The Gut Microbiota in Epilepsy: Current Concepts of Mechanisms and Potential Therapeutics



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Submitted Jan 14, 2022
Published Feb 8, 2022
10.24018/ejbio.2022.3.1.331

Abstract viewed = 330 times

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Epilepsy is a non-communicable brain disorder characterized by an individual's proclivity for spontaneous epileptic seizures. Epilepsy may be classified into six types: genetic, structural, metabolic, infectious, immune-related, and unexplained causes. Numerous current findings have shown evidence that an imbalance in the gut microbiota is a cause of epilepsy. Between the gut microbiota and the brain systems, there are five putative communication pathways. The neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis, intestinal bacteria's production of neurotransmitters, the intestinal immune system, and the relationship between the intestinal mucosal barrier and the blood-brain barrier are among them. Future epilepsy interventions might include modifications of antiepileptic medications, a ketogenic diet, and probiotics as a possible treatment in the gut flora. However, further research is required to assess long-term therapeutic benefits.

Keywords: Epilepsy, gut microbiota, nketogenic diet, eurological disease, probiotics

References

  1. Al-Ghezi, Z.Z., Busbee, P.B., Alghetaa, H., Nagarkatti, P.S., Nagarkatti, M. (2019). Combination of cannabinoids, delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigates experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome. Brain Behav Immun, 82, 25–35.
     Google Scholar
  2. Borghi, E., & Vignoli, A. (2019). Rett syndrome and other neurodevelopmental disorders share common changes in gut microbial community: a descriptive review. Int. J. Mol. Sci, 20, 17.
     Google Scholar
  3. Blander, J.M., Longman, R.S., Iliev, I.D., Sonnenberg, G., Artis, D. (2017). Regulation of inflammation by microbiota interactions with the host. Nat Immunol, 18, 851–60.
     Google Scholar
  4. Balosso, S., Liu, J., Bianchi, M.E., Vezzani, A. (2014). Disulfide-containing high mobility group box-1 promotes N-methyl-D-aspartate receptor function and excitotoxicity by activating toll-like receptor 4- dependent signaling in hippocampal neurons. Antioxid Redox Signal, 21, 1726–40.
     Google Scholar
  5. Bagheri, S., Heydari, A., Alinaghipour, A., Salami M. (2019). Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ induced chemical kindling. Epilepsy Behav, 95, 43–50.
     Google Scholar
  6. Cryan, J.F., O’Riordan, K.J., Sandhu, K., Peterson, V., Dinan, T.G. (2020) The gut microbiome in neurological disorders. Lancet Neurol, 19, 179–94.
     Google Scholar
  7. Calderón, N., Betancourt, L., Hernández, L., Rada, P. (2017). A ketogenic diet modifies glutamate, gammaaminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study. Neurosci. Lett, 642, 158–62.
     Google Scholar
  8. Drekonja, D., Reich, J., Gezahegn, S., Greer, N., Shaukat, A., MacDonald, R., et al. (2015). Fecal microbiota transplantation for clostridium difficile infection: a systematic review. Ann Intern Med, 162, 630–8.
     Google Scholar
  9. de Theije, C.G.M., Wopereis, H., Ramadan, M., van Eijndthoven, T., Lambert. J., Knol, J., et al. (2014). Altered gut microbiota and activity in a murine model of autism spectrum disorders. Brain Behavior Immun, 37, 197–206.
     Google Scholar
  10. Erny, D., Hrabě de Angelis, A.L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., et al. (2015). Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci, 18, 965–77.
     Google Scholar
  11. Eor, J.Y, Tan, P.L, Son, Y.J, Kwak, M.J, Kim, S.H. (2021). Gut microbiota modulation by both lactobacillus fermentum MSK 408 and ketogenic diet in a murine model of pentylenetetrazole-induced acute seizure. Epilepsy Res, 169, 106506.
     Google Scholar
  12. Fisher, R.S., Acevedo, C., Arzimanoglou, A., Bogacz, A., Cross, J.H., Elger, C.E., et al. (2014). ILAE official report: a practical clinical definition of epilepsy. Epilepsia, 55(4), 475–82.
     Google Scholar
  13. Ferraris, C., Meroni, E., Casiraghi, M.C., Tagliabue, A., De Giorgis, V., Erba, D. (2021). One month of classic therapeutic ketogenic diet decreases short chain fatty acids production in epileptic patients. Front Nutr. 2021, 8, 613100.
     Google Scholar
  14. GBD 2016 Epilepsy Collaborators. (2019) Global, regional, and national burden of epilepsy, 1990–2016: A systematic analysis for the Global Burden of Disease Study. Lancet Neurol,18, 357–75.
     Google Scholar
  15. Guzel, O., Uysal, U., Arslan, N. (2019). Efficacy and tolerability of olive oil-based ketogenic diet in children with drug-resistant epilepsy: a single center experience from turkey. Eur J Paediatr Neurol, 23, 143–51.
     Google Scholar
  16. Gómez-Eguílaz, M., Ramón-Trapero, J.L., Pérez-Martínez, L., Blanco, J.R. (2018). The beneficial effect of probiotics as a supplementary treatment in drug-resistant epilepsy: A pilot study. Benef. Microbes, 9, 875–81.
     Google Scholar
