mol. Neurobiol.20231610.1007/s12035‑023‑03545‑y 37605097
     [Google Scholar]
  69. De CaroC. LeoA. NesciV. GhelardiniC. di Cesare MannelliL. StrianoP. AvaglianoC. CalignanoA. MainardiP. ConstantiA. CitraroR. De SarroG. RussoE. Intestinal inflammation increases convulsant activity and reduces antiepileptic drug efficacy in a mouse model of epilepsy.Sci. Rep.2019911398310.1038/s41598‑019‑50542‑0 31562378
     [Google Scholar]
  70. CitraroR. LemboF. De CaroC. TallaricoM. CorettiL. IannoneL.F. LeoA. PalumboD. CuomoM. BuomminoE. NesciV. MarascioN. IannoneM. QuirinoA. RussoR. CalignanoA. ConstantiA. RussoE. De SarroG. First evidence of altered microbiota and intestinal damage and their link to absence epilepsy in a genetic animal model, the WAG/Rij rat.Epilepsia202162252954110.1111/epi.16813 33428780
     [Google Scholar]
  71. Medel-MatusJ.S. LagishettyV. Santana-GomezC. ShinD. MowreyW. StabaR.J. GalanopoulouA.S. SankarR. JacobsJ.P. MazaratiA.M. Susceptibility to epilepsy after traumatic brain injury is associated with preexistent gut microbiome profile.Epilepsia20226371835184810.1111/epi.17248 35366338
     [Google Scholar]
  72. KimS. ParkS. ChoiT.G. KimS.S. Role of short chain fatty acids in epilepsy and potential benefits of probiotics and prebiotics: Targeting “health” of epileptic patients.Nutrients20221414298210.3390/nu14142982 35889939
     [Google Scholar]
  73. YuanX. TangH. WuR. LiX. JiangH. LiuZ. ZhangZ. Short-chain fatty acids calibrate RARα activity regulating food sensitization.Front. Immunol.20211273765810.3389/fimmu.2021.737658 34721398
     [Google Scholar]
  74. WangY. ZhuoZ. WangH. Epilepsy, gut microbiota, and circadian rhythm.Front. Neurol.202314115735810.3389/fneur.2023.1157358 37273718
     [Google Scholar]
  75. MorísG. Inflammatory bowel disease: An increased risk factor for neurologic complications.World J. Gastroenterol.20142051228123710.3748/wjg.v20.i5.1228 24574797
     [Google Scholar]
  76. DingM. LangY. ShuH. ShaoJ. CuiL. Microbiota-gut-brain axis and epilepsy: A review on mechanisms and potential therapeutics.Front. Immunol.20211274244910.3389/fimmu.2021.742449 34707612
     [Google Scholar]
  77. ZhangL. LiS. TaiZ. YuC. XuZ. Gut microbes regulate innate immunity and epilepsy.Front. Neurosci.20221687019710.3389/fnins.2022.870197 35720723
     [Google Scholar]
  78. OliveiraM.E.T. PaulinoG.V.B. dos Santos JúniorE.D. da Silva OliveiraF.A. MeloV.M.M. UrsulinoJ.S. de AquinoT.M. ShettyA.K. LandellM.F. GitaíD.L.G. Multi-omic analysis of the gut microbiome in rats with lithium-pilocarpine-induced temporal lobe epilepsy.Mol. Neurobiol.202259106429644610.1007/s12035‑022‑02984‑3 35962889
     [Google Scholar]
  79. GongX. LiuL. LiX. XiongJ. XuJ. MaoD. LiuL. Neuroprotection of cannabidiol in epileptic rats: Gut microbiome and metabolome sequencing.Front. Nutr.20229102845910.3389/fnut.2022.1028459 36466385
     [Google Scholar]
  80. JinZ. DongJ. WangY. LiuY. Exploring the potential of vagus nerve stimulation in treating brain diseases: a review of immunologic benefits and neuroprotective efficacy.Eur. J. Med. Res.202328144410.1186/s40001‑023‑01439‑2 37853458
     [Google Scholar]
  81. PengA. QiuX. LaiW. LiW. ZhangL. ZhuX. HeS. DuanJ. ChenL. Altered composition of the gut microbiome in patients with drug-resistant epilepsy.Epilepsy Res.201814710210710.1016/j.eplepsyres.2018.09.013 30291996
     [Google Scholar]
