Epilepsy as a chronic neurological disorder is characterized by recurrent, unprovoked epileptic seizures. In about half of the people who suffer from epilepsy, the root cause of the disorder is unknown. In the other cases, different factors can cause the onset of epilepsy. In recent years, the role of gut microbiota has been recognized in many neurological disorders, including epilepsy. These data are based on studies of the gut microbiota-brain axis, a relationship starting by a dysbiosis followed by an alteration of brain functions. Interestingly, epileptic patients may show signs of dysbiosis, therefore the normalization of the gut microbiota may lead to improvement of epilepsy and to greater efficacy of anticonvulsant drugs. In this descriptive review, we analyze the evidences for the role of gut microbiota in epilepsy and hypothesize a mechanism of action of these microorganisms in the pathogenesis and treatment of the disease. Human studies revealed an increased prevalence of Firmicutes in patients with refractory epilepsy. Exposure to various compounds can change microbiota composition, decreasing or exacerbating epileptic seizures. These include antibiotics, epileptic drugs, probiotics and ketogenic diet. Finally, we hypothesize that physical activity may play a role in epilepsy through the modulation of the gut microbiota.

Department of Neurosurgery Faculty of Medicine Charles University 500 03 Hradec Kralove Czech Republic

Department of Neurosurgery Na Homolce Hospital 150 00 Prague Czech Republic

International Clinical Research Center St Anne's University Hospital Brno 656 91 Brno Czech Republic

Memory Clinic Department of Neurology 2nd Faculty of Medicine Motol University Hospital Charles University 110 00 Prague Czech Republic

Motol Epilepsy Center Department of Neurology 2nd Faculty of Medicine Motol University Hospital Charles University 110 00 Prague Czech Republic

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Scheffer I.E., Berkovic S., Capovilla G., Connolly M.B., French J., Guilhoto L., Hirsch E., Jain S., Mathern G.W., Moshé S.L., et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:512–521. doi: 10.1111/epi.13709. PubMed DOI PMC

Mbizvo G.K., Bennett K., Simpson C.R., Duncan S.E., Chin R.F.M. Epilepsy-related and other causes of mortality in people with epilepsy: A systematic review of systematic reviews. Epilepsy Res. 2019;157:106192. doi: 10.1016/j.eplepsyres.2019.106192. PubMed DOI

Shorvon S.D. The causes of epilepsy: Changing concepts of etiology of epilepsy over the past 150 years. Epilepsia. 2011;52:1033–1044. doi: 10.1111/j.1528-1167.2011.03051.x. PubMed DOI

Ahmad S., Khanna R., Sani S. Surgical Treatments of Epilepsy. Semin. Neurol. 2020;40:696–707. doi: 10.1055/s-0040-1719072. PubMed DOI

Burakgazi E., French J.A. Treatment of epilepsy in adults. Epileptic Disord. 2016;18:228–239. doi: 10.1684/epd.2016.0836. PubMed DOI

Cox L.M., Weiner H.L. Microbiota Signaling Pathways that Influence Neurologic Disease. Neurotherapeutics. 2018;15:135–145. doi: 10.1007/s13311-017-0598-8. PubMed DOI PMC

Lum G.R., Olson C.A., Hsiao E.Y. Emerging roles for the intestinal microbiome in epilepsy. Neurobiol. Dis. 2020;135:104576. doi: 10.1016/j.nbd.2019.104576. PubMed DOI

Dahlin M., Prast-Nielsen S. The gut microbiome and epilepsy. EBioMedicine. 2019;44:741–746. doi: 10.1016/j.ebiom.2019.05.024. PubMed DOI PMC

Holmes M., Flaminio Z., Vardhan M., Xu F., Li X., Devinsky O., Saxena D. Cross talk between drug-resistant epilepsy and the gut microbiome. Epilepsia. 2020;61:2619–2628. doi: 10.1111/epi.16744. PubMed DOI

Yamashiro Y. Gut Microbiota in Health and Disease. Ann. Nutr. Metab. 2017;71:242–246. doi: 10.1159/000481627. PubMed DOI

