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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

The Role of the Vagus Nerve in the Microbiome and Digestive System in Relation to Epilepsy

Author(s): Carmen Rubio, Ernesto Ochoa, Fernando Gatica, Alonso Portilla, David Vázquez and Moisés Rubio-Osornio*

Volume 31, Issue 37, 2024

Published on: 19 October, 2023

Page: [6018 - 6031] Pages: 14

DOI: 10.2174/0109298673260479231010044020

Price: $65

Abstract

The Enteric Nervous System (ENS) is described as a division of the Peripheral Nervous System (PNS), located within the gut wall and it is formed by two main plexuses: the myenteric plexus (Auerbach's) and the submucosal plexus (Meissner's). The contribution of the ENS to the pathophysiology of various neurological diseases such as Parkinson's or Alzheimer's disease has been described in the literature, while some other studies have found a connection between epilepsy and the gastrointestinal tract. The above could be explained by cholinergic neurons and neurotransmission systems in the myenteric and submucosal plexuses, regulating the vagal excitability effect. It is also understandable, as the discharges arising in the amygdala are transmitted to the intestine through projections the dorsal motor nucleus of the vagus, giving rise to efferent fibers that stimulate the gastrointestinal tract and consequently the symptoms at this level. Therefore, this review's main objective is to argue in favor of the existing relationship of the ENS with the Central Nervous System (CNS) as a facilitator of epileptogenic or ictogenic mechanisms. The gut microbiota also participates in this interaction; however, it depends on many individual factors of each human being. The link between the ENS and the CNS is a poorly studied epileptogenic site with a big impact on one of the most prevalent neurological conditions such as epilepsy.

[1]
Rao, M.; Gershon, M.D. The bowel and beyond: The enteric nervous system in neurological disorders. Nat. Rev. Gastroenterol. Hepatol., 2016, 13(9), 517-528.
[http://dx.doi.org/10.1038/nrgastro.2016.107] [PMID: 27435372]
[2]
Camilleri, M. Disorders of gastrointestinal motility in neurologic diseases. Mayo Clin. Proc., 1990, 65(6), 825-846.
[http://dx.doi.org/10.1016/S0025-6196(12)62574-9] [PMID: 2164123]
[3]
Benarroch, E.E. Enteric nervous system: Functional organization and neurologic implications. Neurology, 2007, 69(20), 1953-1957.
[http://dx.doi.org/10.1212/01.wnl.0000281999.56102.b5] [PMID: 17998487]
[4]
Horoupian, D.S.; Kim, Y. Encephalomyeloneuropathy with ganglionitis of the myenteric plexuses in the absence of cancer. Ann. Neurol., 1982, 11(6), 628-632.
[http://dx.doi.org/10.1002/ana.410110613] [PMID: 7114813]
[5]
Ghosh, S. Mechanism of intestinal entry of infectious prion protein in the pathogenesis of variant Creutzfeldt–Jakob disease. Adv. Drug Deliv. Rev., 2004, 56(6), 915-920.
[http://dx.doi.org/10.1016/j.addr.2003.10.035] [PMID: 15063598]
[6]
McElhanon, B.O.; McCracken, C.; Karpen, S.; Sharp, W.G. Gastrointestinal symptoms in autism spectrum disorder: A meta-analysis. Pediatrics, 2014, 133(5), 872-883.
[http://dx.doi.org/10.1542/peds.2013-3995] [PMID: 24777214]
[7]
Chang, L.; Wei, Y.; Hashimoto, K. Brain–gut–microbiota axis in depression: A historical overview and future directions. Brain Res. Bull., 2022, 182, 44-56.
[http://dx.doi.org/10.1016/j.brainresbull.2022.02.004] [PMID: 35151796]
[8]
Socała, K.; Doboszewska, U.; Szopa, A.; Serefko, A.; Włodarczyk, M.; Zielińska, A.; Poleszak, E.; Fichna, J.; Wlaź, P. The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders. Pharmacol. Res., 2021, 172, 105840.
[http://dx.doi.org/10.1016/j.phrs.2021.105840] [PMID: 34450312]
[9]
Stokholm, M.G.; Danielsen, E.H.; Hamilton-Dutoit, S.J.; Borghammer, P. Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. Ann. Neurol., 2016, 79(6), 940-949.
[http://dx.doi.org/10.1002/ana.24648] [PMID: 27015771]
[10]
Puig, K.L.; Lutz, B.M.; Urquhart, S.A.; Rebel, A.A.; Zhou, X.; Manocha, G.D.; Sens, M.; Tuteja, A.K.; Foster, N.L.; Combs, C.K. Overexpression of mutant amyloid-β protein precursor and presenilin 1 modulates enteric nervous system. J. Alzheimers Dis., 2015, 44(4), 1263-1278.
[http://dx.doi.org/10.3233/JAD-142259] [PMID: 25408221]
[11]
Naveed, M.; Zhou, Q.G.; Xu, C.; Taleb, A.; Meng, F.; Ahmed, B.; Zhang, Y.; Fukunaga, K.; Han, F. Gut-brain axis: A matter of concern in neuropsychiatric disorders…! Prog. Neuropsychopharmacol. Biol. Psychiatry, 2021, 104, 110051.
[http://dx.doi.org/10.1016/j.pnpbp.2020.110051] [PMID: 32758517]
[12]
Kundu, S.; Nayak, S.; Rakshit, D.; Singh, T.; Shukla, R.; Khatri, D.K.; Mishra, A. The microbiome–gut–brain axis in epilepsy: Pharmacotherapeutic target from bench evidence for potential bedside applications. Eur. J. Neurol., 2023, 2023, 15767.
