Voedingsgewoontes bij honden met idiopathische epilepsie

Pauline
Vynckier

Voeding wordt steeds belangrijker in de maatschappij, voor zowel mensen als dieren. Denk maar aan de vele diëtisten die geraadpleegd worden bij het willen vermageren. De grote variatie in producten. Het deel van het loon die naar voeding toegaat en ga zo maar voort. Daarnaast zouden bepaalde diëten en/of supplementen gebruikt worden voor het management van sommige ziekten, meer bepaald idiopathische epilepsie. De werkingsmechanisme die daar achter zit is zeer complex, maar er wordt verondersteld dat de voeding een effect heeft op het darmmicrobioom, die op zijn beurt de hersenen beïnvloedt.  Deze werkingsmechanisme kan ook in omgekeerde richting gaan, waarbij de hersenen het darmmicrobioom beïnvloeden. Daarnaast is geweten dat de hersenen cruciaal zijn voor het initiëren van de idiopathische epilepsie, een type epilepsie dat geen aantoonbare oorzaak heeft.

Indien er op de dieren, meer specifiek de honden wordt gefocust, werd er in een studie van Benjamin Berk (2018) gezien dat eigenaren waarbij hun hond met idiopathische epilepsie werd gediagnosticeerd vaker de voeding van hun hond veranderen. De dierenarts werd slechts in één derde van de gevallen hiervoor gecontacteerd, ondanks dat het veranderen van de voeding bepaalde neveneffecten kan hebben zoals het beïnvloeden van de werking van de aanvalswerende geneesmiddelen. De hondeneigenaren gaven na de diagnose van idiopathische epilepsie vooral alternatieve voeding. Het begrip alternatieve voeding omvat een alternatief dieet en/of supplementen. Onder alternatieve diëten wordt alles wat buiten de traditionele commerciële diëten (nat- of droog voer) valt, zoals botten en rauw vlees (BARF), kant en klaar vers vlees (KVV), graanvrije voeding, dieetvoeding, vegetarische of veganistische voeders of andere mogelijke voedingen verstaan. Dit type voeding heeft ook geen duidelijke claim dat deze volledig of uitgebalanceerd is naar de noden van het dier. Onder supplementen wordt een eetbare aanvulling die op regelmatige of onregelmatige basis aan een bepaald dieet wordt toegevoegd ter ondersteuning van de gezondheid. Bekende voorbeelden zijn vitaminen en omega 3-vetzuren. Dit onderzoek werd met behulp van een enquête uitgevoerd in verschillende landen, onder andere Amerika, Engeland  en Canada. In mijn masterproef wou ik met behulp van een enquête nagaan of dit ook het geval was voor België en Nederland. Verder wou ik kijken of er een verschil was in de voedingsgewoontes voor honden met idiopathische epilepsie in vergelijking met gezonde honden. De vergelijking met voedingsgewoontes bij gezonde honden werd, voor zover geweten niet eerder beschreven in de literatuur.

Er werd een enquête in het Nederlands opgesteld die door hondeneigenaren met gezonde honden en honden met epilepsie op een sociale platform voor twee maand lang te raadplegen was. Na het uitvoeren van de enquête en de antwoorden te hebben onderworpen aan de selectiecriteria konden van de 1826 verkregen antwoorden 756 gezonde honden en 45 honden met idiopathische epilepsie die voldeden aan de eerste betrouwbaarheidsinterval bij het stellen van de diagnose volgens de International Veterinary Epilepsy Task Force behouden worden. Er wordt aan de eerste betrouwbaarheidsniveau voldaan indien er geen oorzaak is die de aanvallen verklaart, de eerste epileptiforme aanval plaats vond op een leeftijd van 6 maand tot en met 6 jaar en het voor het stellen van de diagnose ook minstens een klinisch onderzoek en bloedonderzoek werd uitgevoerd door een dierenarts en waarbij de aanval zelf ook gezien werd door de dierenarts. Er werd gezien dat 46,6% van de eigenaren de voeding van hun hond met idiopathische epilepsie na de diagnose van deze ziekte hebben veranderd, dit in tegenstelling van de studie van Berk et al. (2018) waar het om 67,7% ging. Verder hebben er nog 24,44% van de hondeneigenaren dit in overweging genomen zonder de voeding dan ook effectief aan te passen. Voor het veranderen van de voeding werd er gezien dat de dierenarts slechts in één derde van de gevallen werd gecontacteerd, dit in overeenstemming met de studie van Berk et al. (2018). Daarnaast werd er gezien dat er meer gebruik werd gemaakt van een alternatieve voeding bij eigenaren met een hond met IE voor (60%) en na (95,24%) de diagnose in vergelijking met de eigenaren met gezonde honden (namelijk 40,60%). De meest gebruikte alternatieve diëten waren Kant en klaar vers vlees (KKV), granenvrije voeding en dieetvoedingen (een voorgeschreven voeding door een dierenarts voor bepaalde aandoeningen). Er zijn echter geen andere studies om deze resultaten mee te vergelijken. Het gebruik van supplementen verschilde echter miniem tussen honden met idiopathische epilepsie waar de voeding na de diagnose werd veranderd  (23, 81%) en gezonde honden (25,40%). De resultaten van deze enquête dienen echter met een zekere voorzichtigheid geëxtrapoleerd te worden, gezien ze voornamelijk ingevuld werd door Nederlandstalige vrouwen  met een leeftijd van 20-65 jaar die in het bezit zijn van een Facebook account.