  82. LeeH. LeeS. LeeD.H. KimD.W. A comparison of the gut microbiota among adult patients with drug-responsive and drug-resistant epilepsy: An exploratory study.Epilepsy Res.202117210660110.1016/j.eplepsyres.2021.106601 33713890
     [Google Scholar]
  83. AvorioF. Cerulli IrelliE. MoranoA. FanellaM. OrlandoB. AlbiniM. BasiliL.M. RuffoloG. FattouchJ. ManfrediM. RussoE. StrianoP. CarabottiM. GiallonardoA.T. SeveriC. Di BonaventuraC. Functional gastrointestinal disorders in patients with epilepsy: Reciprocal influence and impact on seizure occurrence.Front. Neurol.20211270512610.3389/fneur.2021.705126 34421803
     [Google Scholar]
  84. WangJ. HuangL.I. LiH. ChenG. YangL. WangD. HanH. ZhengG. WangX. LiangJ. HeW. FangF. LiaoJ. SunD. Effects of ketogenic diet on the classification and functional composition of intestinal flora in children with mitochondrial epilepsy.Front. Neurol.202314123725510.3389/fneur.2023.1237255 37588668
     [Google Scholar]
  85. LumG.R. OlsonC.A. HsiaoE.Y. Emerging roles for the intestinal microbiome in epilepsy.Neurobiol. Dis.202013510457610.1016/j.nbd.2019.104576 31445165
     [Google Scholar]
  86. Medel-MatusJ.S. SimpsonC.A. AhdootA.I. ShinD. SankarR. JacobsJ.P. MazaratiA.M. Modification of post-traumatic epilepsy by fecal microbiota transfer.Epilepsy Behav.202213410886010.1016/j.yebeh.2022.108860 35914438
     [Google Scholar]
  87. ChenX. ZhangW. LinZ. ZhengC. ChenS. ZhouH. LiuZ. Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments.Front. Cell. Infect. Microbiol.202313110318910.3389/fcimb.2023.1103189 37113132
     [Google Scholar]
  88. HeZ. CuiB.T. ZhangT. LiP. LongC.Y. JiG.Z. ZhangF.M. Fecal microbiota transplantation cured epilepsy in a case with Crohn’s disease: The first report.World J. Gastroenterol.201723193565356810.3748/wjg.v23.i19.3565 28596693
     [Google Scholar]
  89. Medel-MatusJ.S. ShinD. DorfmanE. SankarR. MazaratiA. Facilitation of kindling epileptogenesis by chronic stress may be mediated by intestinal microbiome.Epilepsia Open20183229029410.1002/epi4.12114 29881810
     [Google Scholar]
  90. HornJ. MayerD.E. ChenS. MayerE.A. Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders.Transl. Psychiatry202212116410.1038/s41398‑022‑01922‑0
     [Google Scholar]
  91. ZmoraN. SuezJ. ElinavE. You are what you eat: Diet, health and the gut microbiota.Nat. Rev. Gastroenterol. Hepatol.2019161355610.1038/s41575‑018‑0061‑2 30262901
     [Google Scholar]
  92. DahlinM. Prast-NielsenS. The gut microbiome and epilepsy.EBioMedicine20194474174610.1016/j.ebiom.2019.05.024 31160269
     [Google Scholar]
  93. PietrzakD. KasperekK. RękawekP. Piątkowska-ChmielI. The therapeutic role of ketogenic diet in neurological disorders.Nutrients2022149195210.3390/nu14091952 35565918
     [Google Scholar]
  94. MuC. PochakomA. ReimerR.A. ChoudharyA. WangM. RhoJ.M. ScantleburyM.H. ShearerJ. Addition of prebiotics to the ketogenic diet improves metabolic profile but does not affect seizures in a rodent model of infantile spasms syndrome.Nutrients20221411221010.3390/nu14112210 35684010
     [Google Scholar]
  95. LindefeldtM. EngA. DarbanH. BjerknerA. ZetterströmC.K. AllanderT. AnderssonB. BorensteinE. DahlinM. Prast-NielsenS. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy.NPJ Biofilms Microbiomes201951510.1038/s41522‑018‑0073‑2 30701077
     [Google Scholar]