Rinninella E., Raoul P., Cintoni M., Franceschi F., Miggiano G., Gasbarrini A., Mele M. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms. 2019;7:14. doi: 10.3390/microorganisms7010014. PubMed DOI PMC

Zocco M.A., Ainora M.E., Gasbarrini G., Gasbarrini A. Bacteroides thetaiotaomicron in the gut: Molecular aspects of their interaction. Dig. Liver Dis. 2007;39:707–712. doi: 10.1016/j.dld.2007.04.003. PubMed DOI

Czepiel J., Dróżdż M., Pituch H., Kuijper E.J., Perucki W., Mielimonka A., Goldman S., Wultańska D., Garlicki A., Biesiada G. Clostridium difficile infection: Review. Eur. J. Clin. Microbiol. Infect. Dis. 2019;38:1211–1221. doi: 10.1007/s10096-019-03539-6. PubMed DOI PMC

Jakobsson H.E., Rodríguez-Piñeiro A.M., Schütte A., Ermund A., Boysen P., Bemark M., Sommer F., Bäckhed F., Hansson G.C., Johansson M.E. The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep. 2015;16:164–177. doi: 10.15252/embr.201439263. PubMed DOI PMC

Mendes V., Galvão I., Vieira A.T. Mechanisms by Which the Gut Microbiota Influences Cytokine Production and Modulates Host Inflammatory Responses. J. Interf. Cytokine Res. 2019;39:393–409. doi: 10.1089/jir.2019.0011. PubMed DOI

Gareau M.G. Microbiota-Gut-Brain Axis and Cognitive Function. Adv. Exp. Med. Biol. 2014;817:357–371. PubMed

Dinan T.G., Cryan J.F. The Microbiome-Gut-Brain Axis in Health and Disease. Gastroenterol. Clin. N. Am. 2017;46:77–89. doi: 10.1016/j.gtc.2016.09.007. PubMed DOI

Carabotti M., Scirocco A., Maselli M.A., Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. 2015;28:203–209. PubMed PMC

Warner B.B. The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders. Pediatr. Res. 2019;85:216–224. doi: 10.1038/s41390-018-0191-9. PubMed DOI

Quigley E.M.M. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases. Curr. Neurol. Neurosci. Rep. 2017;17:94. doi: 10.1007/s11910-017-0802-6. PubMed DOI

Angelucci F., Cechova K., Amlerova J., Hort J. Antibiotics, gut microbiota, and Alzheimer’s disease. J. Neuroinflamm. 2019;16:108. doi: 10.1186/s12974-019-1494-4. PubMed DOI PMC

Wang H.X., Wang Y.P. Gut microbiota-brain axis. Chin. Med. J. Engl. 2016;129:2373–2380. doi: 10.4103/0366-6999.190667. PubMed DOI PMC

Silva Y.P., Bernardi A., Frozza R.L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol. 2020;11:25. doi: 10.3389/fendo.2020.00025. PubMed DOI PMC

Tan A.H., Chong C.W., Lim S., Yap I.K.S., Teh C.S.J., Loke M.F., Song S., Tan J.Y., Ang B.H., Tan Y.Q., et al. Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi-Omics. Ann. Neurol. 2021;89:546–559. doi: 10.1002/ana.25982. PubMed DOI

Bercik P., Denou E., Collins J., Jackson W., Lu J., Jury J., Deng Y., Blennerhassett P., Macri J., McCoy K.D., et al. The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice. Gastroenterology. 2011;141:599–609.e3. doi: 10.1053/j.gastro.2011.04.052. PubMed DOI

Simpson C.A., Diaz-Arteche C., Eliby D., Schwartz O.S., Simmons J.G., Cowan C.S.M. The gut microbiota in anxiety and depression—A systematic review. Clin. Psychol. Rev. 2021;83:101943. doi: 10.1016/j.cpr.2020.101943. PubMed DOI

Liu B., He Y., Wang M., Liu J., Ju Y., Zhang Y., Liu T., Li L., Li Q. Efficacy of probiotics on anxiety-A meta-analysis of randomized controlled trials. Depress. Anxiety. 2018;35:935–945. doi: 10.1002/da.22811. PubMed DOI