[http://dx.doi.org/10.1111/ene.15767] [PMID: 36880679]
[13]
Pitkänen, A.; Lukasiuk, K.; Dudek, F.E.; Staley, K.J. Epileptogenesis. Cold Spring Harb. Perspect. Med., 2015, 5(10), a022822.
[http://dx.doi.org/10.1101/cshperspect.a022822] [PMID: 26385090]
[14]
Papathanasiou, E.S.; Pantzaris, M.; Myrianthopoulou, P.; Kkolou, E.; Papacostas, S.S. Brainstem lesions may be important in the development of epilepsy in multiple sclerosis patients: An evoked potential study. Clin. Neurophysiol., 2010, 121(12), 2104-2110.
[http://dx.doi.org/10.1016/j.clinph.2010.05.017] [PMID: 20542465]
[15]
Streng, M.L.; Krook-Magnuson, E. The cerebellum and epilepsy. Epilepsy Behav., 2021, 121(Pt B), 106909.
[http://dx.doi.org/10.1016/j.yebeh.2020.106909] [PMID: 32035793]
[16]
Cloix, J.F.; Hévor, T. Epilepsy, regulation of brain energy metabolism and neurotransmission. Curr. Med. Chem., 2009, 16(7), 841-853.
[http://dx.doi.org/10.2174/092986709787549316] [PMID: 19275597]
[17]
Avoli, M.; D’Antuono, M.; Louvel, J.; Köhling, R.; Biagini, G.; Pumain, R.; D’Arcangelo, G.; Tancredi, V. Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro. Prog. Neurobiol., 2002, 68(3), 167-207.
[http://dx.doi.org/10.1016/S0301-0082(02)00077-1] [PMID: 12450487]
[18]
Sarlo, G.L.; Holton, K.F. Brain concentrations of glutamate and GABA in human epilepsy: A review. Seizure, 2021, 91, 213-227.
[http://dx.doi.org/10.1016/j.seizure.2021.06.028] [PMID: 34233236]
[19]
Lascano, A.M.; Korff, C.M.; Picard, F. Seizures and epilepsies due to channelopathies and neurotransmitter receptor dysfunction: A parallel between genetic and immune aspects. Mol. Syndromol., 2016, 7(4), 197-209.
[http://dx.doi.org/10.1159/000447707] [PMID: 27781030]
[20]
Devinsky, O.; Vezzani, A.; Najjar, S.; De Lanerolle, N.C.; Rogawski, M.A. Glia and epilepsy: Excitability and inflammation. Trends Neurosci., 2013, 36(3), 174-184.
[http://dx.doi.org/10.1016/j.tins.2012.11.008] [PMID: 23298414]
[21]
Curia, G.; Lucchi, C.; Vinet, J.; Gualtieri, F.; Marinelli, C.; Torsello, A.; Costantino, L.; Biagini, G. Pathophysiogenesis of mesial temporal lobe epilepsy: Is prevention of damage antiepileptogenic? Curr. Med. Chem., 2014, 21(6), 663-688.
[http://dx.doi.org/10.2174/0929867320666131119152201] [PMID: 24251566]
[22]
Azevedo, F.A.C.; Carvalho, L.R.B.; Grinberg, L.T.; Farfel, J.M.; Ferretti, R.E.L.; Leite, R.E.P.; Filho, W.J.; Lent, R.; Herculano-Houzel, S. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J. Comp. Neurol., 2009, 513(5), 532-541.
[http://dx.doi.org/10.1002/cne.21974] [PMID: 19226510]
[23]
Clasadonte, J.; Haydon, P.G. Astrocytes and epilepsy. In: Jasper’s Basic Mechanisms of the Epilepsies, 4th ed.; Noebels, J.L.; Avoli, M.; Rogawski, M.A., Eds.; National Center for Biotechnology Information (US): Bethesda, MD, 2012.
[http://dx.doi.org/10.1093/med/9780199746545.003.0046]
[24]
Nikolic, L.; Shen, W.; Nobili, P.; Virenque, A.; Ulmann, L.; Audinat, E. Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity during epileptogenesis. Glia, 2018, 66(12), 2673-2683.
[http://dx.doi.org/10.1002/glia.23519] [PMID: 30394583]
[25]
Wang, G.; Wang, J.; Xin, C.; Xiao, J.; Liang, J.; Wu, X. Inflammatory response in epilepsy is mediated by glial cell gap junction pathway (Review). Mol. Med. Rep., 2021, 24(1), 493.
[http://dx.doi.org/10.3892/mmr.2021.12132] [PMID: 33955516]
[26]
Jabs, R.; Seifert, G.; Steinhäuser, C. Astrocytic function and its alteration in the epileptic brain. Epilepsia, 2008, 49(2), 3-12.
[http://dx.doi.org/10.1111/j.1528-1167.2008.01488.x] [PMID: 18226167]
[27]
Bauer, J.; Elger, C.E.; Hans, V.H.; Schramm, J.; Urbach, H.; Lassmann, H.; Bien, C.G. Astrocytes are a specific immunological target in Rasmussen’s encephalitis. Ann. Neurol., 2007, 62(1), 67-80.
[http://dx.doi.org/10.1002/ana.21148] [PMID: 17503512]
[28]
Wetherington, J.; Serrano, G.; Dingledine, R. Astrocytes in the epileptic brain. Neuron, 2008, 58(2), 168-178.