Tot slot valt er te besluiten dat er heel wat te doen is rond het onderwerp voeding en het darmmicrobioom. Net minder dan de helft van de eigenaren verandert de voeding van hun hond na de diagnose van idiopathische epilepsie. Alternatieve diëten worden vooral bij honden met de idiopathische epilepsie voor en na de diagnose gebruikt in vergelijking met gezonde honden. Hierbij wordt ook maar in één derde van de gevallen de dierenarts gecontacteerd. Verder werd er geen verschil gezien tussen het gebruik van supplementen bij gezonde en honden met idiopathische epilepsie. Het verkregen inzicht in de voedingsgewoontes van eigenaars draagt bij tot het optimaal inzetten van voeding in het management van idiopathische epilepsie, ondanks er nog andere studies nodig zijn.

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Bibliografie

Alessandri, G., Milani, C., Mancabelli, L., Mangifesta, M., Lugli, G.A., Viappiani, A., Duranti, S., Turroni, F., Ossiprandi, M.C., van Sinderen, D., et al., 2019. Metagenomic dissection of the canine gut microbiota: insights into taxonomic, metabolic and nutritional features. Environ Microbiol 21, 1331–1343. Algya, K.M., Cross, T.W.L., Leuck, K.N., Kastner, M.E., Baba, T., Lye, L., de Godoy, M.R.C., Swanson, K.S., 2018. Apparent total-tract macronutrient digestibility, serum chemistry, urinalysis, and fecal characteristics, metabolites and microbiota of adult dogs fed extruded, mildly cooked, and raw diets. Journal of Animal Science 96, 3670–3683. Alves, L., Hülsmeyer, V., Jaggy, A., Fischer, A., Leeb, T., Drögemüller, M., 2011. Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic border collies. Journal of Veterinary Internal Medicine 25, 484–489. Ambrosini, Y.M., Borcherding, D., Kanthasamy, A., Kim, H.J., Willette, A.A., Jergens, A., Allenspach, K., Mochel, J.P., 2019. The gut-brain axis in neurodegenerative diseases and relevance of the canine model: A review. Frontiers in Aging Neuroscience 11, 130. Anggono, V., Huganir, R.L., 2012. Regulation of AMPA receptor trafficking and synaptic plasticity. Current Opinion in Neurobiolgy 22, 461-469. Augustin, K., Khabbush, A., Williams, S., Eaton, S., Orford, M., Cross, H., Heales, S.J.R., Walker, M.C., Williams, R.S.B., 2018. Review Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders. The Lancet Neurology 17, 84-93. Bagley, R.S., Harrington, M.L., Moore, M.P., 1996. Surgical treatments for seizure. Adaptability for Dogs. Veterinary Clinics of North America : Small Animal Practice 26, 827-842. Bailey, M.T., Dowd, S.E., Galley, J.D., Hufnagle, A.R., Allen, R.G., Lyte, M., 2011. Exposure to a social stressor alters the structure of the intestinal microbiota: Implications for stressor-induced immunomodulation. Brain, Behavior, and Immunity 25, 397–407. Bangsgaard Bendtsen, K.M., Krych, L., Sørensen, D.B., Pang, W., Nielsen, D.S., Josefsen, K., Hansen, L.H., Sørensen, S.J., Hansen, A.K., 2012. Gut Microbiota Composition Is Correlated to Grid Floor Induced Stress and Behavior in the BALB/c Mouse. PLoS One 7, e46231. Barker-Haliski, M., Steve White, H., 2015. Glutamatergic mechanisms associated with seizures and epilepsy. Cold Spring Harbor Perspectives in Medicine 5, 1–15. Belkaid, Y., Hand, T.W., 2014. Role of the microbiota in immunity and inflammation. Cell 157, 121-141. Berendt, M., Farquhar, R.G., Mandigers, P.J.J., Pakozdy, A., Bhatti, S.F.M., De Risio, L., Fischer, A., Long, S., Matiasek, K., Muñana, K., et al., 2015. International veterinary epilepsy task force consensus report on epilepsy definition, classification and terminology in companion animals. BMC Veterinary Research 11, 182. Berendt, M., Gram, L., 1999. Epilepsy and Seizure Classification in 63 Dogs: A Reappraisal of Veterinary Epilepsy Terminology. Journal of Veterinary Inernal Medicine 13, 14-20. Berendt, M., Gredal, H., Alving, J., 2004. Characteristics and phenomenology of epileptic partial seizures in dogs: Similarities with human seizure semiology. Epilepsy Research 61, 167–173. 46 Berendt, M., Gredal, H., Pedersen, L.G., Alban, L., Alving, J., 2002. A Cross-Sectional Study of Epilepsy in Danish Labrador Retrievers: Prevalence and Selected Risk Factors. Journal of Veterinary Internal Medicine 16. 