  17. He, Z., Cui, B.T., Zhang, T., Li, P., Long, C.Y., Ji, G.Z., et al. (2017). Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report.World J Gastroenterol, 21, 23(19), 3565–8.
     Google Scholar
  18. Hill, C., Guarner, F., Reid, G., Gibson, G.R., Merenstein, D.J., Pot, B., et al. (2014). Expert consensus document. the international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol, 11, 506–14.
     Google Scholar
  19. Jakobsson, H.E., Rodríguez-Piñeiro, A.M., Schütte, A., Ermund, A., Boysen, P., Bemark, M., et al. (2015). The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep, 16, 164–77.
     Google Scholar
  20. Kossoff, E.H., Zupec-Kania, B.A., Auvin, S., Ballaban-Gil, K.R., Christina, B.A.G., Blackford, R., et al. (2018). Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the international ketogenic diet study group. Epilepsia Open, 3(2), 175–92.
     Google Scholar
  21. Lambrechts, D.A.J.E., de Kinderen, R.J.A., Vles, J.S.H., de Louw, A.J.A., Aldenkamp, A.P., Majoie, H.J.M. (2017). A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy. Acta Neurol Scand, 135(2), 231–9.
     Google Scholar
  22. Mendes, V., Galvão, I., Vieira, A.T. (2019). Mechanisms by which the gut microbiota influences cytokine production and modulates host inflammatory responses. J. Interf. Cytokine Res, 39, 393–409.
     Google Scholar
  23. Mayer, E.A., Tillisch, K., Gupta, A. (2015). Gut/brain axis and the microbiota. J Clin Invest, 125(3), 926–38.
     Google Scholar
  24. Maroso, M., Balosso, S., Ravizza, T., Liu, J., Aronica, E., Iyer, A.M, et al. (2010). Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med, 16, 413–9.
     Google Scholar
  25. Maier, L., Pruteanu, M., Kuhn, M., Zeller, G., Telzerow, A., Anderson, E.E., et al. (2018). Extensive Impact of Non-Antibiotic Drugs on Human Gut Bacteria. Nature, 555, 623–8.
     Google Scholar
  26. Neal, E.G., Chaffe, H., Schwartz, R.H., Lawson, M.S., Edwards, N., Fitzsimmons, G., et al. (2008). The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol, 7(6), 500–6.
     Google Scholar
  27. O’Mahony, S.M., Clarke, G., Borre, Y.E., Dinan, T.G., Cryan, J.F. (2015). Serotonin, tryptophan metabolism and the brain-gut- microbiome axis. Behav Brain Res, 15(277), 32–48.
     Google Scholar
  28. Peng, A., Qiu, X., Lai, W., Li, W., Zhang, L., Zhu, X., et al. (2018). Altered composition of the gut microbiome in patients with drug-resistant epilepsy. Epilepsy Res, 147, 102–7.
     Google Scholar
  29. Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G., Gasbarrini, A., et al. (2019). What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms, 7, 14.
     Google Scholar
  30. Raymond, F., Ouameur, A.A., Déraspe, M., Iqbal, N., Gingras, H., Dridi, B., et al. (2016). The initial state of the human gut microbiome determines its reshaping by antibiotics. ISME J, 10, 707–20.
     Google Scholar
  31. Rogawski, M.A., Löscher, W., Rho, J.M. (2016). Mechanisms of action of antiseizure drugs and the ketogenic diet. Cold Spring Harb Perspect Med, 2, 65.
     Google Scholar
  32. Scheffer, I.E., Berkovic, S., Capovilla, G., Connolly, M.B., French, J., Guilhoto, L., et al. (2017). ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology. Epilepsia, 58(4), 512–21.
     Google Scholar
  33. Sgritta, M., Dooling, S.W., Buffington, S.A., Momin, E.N., Francis, M.B., Britton, R.A., et al. (2019). Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder. Neuron, 101, 246–59.
     Google Scholar
  34. Stokes, J.M., Davis, J.H., Mangat, C.S., Williamson, J.R., Brown, E.D. (2014). Discovery of a small molecule that inhibits bacterial ribosome biogenesis. Elife, 3, e03574.
     Google Scholar
  35. Swanson, K.S., Gibson, G.R., Hutkins, R., Reimer, R.A., Reid, G., Verbeke, K., et al. (2020). The international scientific association for probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat Rev Gastroenterol Hepatol, 17, 687–701.
     Google Scholar
  36. Ułamek-Kozioł, M., Czuczwar, S.J., Januszewski, S., Pluta, R. (2019). Ketogenic diet and epilepsy. Nutrients, 11, 2510.
     Google Scholar
  37. van de Wouw, M., Boehme, M., Lyte, J.M., Wiley, N., Strain, C., O'Sullivan, O., et al. (2018). Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations. J Physiol, 596, 4923–44.
     Google Scholar
  38. Wang, H.X., & Wang, Y.P. (2016). Gut microbiota-brain axis. Chin Med J (Engl), 129(19), 2373–80.
     Google Scholar
  39. Warner, B.B. (2019). The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders. Pediatr Res, 85(2), 216–24.
     Google Scholar
  40. Yamashiro, Y. (2017). Gut microbiota in health and disease. Ann. Nutr. Metab, 71, 242–46.
     Google Scholar
  41. Yan, F., & Polk, D.B. (2020). Probiotics and probiotic-derived functional factors- mechanistic insights into applications for intestinal homeostasis. Front Immunol, 11, 1428.
     Google Scholar
  42. Zocco, M.A., Ainora, M.E., Gasbarrini, G., Gasbarrini, A. (2007). Bacteroides thetaiotaomicron in the gut: molecular aspects of their interaction. Dig. Liver Dis, 39, 707–12.
     Google Scholar
  43. Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R., Goodman, A.L. (2019). Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science, 363.
     Google Scholar