[http://dx.doi.org/10.1016/j.neuron.2008.04.002] [PMID: 18439402]
[29]
Rubio, C.; López-López, F.; Rojas-Hernández, D.; Moreno, W.; Rodríguez-Quintero, P.; Rubio-Osornio, M. Caloric restriction: Anti-inflammatory and antioxidant mechanisms against epileptic seizures. Epilepsy Res., 2022, 186, 107012.
[http://dx.doi.org/10.1016/j.eplepsyres.2022.107012] [PMID: 36027691]
[30]
Boer, K.; Spliet, W.G.M.; van Rijen, P.C.; Redeker, S.; Troost, D.; Aronica, E. Evidence of activated microglia in focal cortical dysplasia. J. Neuroimmunol., 2006, 173(1-2), 188-195.
[http://dx.doi.org/10.1016/j.jneuroim.2006.01.002] [PMID: 16483671]
[31]
Ravizza, T.; Boer, K.; Redeker, S.; Spliet, W.G.M.; van Rijen, P.C.; Troost, D.; Vezzani, A.; Aronica, E. The IL-1β system in epilepsy-associated malformations of cortical development. Neurobiol. Dis., 2006, 24(1), 128-143.
[http://dx.doi.org/10.1016/j.nbd.2006.06.003] [PMID: 16860990]
[32]
Akyuz, E.; Polat, A.K.; Eroglu, E.; Kullu, I.; Angelopoulou, E.; Paudel, Y.N. Revisiting the role of neurotransmitters in epilepsy: An updated review. Life Sci., 2021, 265, 118826.
[http://dx.doi.org/10.1016/j.lfs.2020.118826] [PMID: 33259863]
[33]
Rubio, C.; Rubio-Osornio, M.; Retana-Márquez, S.; Lopez, M.; Custodio, V.; Paz, C. In vivo experimental models of epilepsy. Cent. Nerv. Syst. Agents Med. Chem., 2010, 10(4), 298-309.
[http://dx.doi.org/10.2174/187152410793429746] [PMID: 20868357]
[34]
Sibarov, D.A.; Antonov, S.M. Calcium-dependent desensitization of NMDA receptors. Biochemistry, 2018, 83(10), 1173-1183.
[http://dx.doi.org/10.1134/S0006297918100036] [PMID: 30472955]
[35]
Conn, P.J.; Pin, J.P. Pharmacology and functions of metabotropic glutamate receptors. Annu. Rev. Pharmacol. Toxicol., 1997, 37(1), 205-237.
[http://dx.doi.org/10.1146/annurev.pharmtox.37.1.205] [PMID: 9131252]
[36]
Tanaka, K.; Watase, K.; Manabe, T.; Yamada, K.; Watanabe, M.; Takahashi, K.; Iwama, H.; Nishikawa, T.; Ichihara, N.; Kikuchi, T.; Okuyama, S.; Kawashima, N.; Hori, S.; Takimoto, M.; Wada, K. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science, 1997, 276(5319), 1699-1702.
[http://dx.doi.org/10.1126/science.276.5319.1699] [PMID: 9180080]
[37]
Mahmoud, S.; Gharagozloo, M.; Simard, C.; Gris, D. Astrocytes maintain glutamate homeostasis in the CNS by controlling the balance between glutamate uptake and release. Cells, 2019, 8(2), 184.
[http://dx.doi.org/10.3390/cells8020184] [PMID: 30791579]
[38]
Schousboe, A.; Barker-Haliski, M.; Steve White, H. Modulation of excitability via glutamate and gaba transporters. Curated Ref. Collect Neurosci. Biobehav. Psychol., 2018, 397-401.
[http://dx.doi.org/10.1016/B978-0-12-809324-5.22709-0]
[39]
Lorigados, L.; Orozco, S.; Morales, L.; Estupiñán, B.; García, I.; Rocha, L. Excitotoxicidad y muerte neuronal en la epilepsia. Biotecnol. Apl., 2013, 30, 1-8.
[40]
Shih, A.Y.; Erb, H.; Sun, X.; Toda, S.; Kalivas, P.W.; Murphy, T.H. Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. J. Neurosci., 2006, 26(41), 10514-10523.
[http://dx.doi.org/10.1523/JNEUROSCI.3178-06.2006] [PMID: 17035536]
[41]
Liang, L.P.; Patel, M. Plasma cysteine/cystine redox couple disruption in animal models of temporal lobe epilepsy. Redox Biol., 2016, 9, 45-49.
[http://dx.doi.org/10.1016/j.redox.2016.05.004] [PMID: 27285054]
[42]
Uttara, B.; Singh, A.; Zamboni, P.; Mahajan, R. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
[http://dx.doi.org/10.2174/157015909787602823] [PMID: 19721819]
[43]
Pearson-Smith, J.; Patel, M. Metabolic dysfunction and oxidative stress in epilepsy. Int. J. Mol. Sci., 2017, 18(11), 2365.
[http://dx.doi.org/10.3390/ijms18112365] [PMID: 29117123]
[44]
Vezzani, A.; French, J.; Bartfai, T.; Baram, T.Z. The role of inflammation in epilepsy. Nat. Rev. Neurol., 2011, 7(1), 31-40.
[http://dx.doi.org/10.1038/nrneurol.2010.178] [PMID: 21135885]
[45]
Iori, V.; Frigerio, F.; Vezzani, A. Modulation of neuronal excitability by immune mediators in epilepsy. Curr. Opin. Pharmacol., 2016, 26, 118-123.