262-268. Berendt, M., Hogenhave, H., Flagstad, A., Dam, M., 1999. Electroencephalography in dogs with epilepsy: similarities between human and canine findings. ACTA Neurologica SCandinavica 99, 276-283. Berg, A.T., Berkovic, S.F., Brodie, M.J., Buchhalter, J., Cross, J.H., Van Emde Boas, W., Engel, J., French, J., Glauser, T.A., Mathern, G.W., et al., 2010. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 51, 676–685. Berg, A.T., Scheffer, I.E., 2011. New concepts in classification of the epilepsies: Entering the 21st century. Epilepsia 52, 1058-1062. Berk, B.A., Law, T.H., Packer, R.M.A., Wessmann, A., Bathen-Nöthen, A., Jokinen, T.S., Knebel, A., Tipold, A., Pelligand, L., Meads, et al., 2020. A multicenter randomized controlled trial of medium-chain triglyceride dietary supplementation on epilepsy in dogs. Journal of Veterinary Internal Medicine 34, 1248–1259. Berk, B.A., Packer, R.M.A., Law, T.H., Volk, H.A., 2018. Investigating owner use of dietary supplements in dogs with idiopathic epilepsy. Research in Veterinary Science 119. 2076-284. Berk, B.A., Packer, R.M.A., Law, T.H., Wessmann, A., Bathen-Nöthen, A., Jokinen, T.S., Knebel, A., Tipold, A., Pelligand, L., Volk, H.A., 2019. A double-blinded randomised dietary supplement crossover trial design to investigate the short-term influence of medium chain fatty acid (MCT) supplement on canine idiopathic epilepsy: Study protocol. BMC Veterinary Research 15, 181. Bhatti, S.F.M., De Risio, L., Muñana, K., Penderis, J., Stein, V.M., Tipold, A., Berendt, M., Farquhar, R.G., Fischer, A., Long, S., et al., 2015. International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe. BMC Veterinary Research 11, 176. Boonstra, E., de Kleijn, R., Colzato, L.S., Alkemade, A., Forstmann, B.U., Nieuwenhuis, S., 2015. Neurotransmitters as food supplements: The effects of GABA on brain and behavior. Frontiers in Psychology 6, 1520. Boothe, D.M., 1998. Anticonvulsant therapy in small animals. Veterinary Clinics of North America: Small Animal Practice 28, 411-448. Boothe, D.M., Dewey, C., Carpenter, D.M., 2012. Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs. Journal of the American Veterinary Medical Association 240, 1073–1083. Bosch, G., Beerda, B., Hendriks, W.H., Van Der Poel, A.F.B., Verstegen, M.W.A., 2007. Impact of nutrition on canine behaviour: Current status and possible mechanisms. Nutrition Research Reviews 20, 180-194. Bough, K.J., Rho, J.M., 2007. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia 48, 43-58. Brandt, C., Mula, M., 2016. Anxiety disorders in people with epilepsy. Epilepsy and Behavior 59, 87-91. Brauer, C., Jambroszyk, M., Tipold, A., 2011. Metabolic and toxic causes of canine seizure disorders: A retrospective study of 96 cases. Veterinary Journal 187, 272–275. Chandler, K., 2006. Canine epilepsy: What can we learn from human seizure disorders?. Veterinary Journal 172, 207–217. 47 Chang, Y., Mellor, D.J., Anderson, T.J., 2006. Idiopathic epilepsy in dogs: Owners’ perspectives on management with phenobarbitone and/or potassium bromide. Journal of Small Animal Practice 47, 574- 581. Charalambous, M., Brodbelt, D., Volk, H.A., 2014. Treatment in canine epilepsy - A systematic review. BMC Veterinary Research 10, 257. Charalambous, M., Shivapour, S.K., Brodbelt, D.C., Volk, H.A., 2016. Antiepileptic drugs’ tolerability and safety - a systematic review and meta-analysis of adverse effects in dogs. BMC Veterinary Research 12, 79. Clanton, R.M., Wu, G., Akabani, G., Aramayo, R., 2017. Control of seizures by ketogenic diet-induced modulation of metabolic pathways. Amino Acids 49, 1-20. Collins, S.M., Bercik, P., 2009. The Relationship Between Intestinal Microbiota and the Central Nervous System in Normal Gastrointestinal Function and Disease. Gastroenterology 136, 2003–2014. Cryan, J.F., Dinan, T.G., 2012. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience 13, 701-712. Dagorn, A., Hillion, M., Chapalain, A., Lesouhaitier, O., Duclairoir Poc, C., Vieillard, J., Chevalier, S., Taupin, L., Le Derf, F., Feeuilloley, M.G.J., 2013. Gamma-aminobutyric acid acts as a specific virulence regulator in pseudomonas aeruginosa. Microbiology (United Kingdom) 159, 339–351. Danbolt, N.C., 2001. Glutamate uptake. Progress in Neurobiology 65, 1-105. David, L.A., Maurice, C.F., Carmody, R.N., Gootenberg, D.B., Button, J.E., Wolfe, B.E., Ling, A. V., Devlin, A.S., Varma, Y., Fischbach, M.A., et al., 2014. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563. De Caro, C., Iannone, L.F., Citraro, R., Striano, P., De Sarro, G., Constanti, A., Cryan, J.F., Russo, E., 2019. Can we ‘seize’ the gut microbiota to treat epilepsy?. Neuroscience and Biobehavioral Reviews 107, 750-764. De Giorgio, C.M., Miller, P.R., Harper, R., Gornbein, J., Schrader, L., Soss, J., Meymandi, S., 2015. Fish oil (n-3 fatty acids) in drug resistant epilepsy: A randomised placebo-controlled crossover study. Journal of Neurology, Neurosurgery and Psychiatry 86, 65–70. de Jong, D., Daamen, M., Majoie, M., Lambrechts, D., 2014. Ketogeen dieet: een update. Periodiek voor professionals 12, 4. De Risio, L., Bhatti, S., Muñana, K., Penderis, J., Stein, V., Tipold, A., Berendt, M., Farqhuar, R., Fischer, A., Long, S., et al., 2015. International veterinary epilepsy task force consensus proposal: Diagnostic approach to epilepsy in dogs. BMC Veterinary Research 11, 148. Dinan, T.G., Cryan, J.F., 2017. The Microbiome-Gut-Brain Axis in Health and Disease. Gastroenterol Clinics 46, 77-89. Eckburg, P.B., Bik, E.M., Bernstein, C.N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S.R., Nelson, K.E., Relman, D.A., 2005. Diversity of the Human Intestinal Microbial Flora. Science 308, 5728. Ekenstedt, K.J., Oberbauer, A.M., 2013. Inherited epilepsy in Dogs. Topics in Companion Animal Medicine 28, 51-58. Ekenstedt, K.J., Patterson, E.E., Mickelson, J.R., 2012. Canine epilepsy genetics. Mammalian Genome 23, 28– 39. 48 Erlen, A., Potschka, H., Volk, H.A., Sauter-Louis, C., O’Neill, D.G., 2018. Seizure occurrence in dogs under primary veterinary care in the UK: prevalence and risk factors. Journal of Veterinary Internal Medicine 32, 1665–1676. Erny, D., De Angelis, A.L.H., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al., 2015. Host microbiota constantly control maturation and function of microglia in the CNS. Nature Neuroscience 18, 965–977. Faith, J.J., Mcnulty, N., Rey, F.E., Gordon, J.I., 2011. Predicting a human gut microbiota’s response to diet in gnotobiotic mice. Science 333, 101-104. Falco-Walter, J.J., Scheffer, I.E., Fisher, R.S., 2018. The new definition and classification of seizures and epilepsy. Epilepsy Research 139, 73-79. Fiest, K.M., Sauro, K.M., Wiebe, S., Patten, S.B., Kwon, C.-S., Dykeman, J., Pringsheim, T., Lorenzetti, D., Jetté, N., 2016. Prevalence and incidence of epilepsy : A systematic review and meta-analysis of international studies. Neurology 89, 296-303. Finnegan, S.L., Volk, H.A., Asher, L., Daley, M., Packer, R.M.A., 2020. Investigating the potential for seizure prediction in dogs with idiopathic epilepsy: Owner-reported prodromal changes and seizure triggers. Veterinary Record 187, 152. Fisher, R.S., Acevedo, C., Arzimanoglou, A., Bogacz, A., Cross, J.H., Elger, C.E., Engel, J., Forsgren, L., French, J.A., Glynn, M., et al., 2014. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia 55, 475–482. Fisher, R.S., van Emde Boas, W., Blume, W., Elger, C., Genton, P., Lee, P., Engel, J., 2005. Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 46, 470-472. Fredsø, N., Koch, B.C., Toft, N., Berendt, M., 2014. Risk Factors for Survival in a University Hospital Population of Dogs with Epilepsy. Journal of Veterinary Internal Medicine 28, 1782–1788. García-Belenguer, S., Grasa, L., Valero, O., Palacio, J., Luño, I., Rosado, B., 2021. Gut microbiota in canine idiopathic epilepsy: Effects of disease and treatment. Animals 11, 3121. Giordano, C., Marchiò, M., Timofeeva, E., Biagini, G., 2014. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets. Frontiers in Neurology 5, 63. Goiz-Marquez, G., Caballero, S., Solis, H., Rodriguez, C., Sumano, H., 2009. Electroencephalographic evaluation of gold wire implants inserted in acupuncture points in dogs with epileptic seizures. Research in Veterinary Science 86, 152–161. Gong, X., Cai, Q., Liu, X., An, D., Zhou, D., Luo, R., Peng, R., Hong, Z., 2021. Gut flora and metabolism are altered in epilepsy and partially restored after ketogenic diets. Microbial Pathogenesis 155, 104899. Gong, X., Liu, X., Chen, C., Lin, J., Li, A., Guo, K., An, D., Zhou, D., Hong, Z., 2020. Alteration of Gut Microbiota in Patients With Epilepsy and the Potential Index as a Biomarker. Frontiers in Microbiology 11, 517797. Gorjipour, H., Darougar, S., Mansouri, M., Karimzadeh, P., Amouzadeh, M.H., Sohrabi, M.R., 2019. Hypoallergenic diet may control refractory epilepsy in allergic children: A quasi experimental study. Scientific Reports 9, 6875. Gulløv, C.H., Toft, N., Berendt, M., 2012. A Longitudinal Study of Survival in Belgian Shepherds with Genetic Epilepsy. Journal in Veterinary Internal Medicine 26, 1115–1120. 49 Hall, R., Labruyere, J., Volk, H., Cardy, T.J., 2020. Estimation of the prevalence of idiopathic epilepsy and structural epilepsy in a general population of 900 dogs undergoing MRI for epileptic seizures. Veterinary Record 187, E89. Hallböök, T., Ji, S., Maudsley, S., Martin, B., 2012. The effects of the ketogenic diet on behavior and cognition. Epilepsy Research 100, 304–309. Hamamoto, Y., Hasegawa, D., Mizoguchi, S., Yu, Y., Wada, M., Kuwabara, T., Fujiwara-Igarashi, A., Fujita, M., 2016. Retrospective epidemiological study of canine epilepsy in Japan using the International Veterinary Epilepsy Task Force classification 2015 (2003-2013): Etiological distribution, risk factors, survival time, and lifespan. BMC Veterinary Research 12, 248. Han, F.Y., Conboy-Schmidt, L., Rybachuk, G., Volk, H.A., Zanghi, B., Pan, Y., Borges, K., 2021. Dietary medium chain triglycerides for management of epilepsy: New data from human, dog, and rodent studies. Epilepsia 62, 1790-1806. Handl, S., Dowd, S.E., Garcia-Mazcorro, J.F., Steiner, J.M., Suchodolski, J.S., 2011. Massive parallel 16S rRNA gene pyrosequencing reveals highly diverse fecal bacterial and fungal communities in healthy dogs and cats. FEMS Microbiology Ecology 76, 301–310. Hart, Y.M., Sander, J.W.A.S., Johnson, A.L., Shorvon, S.D., 1990. National General Practice Study of Epilepsy: recurrence after a first seizure. The Lancet 336, 1271-1274. Hawkins, R.A., 2009. The blood-brain barrier and glutamate. The American Journal of Clinical Nutrition 90, 867S-874S. Heijtz, R.D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M.L., Forssberg, H., Pettersson, S., 2011. Normal gut microbiota modulates brain development and behavior. The Proceedings of the National Academy of Sciences 108, 3047–3052. Henderson, C.B., Filloux, F.M., Alder, S.C., Lyon, J.L., Caplin, D.A., 2005. Efficacy of the ketogenic diet as a treatment option for epilepsy: Meta-analysis. Journal of Child Neurology 21, 193–198. Heske, L., Nødtvedt, A., Jäderlund, K.H., Berendt, M., Egenvall, A., 2014. A cohort study of epilepsy among 665,000 insured dogs: Incidence, mortality and survival after diagnosis. Veterinary Journal 202, 471– 476. He, Z., Cui, B.T., Zhang, T., Li, P., Long, C.Y., Ji, G.Z., Zhang, F.M., 2017. Fecal microbiota transplantation cured epilepsy in a case with Crohn’s disease: The first report. World Journal of Gastroenterology 23, 3379– 3568. Hoban, A.E., Stilling, R.M., Ryan, F.J., Shanahan, F., Dinan, T.G., Claesson, M.J., Clarke, G., Cryan, J.F., 2016. Regulation of prefrontal cortex myelination by the microbiota. Translational Psychiatry 6, e774. Holzer, P., 2016. Neuropeptides, Microbiota, and Behavior. International Review of Neurobiology 131, 67– 89. Honneffer, J.B., Steiner, J.M., Lidbury, J.A., Suchodolski, J.S., 2017. Variation of the microbiota and metabolome along the canine gastrointestinal tract. Metabolomics 13, 26. Hülsmeyer, V., Zimmermann, R., Brauer, C., Sauter-Louis, C., Fischer, A., 2010. Epilepsy in Border Collies: Clinical manifestation, outcome, and mode of inheritance. Journal of Veterinary Internal Medicine 24, 171–178. 