  96. YangY. ChangY. WuY. LiuH. LiuQ. KangZ. WuM. YinH. DuanJ. A homogeneous polysaccharide from Lycium barbarum: Structural characterizations, anti-obesity effects and impacts on gut microbiota.Int. J. Biol. Macromol.20211832074208710.1016/j.ijbiomac.2021.05.209 34097961
     [Google Scholar]
  97. GaoL.L. MaJ.M. FanY.N. ZhangY.N. GeR. TaoX.J. ZhangM.W. GaoQ.H. YangJ.J. Lycium barbarum polysaccharide combined with aerobic exercise ameliorated nonalcoholic fatty liver disease through restoring gut microbiota, intestinal barrier and inhibiting hepatic inflammation.Int. J. Biol. Macromol.20211831379139210.1016/j.ijbiomac.2021.05.066 33992651
     [Google Scholar]
  98. YingM. YuQ. ZhengB. WangH. WangJ. ChenS. NieS. XieM. Cultured Cordyceps sinensis polysaccharides modulate intestinal mucosal immunity and gut microbiota in cyclophosphamide-treated mice.Carbohydr. Polym.202023511595710.1016/j.carbpol.2020.115957 32122493
     [Google Scholar]
  99. PorterN.T. MartensE.C. The Critical Roles of Polysaccharides in Gut Microbial Ecology and Physiology.Annu. Rev. Microbiol.201771134936910.1146/annurev‑micro‑102215‑095316 28657886
     [Google Scholar]
  100. HammermanC. Bin-NunA. KaplanM. Safety of probiotics: comparison of two popular strains.BMJ200633375761006100810.1136/bmj.39010.630799.BE 17095783
     [Google Scholar]
  101. LinW.Y. LinJ.H. KuoY.W. ChiangP.F.R. HoH.H. Probiotics and their metabolites reduce oxidative stress in middle-aged mice.Curr. Microbiol.202279410410.1007/s00284‑022‑02783‑y 35157139
     [Google Scholar]
  102. SongW. YanX. ZhaiY. RenJ. WuT. GuoH. SongY. LiX. GuoY. Probiotics attenuate valproate-induced liver steatosis and oxidative stress in mice.PLoS One20231811e029436310.1371/journal.pone.0294363 37971986
     [Google Scholar]
  103. SnigdhaS. HaK. TsaiP. DinanT.G. BartosJ.D. ShahidM. Probiotics: Potential novel therapeutics for microbiota-gut-brain axis dysfunction across gender and lifespan.Pharmacol. Ther.202223110797810.1016/j.pharmthera.2021.107978 34492236
     [Google Scholar]
  104. ZubarevaO.E. DyominaA.V. KovalenkoA.A. RoginskayaA.I. Melik-KasumovT.B. KorneevaM.A. ChuprinaA.V. ZhabinskayaA.A. KolyhanS.A. ZakharovaM.V. GryaznovaM.O. ZaitsevA.V. Beneficial effects of probiotic Bifidobacterium longum in a lithium-pilocarpine model of temporal lobe epilepsy in rats.Int. J. Mol. Sci.2023249845110.3390/ijms24098451 37176158
     [Google Scholar]
  105. BagheriS. HeydariA. AlinaghipourA. SalamiM. Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ-induced chemical kindling.Epilepsy Behav.201995435010.1016/j.yebeh.2019.03.038 31026781
     [Google Scholar]
  106. WangX. MaR. LiuX. ZhangY. Effects of long-term supplementation of probiotics on cognitive function and emotion in temporal lobe epilepsy.Front. Neurol.20221394859910.3389/fneur.2022.948599 35928136
     [Google Scholar]
  107. FuhrenJ. SchwalbeM. BoekhorstJ. RöschC. ScholsH.A. KleerebezemM. Dietary calcium phosphate strongly impacts gut microbiome changes elicited by inulin and galacto-oligosaccharides consumption.Microbiome20219121810.1186/s40168‑021‑01148‑0 34732247
     [Google Scholar]
  108. IannoneL.F. Gómez-EguílazM. De CaroC. Gut microbiota manipulation as an epilepsy treatment.Neurobiol. Dis.202217410589710.1016/j.nbd.2022.105897 36257595
     [Google Scholar]
  109. YadavM.K. KumariI. SinghB. SharmaK.K. TiwariS.K. Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics.Appl. Microbiol. Biotechnol.2022106250552110.1007/s00253‑021‑11646‑8 35015145