[http://dx.doi.org/10.1016/j.coph.2015.11.002] [PMID: 26629681]
[46]
Galic, M.A.; Riazi, K.; Pittman, Q.J. Cytokines and brain excitability. Front. Neuroendocrinol., 2012, 33(1), 116-125.
[http://dx.doi.org/10.1016/j.yfrne.2011.12.002] [PMID: 22214786]
[47]
Bradford, H.F. Glutamate, GABA and epilepsy. Prog. Neurobiol., 1995, 47(6), 477-511.
[http://dx.doi.org/10.1016/0301-0082(95)00030-5] [PMID: 8787032]
[48]
Guerriero, R.M.; Giza, C.C.; Rotenberg, A. Glutamate and GABA imbalance following traumatic brain injury. Curr. Neurol. Neurosci. Rep., 2015, 15(5), 27.
[http://dx.doi.org/10.1007/s11910-015-0545-1] [PMID: 25796572]
[49]
Devinsky, O.; Vezzani, A.; O’Brien, T.J.; Jette, N.; Scheffer, I.E.; de Curtis, M.; Perucca, P. Epilepsy. Nat. Rev. Dis. Primers, 2018, 4(1), 18024.
[http://dx.doi.org/10.1038/nrdp.2018.24] [PMID: 29722352]
[50]
Furness, J.B.; Callaghan, B.P.; Rivera, L.R.; Cho, H.J. The enteric nervous system and gastrointestinal innervation: Integrated local and central control. Adv. Exp. Med. Biol., 2014, 817, 39-71.
[http://dx.doi.org/10.1007/978-1-4939-0897-4_3] [PMID: 24997029]
[51]
Herculano-Houzel, S. The human brain in numbers: A linearly scaled-up primate brain. Front. Hum. Neurosci., 2009, 3, 31.
[http://dx.doi.org/10.3389/neuro.09.031.2009] [PMID: 19915731]
[52]
Furness, J.B.; Rivera, L.R.; Cho, H.J.; Bravo, D.M.; Callaghan, B. The gut as a sensory organ. Nat. Rev. Gastroenterol. Hepatol., 2013, 10(12), 729-740.
[http://dx.doi.org/10.1038/nrgastro.2013.180] [PMID: 24061204]
[53]
Furness, J.B. The enteric nervous system and neurogastroenterology. Nat. Rev. Gastroenterol. Hepatol., 2012, 9(5), 286-294.
[http://dx.doi.org/10.1038/nrgastro.2012.32] [PMID: 22392290]
[54]
Yoo, B.B.; Mazmanian, S.K. The enteric network: Interactions between the immune and nervous systems of the Gut. Immunity, 2017, 46(6), 910-926.
[http://dx.doi.org/10.1016/j.immuni.2017.05.011] [PMID: 28636959]
[55]
Spencer, N.J.; Hu, H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat. Rev. Gastroenterol. Hepatol., 2020, 17(6), 338-351.
[http://dx.doi.org/10.1038/s41575-020-0271-2] [PMID: 32152479]
[56]
Ren, J.; Hu, H-Z.; Liu, S.; Xia, Y.; Wood, J.D. Glutamate receptors in the enteric nervous system: Ionotropic or metabotropic? Neurogastroenterol. Motil., 2000, 12(3), 257-264.
[http://dx.doi.org/10.1046/j.1365-2982.2000.00207.x] [PMID: 10867623]
[57]
Liu, M.T.; Rothstein, J.D.; Gershon, M.D.; Kirchgessner, A.L. Glutamatergic enteric neurons. J. Neurosci., 1997, 17(12), 4764-4784.
[http://dx.doi.org/10.1523/JNEUROSCI.17-12-04764.1997] [PMID: 9169536]
[58]
Giaroni, C.; Zanetti, E.; Chiaravalli, A.M.; Albarello, L.; Dominioni, L.; Capella, C.; Lecchini, S.; Frigo, G. Evidence for a glutamatergic modulation of the cholinergic function in the human enteric nervous system via NMDA receptors. Eur. J. Pharmacol., 2003, 476(1-2), 63-69.
[http://dx.doi.org/10.1016/S0014-2999(03)02147-2] [PMID: 12969750]
[59]
Wiley, J.W.; Lu, Y.X.; Owyang, C. Evidence for a glutamatergic neural pathway in the myenteric plexus. Am. J. Physiol., 1991, 261(4 Pt 1), G693-G700.
[PMID: 1681738]
[60]
Gwynne, R.; Bornstein, J. Synaptic transmission at functionally identified synapses in the enteric nervous system: Roles for both ionotropic and metabotropic receptors. Curr. Neuropharmacol., 2007, 5(1), 1-17.
[http://dx.doi.org/10.2174/157015907780077141] [PMID: 18615154]
[61]
Kirchgessner, A.L.; Liu, M.T.; Alcantara, F. Excitotoxicity in the enteric nervous system. J. Neurosci., 1997, 17(22), 8804-8816.
[http://dx.doi.org/10.1523/JNEUROSCI.17-22-08804.1997] [PMID: 9348349]
[62]
Beyak, M.J. Visceral afferents - Determinants and modulation of excitability. Auton. Neurosci., 2010, 153(1-2), 69-78.
[http://dx.doi.org/10.1016/j.autneu.2009.07.019] [PMID: 19674942]
[63]
rühl Glial cells in the gut. Neurogastroenterol. Motil., 2005, 17(6), 777-790.
[http://dx.doi.org/10.1111/j.1365-2982.2005.00687.x] [PMID: 16336493]
[64]
Obrenovitch, T.P.; Urenjak, J. Altered glutamatergic transmission in neurological disorders: From high extracellular glutamate to excessive synaptic efficacy. Prog. Neurobiol., 1997, 51(1), 39-87.