50 Iannone, L.F., Preda, A., Blottière, H.M., Clarke, G., Albani, D., Belcastro, V., Carotenuto, M., Cattaneo, A., Citraro, R., Ferraris, C., et al., 2019. Microbiota-gut brain axis involvement in neuropsychiatric disorders. Expert Review of Neurotherapeutics 19, 1037-1050. Iizumi, T., Battaglia, T., Ruiz, V., Perez Perez, G.I., 2017. Gut Microbiome and Antibiotics. Archives of Medical Research 48, 727-734. Jandhyala, S.M., Talukdar, R., Subramanyam, C., Vuyyuru, H., Sasikala, M., Reddy, D.N., 2015. Role of the normal gut microbiota. World Journal of Gastroenterology 21, 8836–8847. Jokinen, T.S., Metsä Honkala, L., Bergamasco, L., Viitmaa, R., Syrjä, P., Lohi, H., Snellman, M., Jeserevics, J., Cizinauskas, S., 2007. Benign Familial Juvenile Epilepsy in Lagotto Romagnolo Dogs. Journal of Veterinary Internal Medicine 21, 464-471. Jokinen, T.S., Tiira, K., Metsähonkala, L., Seppälä, E.H., Hielm-Björkman, A., Lohi, H., Laitinen-Vapaavuori, O., 2015. Behavioral abnormalities in Lagotto Romagnolo dogs with a history of benign familial juvenile epilepsy: A long-term follow-up study. Journal of Veterinary Internal Medicine 29, 1081–1087. Kearsley-Fleet, L., O’Neill, D.G., Volk, H.A., Church, D.B., Brodbelt, D.C., 2013. Prevalence and risk factors for canine epilepsy of unknown origin in the UK. Veterinary Record 172, 338. Kossoff, E., Wang, H.S., 2013. Dietary therapies for epilepsy. Biomedical Journal 36, 2–8. Kossoff, E.H., Zupec-Kania, B.A., Amark, P.E., Ballaban-Gil, K.R., Christina Bergqvist, A.G., Blackford, R., Buchhalter, J.R., Caraballo, R.H., Cross, J.H., Dahlin, M.G., et al., 2009. Optimal clinical management of children receiving the ketogenic diet: Recommendations of the International Ketogenic Diet Study Group. Epilepsia 50, 304-317. Kossoff, E.H., Zupec-Kania, B.A., Auvin, S., Ballaban-Gil, K.R., Christina Bergqvist, A.G., Blackford, R., Buchhalter, J.R., Caraballo, R.H., Cross, J.H., 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, 175–192. Kverneland, M., Taubøll, E., Selmer, K.K., Iversen, P.O., Nakken, K.O., 2015. Modified Atkins diet may reduce serum concentrations of antiepileptic drugs. Acta Neurologica Scandinavica 131, 187–190. Kwan, P., Arzimanoglou, A., Berg, A.T., Brodie, M.J., Hauser, W.A., Mathern, G., Moshé, S.L., Perucca, E., Wiebe, S., French, J., 2010. Defenition of drug resitant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsie 5, 1069-1077. Kwan, P., Brodie, M.J.. 2005. Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia 46, 224-235. Kwon, O.Y., Park, S.P., 2014. Depression and anxiety in people with epilepsy. Journal of Clinical Neurology 10, 175-188. Lane, S.B., Bunch, S.E., 1990. Medical Management of Recurrent Seizures in Dogs and Cats. Journal of Veterinary Internal Medicine 4, 26-39. Law, T.H., Davies, E.S.S., Pan, Y., Zanghi, B., Want, E., Volk, H.A., 2015. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy. British Journal of Nutrition 114, 1438–1447. Law, T.H., Volk, H.A., Pan, Y., Zanghi, B., Want, E.J., 2018. Metabolic perturbations associated with the consumption of a ketogenic medium-chain TAG diet in dogs with idiopathic epilepsy. British Journal of Nutrition 120, 484–490. 51 Lazarowski, A., Czornyj, L., Lubienieki, F., Girardi, E., Vazquez, S., D’Giano, C., 2007. ABC transporters during epilepsy and mechanisms underlying multidrug resistance in refractory epilepsy. Epilepsia 48, 140–149. Lee, K., Kim, N., Shim, J.O., Kim, G.H., 2021. Gut bacterial dysbiosis in children with intractable epilepsy. Journal of Clinical Medicine 10, 1–12. Leite, J.P., Neder, L., Arisi, G.M., Carlotti J.C.J., Assirati, J.A., Moreira, J.E., 2005. Plasticity, Synaptic Strength, and Epilepsy: What Can We Learn from Ultrastructural Data?. Epilepsia 46, 134-141. Li H.F., Zou Y., Ding G., 2013. Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a Meta-analysis. Iranian Journal of Pediatrics 23, 613-620. Li, M., Wang, B., Zhang, M., Rantalainen, M., Wang, S., Zhou, H., Zhang, Y., Shen, J., Pang, X., et al., 2008. Symbiotic gut microbes modulate human metabolic phenotypes. The Proceedings of the National Academy of Sciences 105, 2117-2122. Librizzi, L., Noè, F., Vezzani, A., De Curtis, M., Ravizza, T., 2012. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood-brain barrier damage. Annals of Neurology 72, 82–90. Lindefeldt, M., Eng, A., Darban, H., Bjerkner, A., Zetterström, C.K., Allander, T., Andersson, B., Borenstein, E., Dahlin, M., Prast-Nielsen, S., 2019. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. NPJ Biofilms Microbiomes 5, 5. Liu, x., Han, Q., 2015. Comparison of Health-Related Quality of Life Impairment in Children With Different Seizure Types. Clinical pediatrics 54, 1334-1338. Löscher, W., 1997. Animal models of intractable epilepsy. Progress in Neurobiology 53, 239-258. Löscher, W., Potschka, H., Rieck, S., Tipold, A., Rundfeldt, C., 2004. Anticonvulsant Efficacy of the Low-affinity Partial Benzodiazepine Receptor Agonist ELB 138 in a Dog Seizure Model and in Epileptic Dogs with Spontaneously Recurrent Seizures. Epilepsia 45, 1228-1239. Löscher W., Schwartz-Porsche D., Frey H.H., Schmidt D., 1985. Evaluation of epileptic dogs as an animal model of human epilepsy. Arzneimittel-forschun 3, 82-87. March, P.A., 1998. Seizures: Classification, Etiologies, and Pathophysiology. Clinical Techniques in SmallAmmal Practice 13, 119-131. Marguire, P.J., Dacvim, D., Fettman, M.J., Smith, M.O., Greco, D.S., Turner, A.S., Walton, J.A., Ogilvie, G.K., 2000. Effects of diet on pharmacokinetics of phenobarbital in healthy dogs. Journal of the American Veterinary Medical Association 217, 847-852. Maguire, P.J., Salpekar, J.A., 2013. Stress, seizures, and hypothalamic-pituitary-adrenal axis targets for the treatment of epilepsy. Epilepsy and Behavior 26, 352-362. Marlé, V., Bhatti, S., Van Ham, L., 2011. Primaire idiopathische epilepsie bij de hond: praktische aanpak en een update van de behandeling. Vlaams Diergeneeskundig Tijdschrift 80, 296–304. Martin-McGill, K.J., Bresnahan, R., Levy, R.G., Cooper, P.N., 2020. Ketogenic diets for drug-resistant epilepsy. Cochrane Database of Systematic Reviews 6, CD001903. Mayer, E.A., 2011. Gut feelings: The emerging biology of gut-"brain communication. Nature Reviews Neuroscience 12n 453-466. Mazzoli, R., Pessione, E., 2016. The neuro-endocrinological role of microbial glutamate and GABA signaling. Frontiers in Microbiology 7, 1934. 52 Mehrpouya-Bahrami, P., Chitrala, K.N., Ganewatta, M.S., Tang, C., Murphy, E.A., Enos, R.T., Velazquez, K.T., McCellan, J., Nagarkatti, M., Nagarkatti, P., 2017. Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity. Scientific Reports 7, 15645. Mengoni, F., Salari, V., Kosenkova, I., Tsenov, G., Donadelli, M., Malerba, G., Bertini, G., Del Gallo, F., Fabene, P.F., 2021. Gut microbiota modulates seizure susceptibility. Epilepsia 62, e153–e157. Middelbos, I.S., Boler, B.M.V., Qu, A., White, B.A., Swanson, K.S., Fahey, G.C., 2010. Phylogenetic Characterization of Fecal Microbial Communities of Dogs Fed Diets with or without Supplemental Dietary Fiber Using 454 Pyrosequencing. PLoS One 5, e9768. Molina, J., Jean-Philippe, C., Conboy, L., Añor, S., De La Fuente, C., Wrzosek, M.A., Spycher, A., Luchsinger, E., Wenger-Riggenbach, B., Montoliu, P., et al., 2020. Efficacy of medium chain triglyceride oil dietary supplementation in reducing seizure frequency in dogs with idiopathic epilepsy without cluster seizures: A non-blinded, prospective clinical trial. Veterinary Record 187, 356. Monteiro, R., Adams, V., Keys, D., Platt, S.R., 2012. Canine idiopathic epilepsy: Prevalence, risk factors and outcome associated with cluster seizures and status epilepticus. Journal of Small Animal Practice 53, 526–530. Mori, A., Goto, A., Kibe, R., Oda, H., Kataoka, Y., Sako, T., 2019. Comparison of the effects of four commercially available prescription diet regimens on the fecal microbiome in healthy dogs. Journal of Veterinary Medical Science 12, 1783-1790. Muccioli, G.G., Naslain, D., Bäckhed, F., Reigstad, C.S., Lambert, D.M., Delzenne, N.M., Cani, P.D., 2010. The endocannabinoid system links gut microbiota to adipogenesis. Molecular Systems Biology 6, 392. Muegge, B.D., Kuczynski, J., Knights, D., Clemente, J.C., Gonzalez, A., Fonatana, L., Henrissat, B., Knight, R., Gordon, J.I. 2011. Diet drives convergence in gut microbiome funtions across mammalian phylogeny and within