Barichella M., Severgnini M., Cilia R., Cassani E., Bolliri C., Caronni S., Ferri V., Cancello R., Ceccarani C., Faierman S., et al. Unraveling gut microbiota in Parkinson’s disease and atypical parkinsonism. Mov. Disord. 2018;34:396–405. doi: 10.1002/mds.27581. PubMed DOI

Franceschi F., Ojetti V., Candelli M., Covino M., Cardone S., Potenza A., Simeoni B., Gabrielli M., Sabia L., Gasbarrini G., et al. Microbes and Alzheimer’ disease: Lessons from H. pylori and GUT microbiota. Eur. Rev. Med. Pharmacol. Sci. 2019;23:426–430. PubMed

Sampson T.R., Debelius J.W., Thron T., Janssen S., Shastri G.G., Ilhan Z.E., Challis C., Schretter C.E., Rocha S., Gradinaru V., et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell. 2016;167:1469–1480.e12. doi: 10.1016/j.cell.2016.11.018. PubMed DOI PMC

Vogt N.M., Kerby R.L., Dill-McFarland K.A., Harding S.J., Merluzzi A.P., Johnson S.C., Carlsson C.M., Asthana S., Zetterberg H., Blennow K., et al. Gut microbiome alterations in Alzheimer’s disease. Sci. Rep. 2017;7:13537. doi: 10.1038/s41598-017-13601-y. PubMed DOI PMC

Cekanaviciute E., Yoo B.B., Runia T.F., Debelius J.W., Singh S., Nelson C.A., Kanner R., Bencosme Y., Lee Y.K., Hauser S.L., et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc. Natl. Acad. Sci. USA. 2017;114:10713–10718. doi: 10.1073/pnas.1711235114. PubMed DOI PMC

Medel-Matus J.-S., Shin D., Dorfman E., Sankar R., Mazarati A. Facilitation of kindling epileptogenesis by chronic stress may be mediated by intestinal microbiome. Epilepsia Open. 2018;3:290–294. doi: 10.1002/epi4.12114. PubMed DOI PMC

Molina-Torres G., Rodriguez-Arrastia M., Roman P., Sanchez-Labraca N., Cardona D. Stress and the gut microbiota-brain axis. Behav. Pharmacol. 2019;30:187–200. doi: 10.1097/FBP.0000000000000478. PubMed DOI

De Caro C., Leo A., Nesci V., Ghelardini C., di Cesare Mannelli L., Striano P., Avagliano C., Calignano A., Mainardi P., Constanti A., et al. Intestinal inflammation increases convulsant activity and reduces antiepileptic drug efficacy in a mouse model of epilepsy. Sci. Rep. 2019;9:13983. doi: 10.1038/s41598-019-50542-0. PubMed DOI PMC

Tang A.T., Choi J.P., Kotzin J.J., Yang Y., Hong C.C., Hobson N., Girard R., Zeineddine H.A., Lightle R., Moore T., et al. Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature. 2017;545:305–310. doi: 10.1038/nature22075. PubMed DOI PMC

Gong X., Liu X., Chen C., Lin J., Li A., Guo K., An D., Zhou D., Hong Z. Alteration of Gut Microbiota in Patients With Epilepsy and the Potential Index as a Biomarker. Front. Microbiol. 2020;11:11. doi: 10.3389/fmicb.2020.517797. PubMed DOI PMC

Peng A., Qiu X., Lai W., Li W., Zhang L., Zhu X., He S., Duan J., Chen L. Altered composition of the gut microbiome in patients with drug-resistant epilepsy. Epilepsy Res. 2018;147:102–107. doi: 10.1016/j.eplepsyres.2018.09.013. PubMed DOI

Xie G., Zhou Q., Qiu C.Z., Dai W.K., Wang H.P., Li Y.H., Liao J.X., Lu X.G., Lin S.F., Ye J.H., et al. Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy. World J. Gastroenterol. 2017;23:6164–6171. doi: 10.3748/wjg.v23.i33.6164. PubMed DOI PMC

Lindefeldt M., Eng A., Darban H., Bjerkner A., Zetterström C.K., Allander T., Andersson B., Borenstein E., Dahlin M., Prast-Nielsen S. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. NPJ Biofilms Microbiomes. 2019;5:1–13. doi: 10.1038/s41522-018-0073-2. PubMed DOI PMC