[http://dx.doi.org/10.1016/S0301-0082(96)00049-4] [PMID: 9044428]
[65]
Bornstein, J.C.; Costa, M.; Furness, J.B. Synaptic inputs to immunohistochemically identified neurones in the submucous plexus of the guinea-pig small intestine. J. Physiol., 1986, 381(1), 465-482.
[http://dx.doi.org/10.1113/jphysiol.1986.sp016339] [PMID: 3305874]
[66]
Koussoulas, K.; Swaminathan, M.; Fung, C.; Bornstein, J.C.; Foong, J.P.P. Neurally released GABA acts via GABAC receptors to modulate Ca2+ transients evoked by trains of synaptic inputs, but not responses evoked by single stimuli, in myenteric neurons of mouse ileum. Front. Physiol., 2018, 9, 97.
[http://dx.doi.org/10.3389/fphys.2018.00097] [PMID: 29487540]
[67]
Jessen, K.R.; Mirsky, R.; Hills, J.M. GABA as an autonomic neurotransmitter: Studies on intrinsic GABAergic neurons in the myenteric plexus of the gut. Trends Neurosci., 1987, 10(6), 255-262.
[http://dx.doi.org/10.1016/0166-2236(87)90169-X]
[68]
Krantis, A. GABA in the mammalian enteric nervous system. Physiology, 2000, 15(6), 284-290.
[http://dx.doi.org/10.1152/physiologyonline.2000.15.6.284] [PMID: 11390928]
[69]
Mayer, E.A.; Knight, R.; Mazmanian, S.K.; Cryan, J.F.; Tillisch, K. Gut microbes and the brain: Paradigm shift in neuroscience. J. Neurosci., 2014, 34(46), 15490-15496.
[http://dx.doi.org/10.1523/JNEUROSCI.3299-14.2014] [PMID: 25392516]
[70]
Mitrea, L.; Nemeş, S.A.; Szabo, K.; Teleky, B.E.; Vodnar, D.C. Guts imbalance imbalances the brain: A review of gut microbiota association with neurological and psychiatric disorders. Front. Med., 2022, 9, 813204.
[http://dx.doi.org/10.3389/fmed.2022.813204] [PMID: 35433746]
[71]
Ding, M.; Lang, Y.; Shu, H.; Shao, J.; Cui, L. Microbiota-gut-brain axis and epilepsy: A review on mechanisms and potential therapeutics. Front. Immunol., 2021, 12, 742449.
[http://dx.doi.org/10.3389/fimmu.2021.742449] [PMID: 34707612]
[72]
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.
[http://dx.doi.org/10.1016/j.eplepsyres.2018.09.013] [PMID: 30291996]
[73]
Lum, G.R.; Olson, C.A.; Hsiao, E.Y. Emerging roles for the intestinal microbiome in epilepsy. Neurobiol. Dis., 2020, 135, 104576.
[http://dx.doi.org/10.1016/j.nbd.2019.104576] [PMID: 31445165]
[74]
McCoy, K.D.; Ronchi, F.; Geuking, M.B. Host-microbiota interactions and adaptive immunity. Immunol. Rev., 2017, 279(1), 63-69.
[http://dx.doi.org/10.1111/imr.12575] [PMID: 28856735]
[75]
Ceccarani, C.; Viganò, I.; Ottaviano, E.; Redaelli, M.G.; Severgnini, M.; Vignoli, A.; Borghi, E. Is gut microbiota a key player in epilepsy onset? A longitudinal study in drug-naive children. Front. Cell. Infect. Microbiol., 2021, 11, 749509.
[http://dx.doi.org/10.3389/fcimb.2021.749509] [PMID: 34926315]
[76]
Li, L.; Acioglu, C.; Heary, R.F.; Elkabes, S. Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases. Brain Behav. Immun., 2021, 91, 740-755.
[http://dx.doi.org/10.1016/j.bbi.2020.10.007] [PMID: 33039660]
[77]
De Caro, C.; Leo, A.; Nesci, V.; Ghelardini, C.; di Cesare Mannelli, L.; Striano, P.; Avagliano, C.; Calignano, A.; Mainardi, P.; Constanti, A.; Citraro, R.; De Sarro, G.; Russo, E. Intestinal inflammation increases convulsant activity and reduces antiepileptic drug efficacy in a mouse model of epilepsy. Sci. Rep., 2019, 9(1), 13983.
[http://dx.doi.org/10.1038/s41598-019-50542-0] [PMID: 31562378]
[78]
Matin, N.; Tabatabaie, O.; Falsaperla, R.; Lubrano, R.; Pavone, P.; Mahmood, F.; Gullotta, M.; Serra, A.; Mauro, P.D.; Cocuzza, S.; Vitaliti, G. Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications. Hum. Vaccin. Immunother., 2015, 11(8), 2021-2029.
[http://dx.doi.org/10.1080/21645515.2015.1034921] [PMID: 26260962]
[79]
Dicks, L.M.T. Gut bacteria and neurotransmitters. Microorganisms, 2022, 10(9), 1838.
[http://dx.doi.org/10.3390/microorganisms10091838] [PMID: 36144440]
[80]
Strandwitz, P. Neurotransmitter modulation by the gut microbiota. Brain Res., 2018, 1693((Pt B)), 128-133.
[http://dx.doi.org/10.1016/j.brainres.2018.03.015]
[81]
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(7), 1661-1679.e22.