     [Google Scholar]
  110. WangX. YangC. YangL. ZhangY. Modulating the gut microbiota ameliorates spontaneous seizures and cognitive deficits in rats with kainic acid-induced status epilepticus by inhibiting inflammation and oxidative stress.Front. Nutr.2022998584110.3389/fnut.2022.985841 36105577
     [Google Scholar]
  111. LiH.Y. ZhouD.D. GanR.Y. HuangS.Y. ZhaoC.N. ShangA. XuX.Y. LiH.B. Effects and mechanisms of probiotics, prebiotics, synbiotics, and postbiotics on metabolic diseases targeting gut microbiota: A narrative review.Nutrients2021139321110.3390/nu13093211 34579087
     [Google Scholar]
  112. JinC.J. EngstlerA.J. SellmannC. ZiegenhardtD. LandmannM. KanuriG. LounisH. SchröderM. VetterW. BergheimI. Sodium butyrate protects mice from the development of the early signs of non-alcoholic fatty liver disease: Role of melatonin and lipid peroxidation.Br. J. Nutr.2016116101682169310.1017/S0007114516004025 27876107
     [Google Scholar]
  113. LiuY.J. ZhuangJ. ZhuH.Y. ShenY.X. TanZ.L. ZhouJ.N. Cultured rat cortical astrocytes synthesize melatonin: absence of a diurnal rhythm.J. Pineal Res.200743323223810.1111/j.1600‑079X.2007.00466.x 17803519
     [Google Scholar]
  114. AndersonG. MaesM. Local melatonin regulates inflammation resolution: A common factor in neurodegenerative, psychiatric and systemic inflammatory disorders.CNS Neurol. Disord. Drug Targets201413581782710.2174/1871527313666140711091400 25012620
     [Google Scholar]
  115. SinghS. SinghT.G. Emerging perspectives on mitochondrial dysfunctioning and inflammation in epileptogenesis.Inflamm. Res.20217010-121027104210.1007/s00011‑021‑01511‑9 34652489
     [Google Scholar]
  116. AndersonG. A more holistic perspective of Alzheimer’s disease: roles of gut microbiome, adipocytes, HPA axis, melatonergic pathway and astrocyte mitochondria in the emergence of autoimmunity. Front.Biosci-Landmrk.2023281235510.31083/j.fbl2812355 38179773
     [Google Scholar]
  117. AndersonG. OjalaJ.O. Alzheimer’s and seizures: Interleukin-18, indoleamine 2,3-dioxygenase and quinolinic Acid.Int. J. Tryptophan Res.20103IJTR.S460310.4137/IJTR.S4603 22084597
     [Google Scholar]
  118. HuaX. ZhangJ. ChenJ. FengR. ZhangL. ChenX. JiangQ. YangC. LiangC. Sodium butyrate alleviates experimental autoimmune prostatitis by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO‐1 pathway.Prostate202484766668110.1002/pros.24683 38444115
     [Google Scholar]
  119. KarkiP. WebbA. SmithK. JohnsonJ.Jr LeeK. SonD.S. AschnerM. LeeE. Yin Yang 1 is a repressor of glutamate transporter EAAT2, and it mediates manganese-induced decrease of EAAT2 expression in astrocytes.Mol. Cell. Biol.20143471280128910.1128/MCB.01176‑13 24469401
     [Google Scholar]
/content/journals/cn/10.2174/1570159X23666250414094040
Loading
Microbiota-gut-brain Axis: Novel Potential Pathways for Developing Antiepileptogenic Drugs
Curr. Neuropharmacol. 23, 1315 (2025); https://doi.org/10.2174/1570159X23666250414094040
/content/journals/cn/10.2174/1570159X23666250414094040
/content/journals/cn/10.2174/1570159X23666250414094040
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): antiepileptic drug; antiseizure medication; epilepsy; epilepsy treatment; epileptogenesis; Gut microbiota; microbiota-gut-brain axis

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test