Zhang Y., Zhou S., Zhou Y., Yu L., Zhang L., Wang Y. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Res. 2018;145:163–168. doi: 10.1016/j.eplepsyres.2018.06.015. PubMed DOI

Chatzikonstantinou S., Gioula G., Kimiskidis V.K., McKenna J., Mavroudis I., Kazis D. The gut microbiome in drug-resistant epilepsy. Epilepsia Open. 2021;6:28–37. doi: 10.1002/epi4.12461. PubMed DOI PMC

Scharfman H.E. The neurobiology of epilepsy. Curr. Neurol. Neurosci. Rep. 2007;7:348–354. doi: 10.1007/s11910-007-0053-z. PubMed DOI PMC

Guerriero R.M., Giza C.C., Rotenberg A. Glutamate and GABA Imbalance Following Traumatic Brain Injury. Curr. Neurol. Neurosci. Rep. 2015;15:27. doi: 10.1007/s11910-015-0545-1. PubMed DOI PMC

Pitkänen A., Lukasiuk K., Dudek F.E., Staley K.J. Epileptogenesis. Cold Spring Harb. Perspect. Med. 2015;5:a022822. doi: 10.1101/cshperspect.a022822. PubMed DOI PMC

Rana A., Musto A.E. The role of inflammation in the development of epilepsy. J. Neuroinflamm. 2018;15:144. doi: 10.1186/s12974-018-1192-7. PubMed DOI PMC

Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018;1693:128–133. doi: 10.1016/j.brainres.2018.03.015. PubMed DOI PMC

Bagdy G., Kecskemeti V., Riba P., Jakus R. Serotonin and epilepsy. J. Neurochem. 2007;100:857–873. doi: 10.1111/j.1471-4159.2006.04277.x. PubMed DOI

Casillas-Espinosa P.M., Powell K.L., O’Brien T.J. Regulators of synaptic transmission: Roles in the pathogenesis and treatment of epilepsy. Epilepsia. 2012;53:41–58. doi: 10.1111/epi.12034. PubMed DOI

Lim J.S., Lim M.Y., Choi Y., Ko G. Modeling environmental risk factors of autism in mice induces IBD-related gut microbial dysbiosis and hyperserotonemia. Mol. Brain. 2017;10:14. doi: 10.1186/s13041-017-0292-0. PubMed DOI PMC

Lee K., Kim N., Shim J.O., Kim G.-H. Gut Bacterial Dysbiosis in Children with Intractable Epilepsy. J. Clin. Med. 2020;10:5. doi: 10.3390/jcm10010005. PubMed DOI PMC

Arulsamy A., Tan Q.Y., Balasubramaniam V., O’Brien T.J., Shaikh M.F. Gut Microbiota and Epilepsy: A Systematic Review on Their Relationship and Possible Therapeutics. ACS Chem. Neurosci. 2020;11:3488–3498. doi: 10.1021/acschemneuro.0c00431. PubMed DOI

Bravo J.A., Forsythe P., Chew M.V., Escaravage E., Savignac H.M., Dinan T.G., Bienenstock J., Cryan J.F. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. USA. 2011;108:16050–16055. doi: 10.1073/pnas.1102999108. PubMed DOI PMC

Bagheri S., Heydari A., Alinaghipour A., Salami M. Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ-induced chemical kindling. Epilepsy Behav. 2019;95:43–50. doi: 10.1016/j.yebeh.2019.03.038. PubMed DOI

Gómez-Eguílaz M., Ramón-Trapero J.L., Pérez-Martínez L., Blanco J.R. The beneficial effect of probiotics as a supplementary treatment in drug-resistant epilepsy: A pilot study. Benef. Microbes. 2018;9:875–881. doi: 10.3920/BM2018.0018. PubMed DOI

Sutter R., Rüegg S., Tschudin-Sutter S. Seizures as adverse events of antibiotic drugs. Neurology. 2015;85:1332–1341. doi: 10.1212/WNL.0000000000002023. PubMed DOI