[http://dx.doi.org/10.1016/j.cell.2020.05.001] [PMID: 32526207]
[82]
Sorboni, S.G.; Moghaddam, H.S.; Jafarzadeh-Esfehani, R.; Soleimanpour, S. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin. Microbiol. Rev., 2022, 35(1), e00338-20.
[http://dx.doi.org/10.1128/CMR.00338-20] [PMID: 34985325]
[83]
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.
[http://dx.doi.org/10.1016/j.eplepsyres.2018.06.015] [PMID: 30007242]
[84]
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(7), 1728-1741.e13.
[http://dx.doi.org/10.1016/j.cell.2018.04.027] [PMID: 29804833]
[85]
Makievskaya, C.I.; Popkov, V.A.; Andrianova, N.V.; Liao, X.; Zorov, D.B.; Plotnikov, E.Y. Ketogenic diet and ketone bodies against ischemic injury: targets, mechanisms, and therapeutic potential. Int. J. Mol. Sci., 2023, 24(3), 2576.
[http://dx.doi.org/10.3390/ijms24032576] [PMID: 36768899]
[86]
Rubio, C.; Luna, R.; Rosiles, A.; Rubio-Osornio, M. Caloric restriction and ketogenic diet therapy for epilepsy: A molecular approach involving Wnt pathway and KATP channels. Front. Neurol., 2020, 11, 584298.
[http://dx.doi.org/10.3389/fneur.2020.584298] [PMID: 33250850]
[87]
Dahlin, M.; Prast-Nielsen, S. The gut microbiome and epilepsy. EBioMedicine, 2019, 44, 741-746.
[http://dx.doi.org/10.1016/j.ebiom.2019.05.024] [PMID: 31160269]
[88]
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.
[http://dx.doi.org/10.1016/j.yebeh.2019.03.038] [PMID: 31026781]
[89]
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(3), e9836.
[http://dx.doi.org/10.1371/journal.pone.0009836] [PMID: 20352091]
[90]
Vrieze, A.; Out, C.; Fuentes, S.; Jonker, L.; Reuling, I.; Kootte, R.S.; van Nood, E.; Holleman, F.; Knaapen, M.; Romijn, J.A.; Soeters, M.R.; Blaak, E.E.; Dallinga-Thie, G.M.; Reijnders, D.; Ackermans, M.T.; Serlie, M.J.; Knop, F.K.; Holst, J.J.; van der Ley, C.; Kema, I.P.; Zoetendal, E.G.; de Vos, W.M.; Hoekstra, J.B.L.; Stroes, E.S.; Groen, A.K.; Nieuwdorp, M. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J. Hepatol., 2014, 60(4), 824-831.
[http://dx.doi.org/10.1016/j.jhep.2013.11.034] [PMID: 24316517]
[91]
Imani, S.; Buscher, H.; Marriott, D.; Gentili, S.; Sandaradura, I. Too much of a good thing: A retrospective study of β-lactam concentration–toxicity relationships. J. Antimicrob. Chemother., 2017, 72(10), 2891-2897.
[http://dx.doi.org/10.1093/jac/dkx209] [PMID: 29091190]
[92]
Kitamura, S.; Sugihara, K.; Kuwasako, M.; Tatsumi, K. The role of mammalian intestinal bacteria in the reductive metabolism of zonisamide. J. Pharm. Pharmacol., 2011, 49(3), 253-256.
[http://dx.doi.org/10.1111/j.2042-7158.1997.tb06790.x] [PMID: 9231340]
[93]
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.
[http://dx.doi.org/10.7554/eLife.03574] [PMID: 25233066]
[94]
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(2), 290-294.
[http://dx.doi.org/10.1002/epi4.12114] [PMID: 29881810]
[95]
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.
[http://dx.doi.org/10.1016/j.neubiorev.2019.10.002] [PMID: 31626816]
[96]
Brookes, S.J.H.; Spencer, N.J.; Costa, M.; Zagorodnyuk, V.P. Extrinsic primary afferent signalling in the gut. Nat. Rev. Gastroenterol. Hepatol., 2013, 10(5), 286-296.
[http://dx.doi.org/10.1038/nrgastro.2013.29] [PMID: 23438947]
[97]
Mengoni, F.; Salari, V.; Kosenkova, I.; Tsenov, G.; Donadelli, M.; Malerba, G.; Bertini, G.; Del Gallo, F.; Fabene, P.F. Gut microbiota modulates seizure susceptibility. Epilepsia, 2021, 62(9), e153-e157.
[http://dx.doi.org/10.1111/epi.17009] [PMID: 34324703]
[98]
Zubareva, O.E.; Dyomina, A.V.; Kovalenko, A.A.; Roginskaya, A.I.; Melik-Kasumov, T.B.; Korneeva, M.A.; Chuprina, A.V.; Zhabinskaya, A.A.; Kolyhan, S.A.; Zakharova, M.V.; Gryaznova, M.O.; Zaitsev, A.V. Beneficial effects of probiotic Bifidobacterium longum in a lithium–pilocarpine model of temporal lobe epilepsy in rats. Int. J. Mol. Sci., 2023, 24(9), 8451.
[http://dx.doi.org/10.3390/ijms24098451] [PMID: 37176158]
[99]
Hawton, K.; Hilliard, T.; Langton-Hewer, S.C.; Burren, C.; Crowne, E.C.; Hamilton-Shield, J.P.; Giri, D. Rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome – neuro-endocrine tumours (ROHHAD-NET): Case series and learning points. J. Pediatr. Endocrinol. Metab., 2023, 0(0), 418-423.
[http://dx.doi.org/10.1515/jpem-2022-0376] [PMID: 36696572]
[100]
Cryan, J.F.; O’Riordan, K.J.; Cowan, C.S.M.; Sandhu, K.V.; Bastiaanssen, T.F.S.; Boehme, M.; Codagnone, M.G.; Cussotto, S.; Fulling, C.; Golubeva, A.V.; Guzzetta, K.E.; Jaggar, M.; Long-Smith, C.M.; Lyte, J.M.; Martin, J.A.; Molinero-Perez, A.; Moloney, G.; Morelli, E.; Morillas, E.; O’Connor, R.; Cruz-Pereira, J.S.; Peterson, V.L.; Rea, K.; Ritz, N.L.; Sherwin, E.; Spichak, S.; Teichman, E.M.; van de Wouw, M.; Ventura-Silva, A.P.; Wallace-Fitzsimons, S.E.; Hyland, N.; Clarke, G.; Dinan, T.G. The microbiota-gut-brain axis. Physiol. Rev., 2019, 99(4), 1877-2013.
[http://dx.doi.org/10.1152/physrev.00018.2018] [PMID: 31460832]
[101]
Maniscalco, J.W.; Rinaman, L. Vagal interoceptive modulation of motivated behavior. Physiology, 2018, 33(2), 151-167.
[http://dx.doi.org/10.1152/physiol.00036.2017] [PMID: 29412062]
[102]
Keezer, M.R.; Sisodiya, S.M.; Sander, J.W. Comorbidities of epilepsy: Current concepts and future perspectives. Lancet Neurol., 2016, 15(1), 106-115.
[http://dx.doi.org/10.1016/S1474-4422(15)00225-2] [PMID: 26549780]
[103]
Virta, L.J.; Kolho, K.L. The risk of contracting pediatric inflammatory bowel disease in children with celiac disease, epilepsy, juvenile arthritis and type 1 diabetes-a nationwide study. J. Crohn’s Colitis, 2013, 7(1), 53-57.
[http://dx.doi.org/10.1016/j.crohns.2012.02.021] [PMID: 22445838]
[104]
Wills, A.; Hovell, C.J. Neurological complications of enteric disease. Gut, 1996, 39(4), 501-504.
[http://dx.doi.org/10.1136/gut.39.4.501] [PMID: 8944555]
[105]
Yeh, C.C.; Wang, H.H.; Chou, Y.C.; Hu, C.J.; Chou, W.H.; Chen, T.L.; Liao, C.C. High risk of gastrointestinal hemorrhage in patients with epilepsy: A nationwide cohort study. Mayo Clin. Proc., 2013, 88(10), 1091-1098.
[http://dx.doi.org/10.1016/j.mayocp.2013.06.024] [PMID: 24012412]
[106]
Camara-Lemarroy, C.R.; Escobedo-Zúñiga, N.; Ortiz-Zacarias, D.; Peña-Avendaño, J.; Villarreal-Garza, E.; Díaz-Torres, M.A. Prevalence and impact of irritable bowel syndrome in people with epilepsy. Epilepsy Behav., 2016, 63, 29-33.
[http://dx.doi.org/10.1016/j.yebeh.2016.05.041] [PMID: 27552483]
[107]
Chen, C.H.; Lin, C.L.; Kao, C.H. Irritable bowel syndrome increases the risk of epilepsy. Medicine, 2015, 94(36), e1497.
[http://dx.doi.org/10.1097/MD.0000000000001497] [PMID: 26356716]
[108]
Gil-López, F.; Boget, T.; Manzanares, I.; Donaire, A.; Conde-Blanco, E.; Baillés, E.; Pintor, L.; Setoaín, X.; Bargalló, N.; Navarro, J.; Casanova, J.; Valls, J.; Roldán, P.; Rumià, J.; Casanovas, G.; Domenech, G.; Torres, F.; Carreño, M. External trigeminal nerve stimulation for drug resistant epilepsy: A randomized controlled trial. Brain Stimul., 2020, 13(5), 1245-1253.
[http://dx.doi.org/10.1016/j.brs.2020.06.005] [PMID: 32534250]
[109]
Mercante, B.; Nuvoli, S.; Sotgiu, M.A.; Manca, A.; Todesco, S.; Melis, F.; Spanu, A.; Deriu, F. SPECT imaging of cerebral blood flow changes induced by acute trigeminal nerve stimulation in drug-resistant epilepsy. A pilot study. Clin. Neurophysiol., 2021, 132(6), 1274-1282.
[http://dx.doi.org/10.1016/j.clinph.2021.01.033] [PMID: 33867259]
[110]
Borovikova, L.V.; Ivanova, S.; Zhang, M.; Yang, H.; Botchkina, G.I.; Watkins, L.R.; Wang, H.; Abumrad, N.; Eaton, J.W.; Tracey, K.J. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature, 2000, 405(6785), 458-462.
[http://dx.doi.org/10.1038/35013070] [PMID: 10839541]
[111]
Giordano, C.; Marchiò, M.; Timofeeva, E.; Biagini, G. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets. Front. Neurol., 2014, 5, 63.
[http://dx.doi.org/10.3389/fneur.2014.00063] [PMID: 24808888]
[112]
Kshirsagar, V.Y.; Nagarsenkar, S.; Wingkar, K.C.; Ahmed, M.; Colaco, S. Abdominal epilepsy in chronic recurrent abdominal pain. J. Pediatr. Neurosci., 2012, 7(3), 163-166.