Braakman H.M.H., van Ingen J. Can epilepsy be treated by antibiotics? J. Neurol. 2018;265:1934–1936. doi: 10.1007/s00415-018-8943-3. PubMed DOI

Wang D.D., Englot D.J., Garcia P.A., Lawton M.T., Young W.L. Minocycline- and tetracycline-class antibiotics are protective against partial seizures in vivo. Epilepsy Behav. 2012;24:314–318. doi: 10.1016/j.yebeh.2012.03.035. PubMed DOI PMC

Ianiro G., Tilg H., Gasbarrini A. Antibiotics as deep modulators of gut microbiota: Between good and evil. Gut. 2016;65:1906–1915. doi: 10.1136/gutjnl-2016-312297. PubMed DOI

Jakobsson H.E., Jernberg C., Andersson A.F., Sjölund-Karlsson M., Jansson J.K., Engstrand L. Short-term antibiotic treatment has differing long- term impacts on the human throat and gut microbiome. PLoS ONE. 2010;5:e9836. doi: 10.1371/journal.pone.0009836. PubMed DOI PMC

Maurice C.F., Haiser H.J., Turnbaugh P.J. Xenobiotics Shape the Physiology and Gene Expression of the Active Human Gut Microbiome. Cell. 2013;152:39–50. doi: 10.1016/j.cell.2012.10.052. PubMed DOI PMC

Wolf S.A., Mattei D. You Need Guts to Make New Neurons. Curr. Behav. Neurosci. Rep. 2017;4:353–360. doi: 10.1007/s40473-017-0127-4. DOI

Akbari E., Asemi Z., Kakhaki R.D., Bahmani F., Kouchaki E., Tamtaji O.R., Hamidi G.A., Salami M. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer’s disease: A randomized, double-blind and controlled trial. Front. Aging Neurosci. 2016;8:256. doi: 10.3389/fnagi.2016.00256. PubMed DOI PMC

Lv T., Ye M., Luo F., Hu B., Wang A., Chen J., Yan J., He Z., Chen F., Qian C., et al. Probiotics treatment improves cognitive impairment in patients and animals: A systematic review and meta-analysis. Neurosci. Biobehav. Rev. 2021;120:159–172. doi: 10.1016/j.neubiorev.2020.10.027. PubMed DOI

Lu K., Mahbub R., Fox J.G. Xenobiotics: Interaction with the Intestinal Microflora. ILAR J. 2015;56:218–227. doi: 10.1093/ilar/ilv018. PubMed DOI PMC

Wanleenuwat P., Suntharampillai N., Iwanowski P. Antibiotic-induced epileptic seizures: Mechanisms of action and clinical considerations. Seizure. 2020;81:167–174. doi: 10.1016/j.seizure.2020.08.012. PubMed DOI

Esposito S., Canevini M.P., Principi N. Complications associated with antibiotic administration: Neurological adverse events and interference with antiepileptic drugs. Int. J. Antimicrob. Agents. 2017;50:1–8. doi: 10.1016/j.ijantimicag.2017.01.027. PubMed DOI

Wang Y.-F., Qiao M., Zhu D., Zhu Y.-G. Antibiotic Resistance in the Collembolan Gut Microbiome Accelerated by the Nonantibiotic Drug Carbamazepine. Environ. Sci. Technol. 2020;54:10754–10762. doi: 10.1021/acs.est.0c03075. PubMed DOI

Stokes J.M., Davis J.H., Mangat C.S., Williamson J.R., Brown E.D. Discovery of a small molecule that inhibits bacterial ribosome biogenesis. eLife. 2014;3:e03574. doi: 10.7554/eLife.03574. PubMed DOI PMC

Cussotto S., Strain C.R., Fouhy F., Strain R.G., Peterson V.L., Clarke G., Stanton C., Dinan T.G., Cryan J.F. Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function. Psychopharmacology. 2019;236:1671–1685. doi: 10.1007/s00213-018-5006-5. PubMed DOI

Liu F., Horton-Sparks K., Hull V., Li R.W., Martínez-Cerdeño V. The valproic acid rat model of autism presents with gut bacterial dysbiosis similar to that in human autism. Mol. Autism. 2018;9:61. doi: 10.1186/s13229-018-0251-3. PubMed DOI PMC

Sgritta M., Dooling S.W., Buffington S.A., Momin E.N., Francis M.B., Britton R.A., Costa-Mattioli M. Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder. Neuron. 2019;101:246–259.e6. doi: 10.1016/j.neuron.2018.11.018. PubMed DOI PMC

Zimmermann M., Zimmermann-Kogadeeva M., Wegmann R., Goodman A.L. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science. 2019;363:eaat9931. doi: 10.1126/science.aat9931. PubMed DOI PMC

Clarke G., Sandhu K.V., Griffin B.T., Dinan T.G., Cryan J.F., Hyland N.P. Gut Reactions: Breaking Down Xenobiotic–Microbiome Interactions. Pharmacol. Rev. 2019;71:198–224. doi: 10.1124/pr.118.015768. PubMed DOI

Javdan B., Lopez J.G., Chankhamjon P., Lee Y.-C.J., Hull R., Wu Q., Wang X., Chatterjee S., Donia M.S. Personalized Mapping of Drug Metabolism by the Human Gut Microbiome. Cell. 2020;181:1661–1679.e22. doi: 10.1016/j.cell.2020.05.001. PubMed DOI PMC

Kitamura S., Sugihara K., Kuwasako M., Tatsumi K. The role of mammalian intestinal bacteria in the reductive metabolism of zonisamide. J. Pharm. Pharmacol. 1997;49:253–256. doi: 10.1111/j.2042-7158.1997.tb06790.x. PubMed DOI

Ułamek-Kozioł M., Czuczwar S.J., Januszewski S., Pluta R. Ketogenic Diet and Epilepsy. Nutrients. 2019;11:2510. doi: 10.3390/nu11102510. PubMed DOI PMC

Fan Y., Wang H., Liu X., Zhang J., Liu G. Crosstalk between the Ketogenic Diet and Epilepsy: From the Perspective of Gut Microbiota. Mediat. Inflamm. 2019;2019:1–9. doi: 10.1155/2019/8373060. PubMed DOI PMC

Paoli A., Mancin L., Bianco A., Thomas E., Mota J.F., Piccini F. Ketogenic diet and microbiota: Friends or enemies? Genes. 2019;10:534. doi: 10.3390/genes10070534. PubMed DOI PMC

Olson C.A., Vuong H.E., Yano J.M., Liang Q.Y., Nusbaum D.J., Hsiao E.Y. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell. 2018;173:1728–1741.e13. doi: 10.1016/j.cell.2018.04.027. PubMed DOI PMC

Spinelli E., Blackford R. Gut Microbiota, the Ketogenic Diet and Epilepsy. Pediatr. Neurol. Briefs. 2018;32:10. doi: 10.15844/pedneurbriefs-32-10. PubMed DOI PMC

Eor J.Y., Tan P.L., Son Y.J., Kwak M.J., Kim S.H. 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. doi: 10.1016/j.eplepsyres.2020.106506. PubMed DOI

Yeom J.S., Park J.S., Kim Y.-S., Kim R.B., Choi D.-S., Chung J.-Y., Han T.-H., Seo J.-H., Park E.S., Lim J.-Y., et al. Neonatal seizures and white matter injury: Role of rotavirus infection and probiotics. Brain Dev. 2019;41:19–28. doi: 10.1016/j.braindev.2018.07.001. PubMed DOI

He Z., Cui B.-T., Zhang T., Li P., Long C.-Y., Ji G.-Z., Zhang F.-M. Fecal microbiota transplantation cured epilepsy in a case with Crohn’s disease: The first report. World J. Gastroenterol. 2017;23:3565. doi: 10.3748/wjg.v23.i19.3565. PubMed DOI PMC

Allen J.M., Mailing L.J., Cohrs J., Salmonson C., Fryer J.D., Nehra V., Hale V.L., Kashyap P., White B.A., Woods J.A. Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice. Gut Microbes. 2018;9:115–130. doi: 10.1080/19490976.2017.1372077. PubMed DOI PMC