[http://dx.doi.org/10.4103/1817-1745.106468] [PMID: 23559997]
[113]
Pitra, S.; Smith, B.N. Musings on the wanderer: What’s new in our understanding of vago-vagal reflexes? VI. Central vagal circuits that control glucose metabolism. Am. J. Physiol. Gastrointest. Liver Physiol., 2021, 320(2), G175-G182.
[http://dx.doi.org/10.1152/ajpgi.00368.2020] [PMID: 33205998]
[114]
Sasselli, V.; Pachnis, V.; Burns, A.J. The enteric nervous system. Dev. Biol., 2012, 366(1), 64-73.
[http://dx.doi.org/10.1016/j.ydbio.2012.01.012] [PMID: 22290331]
[115]
Agostoni, E.; Chinnock, J.E.; Daly, M.D.B.; Murray, J.G. Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat. J. Physiol., 1957, 135(1), 182-205.
[http://dx.doi.org/10.1113/jphysiol.1957.sp005703] [PMID: 13398974]
[116]
Rush, A.J.; George, M.S.; Sackeim, H.A.; Marangell, L.B.; Husain, M.M.; Giller, C.; Nahas, Z.; Haines, S.; Simpson, R.K., Jr; Goodman, R. Vagus nerve stimulation (VNS) for treatment-resistant depressions: A multicenter study. See accompanying Editorial, in this issue. Biol. Psychiatry, 2000, 47(4), 276-286.
[http://dx.doi.org/10.1016/S0006-3223(99)00304-2] [PMID: 10686262]
[117]
Young, V.R.; Ajami, A.M. Glutamate: An amino acid of particular distinction. J. Nutr., 2000, 130(4), 892S-900S.
[http://dx.doi.org/10.1093/jn/130.4.892S] [PMID: 10736349]
[118]
Kitamura, A.; Tsurugizawa, T.; Uematsu, A.; Torii, K.; Uneyama, H. New therapeutic strategy for amino acid medicine: Effects of dietary glutamate on gut and brain function. J. Pharmacol. Sci., 2012, 118(2), 138-144.
[http://dx.doi.org/10.1254/jphs.11R06FM] [PMID: 22293294]
[119]
Tsurugizawa, T.; Uematsu, A.; Nakamura, E.; Hasumura, M.; Hirota, M.; Kondoh, T.; Uneyama, H.; Torii, K. Mechanisms of neural response to gastrointestinal nutritive stimuli: The gut-brain axis. Gastroenterology, 2009, 137(1), 262-273.
[http://dx.doi.org/10.1053/j.gastro.2009.02.057] [PMID: 19248781]
[120]
San Gabriel, A.; Uneyama, H. Amino acid sensing in the gastrointestinal tract. Amino Acids, 2013, 45(3), 451-461.
[http://dx.doi.org/10.1007/s00726-012-1371-2] [PMID: 22865248]
[121]
Sawchenko, P.E. Central connections of the sensory and motor nuclei of the vagus nerve. J. Auton. Nerv. Syst., 1983, 9(1), 13-26.
[http://dx.doi.org/10.1016/0165-1838(83)90129-7] [PMID: 6319474]
[122]
Dibué-Adjei, M.; Kamp, M.A.; Vonck, K. 30 years of vagus nerve stimulation trials in epilepsy: Do we need neuromodulation-specific trial designs? Epilepsy Res., 2019, 153, 71-75.
[http://dx.doi.org/10.1016/j.eplepsyres.2019.02.004] [PMID: 30824370]
[123]
Penry, J.K.; Dean, J.C. Prevention of intractable partial seizures by intermittent vagal stimulation in humans: {reliminary results. Epilepsia, 1990, 31(s2), S40-S43.
[http://dx.doi.org/10.1111/j.1528-1157.1990.tb05848.x] [PMID: 2121469]
[124]
FineSmith, R.B.; Zampella, E.; Devinsky, O. Vagal nerve stimulator: A new approach to medically refractory epilepsy. N. J. Med., 1999, 96(6), 37-40.
[PMID: 10384766]
[125]
Beekwilder, J.P.; Beems, T. Overview of the clinical applications of vagus nerve stimulation. J. Clin. Neurophysiol., 2010, 27(2), 130-138.
[http://dx.doi.org/10.1097/WNP.0b013e3181d64d8a] [PMID: 20505378]
[126]
van der Kooy, D.; Koda, L.Y.; McGinty, J.F.; Gerfen, C.R.; Bloom, F.E. The organization of projections from the cortes, amygdala, and hypothalamus to the nucleus of the solitary tract in rat. J. Comp. Neurol., 1984, 224(1), 1-24.
[http://dx.doi.org/10.1002/cne.902240102] [PMID: 6715573]
[127]
Krahl, S.E.; Clark, K.B.; Smith, D.C.; Browning, R.A. Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation. Epilepsia, 1998, 39(7), 709-714.
[http://dx.doi.org/10.1111/j.1528-1157.1998.tb01155.x] [PMID: 9670898]
[128]
Raedt, R.; Clinckers, R.; Mollet, L.; Vonck, K.; El Tahry, R.; Wyckhuys, T.; De Herdt, V.; Carrette, E.; Wadman, W.; Michotte, Y.; Smolders, I.; Boon, P.; Meurs, A. Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model. J. Neurochem., 2011, 117(3), 461-469.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07214.x] [PMID: 21323924]
[129]
McMillin, D.L.; Richards, D.G.; Mein, E.A.; Nelson, C.D. The abdominal brain and enteric nervous system. J. Altern. Complement. Med., 1999, 5(6), 575-586.
[http://dx.doi.org/10.1089/acm.1999.5.575] [PMID: 10630351]

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