Allen J.M., Berg Miller M.E., Pence B.D., Whitlock K., Nehra V., Gaskins H.R., White B.A., Fryer J.D., Woods J.A. Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice. J. Appl. Physiol. 2015;118:1059–1066. doi: 10.1152/japplphysiol.01077.2014. PubMed DOI

Clarke S.F., Murphy E.F., O’Sullivan O., Lucey A.J., Humphreys M., Hogan A., Hayes P., O’Reilly M., Jeffery I.B., Wood-Martin R., et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014;63:1913–1920. doi: 10.1136/gutjnl-2013-306541. PubMed DOI

Mach N., Fuster-Botella D. Endurance exercise and gut microbiota: A review. J. Sport Health Sci. 2017;6:179–197. doi: 10.1016/j.jshs.2016.05.001. PubMed DOI PMC

Pimentel J., Tojal R., Morgado J. Epilepsy and physical exercise. Seizure. 2015;25:87–94. doi: 10.1016/j.seizure.2014.09.015. PubMed DOI

Arida R.M. Physical exercise and seizure activity. Biochim. Biophys. Acta Mol. Basis Dis. 2021;1867:165979. doi: 10.1016/j.bbadis.2020.165979. PubMed DOI

Eriksen H.R., Ellertsen B., Gronningsaeter H., Nakken K.O., Loyning Y., Ursin H. Physical Exercise in Women with Intractable Epilepsy. Epilepsia. 1994;35:1256–1264. doi: 10.1111/j.1528-1157.1994.tb01797.x. PubMed DOI

Nakken K.O., Bjørholt P.G., Johannessen S.I., LoSyning T., Lind E. Effect of Physical Training on Aerobic Capacity, Seizure Occurrence, and Serum Level of Antiepileptic Drugs in Adults with Epilepsy. Epilepsia. 1990;31:88–94. doi: 10.1111/j.1528-1157.1990.tb05365.x. PubMed DOI

McAuley J.W., Long L., Heise J., Kirby T., Buckworth J., Pitt C., Lehman K.J., Moore J.L., Reeves A.L. A Prospective Evaluation of the Effects of a 12-Week Outpatient Exercise Program on Clinical and Behavioral Outcomes in Patients with Epilepsy. Epilepsy Behav. 2001;2:592–600. doi: 10.1006/ebeh.2001.0271. PubMed DOI

Götze W., Kubicki S., Munter M., Teichmann J. Effect of physical exercise on seizure threshold (investigated by electroencephalographic telemetry) Dis. Nerv. Syst. 1967;28:664–667. PubMed

Aird R.B. The Importance of Seizure-Inducing Factors in the Control of Refractory Forms of Epilepsy. Epilepsia. 1983;24:567–583. doi: 10.1111/j.1528-1157.1983.tb03421.x. PubMed DOI

Sheng J., Liu S., Qin H., Li B., Zhang X. Drug-Resistant Epilepsy and Surgery. Curr. Neuropharmacol. 2017;16:17–28. doi: 10.2174/1570159X15666170504123316. PubMed DOI PMC

Chen B., Choi H., Hirsch L.J., Katz A., Legge A., Buchsbaum R., Detyniecki K. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav. 2017;76:24–31. doi: 10.1016/j.yebeh.2017.08.039. PubMed DOI

Thambi M., Nathan J., Radhakrishnan K. Can change in gut microbiota composition be used as a surrogate marker of treatment efficacy of ketogenic diet in patients with drug-resistant epilepsy? Epilepsy Behav. 2020;113:107444. doi: 10.1016/j.yebeh.2020.107444. PubMed DOI

Iannone L.F., Gómez-Eguílaz M., Citaro R., Russo E. The potential role of interventions impacting on gut-microbiota in epilepsy. Expert Rev. Clin. Pharmacol. 2020;13:423–435. doi: 10.1080/17512433.2020.1759414. PubMed DOI

De Caro C., Iannone L.F., Citraro R., Striano P., De Sarro G., Constanti A., Cryan J.F., Russo E. Can we ‘seize’ the gut microbiota to treat epilepsy? Neurosci. Biobehav. Rev. 2019;107:750–764. doi: 10.1016/j.neubiorev.2019.10.002. PubMed DOI