humans. Science 332, 970-974. Mula, M., 2013. Treatment of anxiety disorders in epilepsy: An evidence-based approach. Epilepsia 54, 13– 18. Muñana, K.R., 2013a. Management of refractory epilepsy. Top in Companion Animal Medicine 28, 67-71. Muñana, K.R., 2013b. Update: Seizure Management in Small Animal Practice. Veterinary Clincs: Small Animal Practice 43, 1127-1147 Muñana, K.R., Nettifee-Osborne, J.A., Bergman, R.L., Mealey, K.L., 2012. Association between ABCB1 Genotype and Seizure Outcome in Collies with Epilepsy. The Journal of Veterinary Internal Medicine 26, 1358–1364. Muñana, K.R., Vitek, S.M., Traver, W.B., Saito, M., Skeen, T.M., Sharp, N.J.H., Olby, N.J., Haglund, M.M., 2002. Use of vagal nerve stimilation as a treatment for refractory epilepsy in dogs. Journal of the American Veterinary Medical Association. 221, 977–983. Nathan, J., Bailur, S., Datay, K., Sharma, S., Khedekar Kale, D., 2019. A Switch to Polyunsaturated Fatty Acid Based Ketogenic Diet Improves Seizure Control in Patients with Drug-resistant Epilepsy on the Mixed Fat Ketogenic Diet: A Retrospective Open Label Trial. Cureus 11, e6399. Neal, E.G., Chaff, H., Schwartz, R.H., Lawson, M.S., Edwards, N., Fitzsimmons, G., Whitney, A., Cross, H., 2008. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. The Lancet Neurology 7, 500-506. 53 Nettifee, J.A., Muñana, K.R., Griffith, E.H., 2017. Evaluation of the impacts of epilepsy in dogs on their caregivers. The Journal of the American Animal Hospital Association 53, 143–149. Newell, C., Bomhof, M.R., Reimer, R.A., Hittel, D.S., Rho, J.M., Shearer, J., 2016. Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder. Molecular Autism 7, 37. Obermeier, B., Daneman, R., Ransohoff, R.M., 2013. Development, maintenance and disruption of the bloodbrain barrier. Nature Medicine 19, 1584-1594. Olson, C.A., Vuong, H.E., Yano, J.M., Liang, Q.Y., Nusbaum, D.J., Hsiao, E.Y., 2018. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell 173, 1728-1741. O’Mahony, S.M., Marchesi, J.R., Scully, P., Codling, C., Ceolho, A.M., Quigley, E.M.M., Cryan, J.F., Dinan, T.G., 2009. Early Life Stress Alters Behavior, Immunity, and Microbiota in Rats: Implications for Irritable Bowel Syndrome and Psychiatric Illnesses. Biological Psychiatry 65, 263–267. Packer, R.M.A., Law, T.H., Davies, E., Zanghi, B., Pan, Y., Volk, H.A., 2016. Effects of a ketogenic diet on ADHDlike behavior in dogs with idiopathic epilepsy. Epilepsy and Behavior 55, 62–68. Packer, R.M.A., McGreevy, P.D., Pergande, A., Volk, H.A., 2018a. Negative effects of epilepsy and antiepileptic drugs on the trainability of dogs with naturally occurring idiopathic epilepsy. Applied Animal Behaviour Science 200, 106–113. Packer, R.M.A., McGreevy, P.D., Salvin, H.E., Valenzuela, M.J., Chaplin, C.M., Volk, H.A., 2018b. Cognitive dysfunction in naturally occurring canine idiopathic epilepsy. PLoS One 13, e0192182. Packer, R.M.A., Shihab, N.K., Torres, B.B.J., Volk, H.A., 2014. Clinical risk factors associated with anti-epileptic drug responsiveness in canine epilepsy. PLoS One 9, e106026 Packer, R.M.A., Volk, H.A., 2015. Epilepsy beyond seizures: A review of the impact of epilepsy and its comorbidities on health-related quality of life in dogs. Veterinary Record 177, 306-315. Pekcec, A., Unkrüer, B., Stein, V., Bankstahl, J.P., Soerensen, J., Tipold, A., Baumgärtner, W., Potschka, H., 2009. Over-expression of P-glycoprotein in the canine brain following spontaneous status epilepticus. Epilepsy Research 83, 144–151. Peng, A., Qiu, X., Lai, W., Li, W., Zhang, L., Zhu, X., He, S., Duan, J., Chen, L., 2018. Altered composition of the gut microbiome in patients with drug-resistant epilepsy. Epilepsy Research 147, 102–107. Pertwee, R.G., 2006. The pharmacology of cannabinoid receptors and their ligands: an overview. International Journal of Obesity 30, S13-S18. Pilla, R., Gaschen, F.P., Barr, J.W., Olson, E., Honneffer, J., Guard, B.C., Blake, A.B., Villanueva, D., Khattab, M.R., AlShawaqfeh, M., et al., 2020a. Effects of metronidazole on the fecal microbiome and metabolome in healthy dogs. The Journal of Veterinary Internal Medicine 34, 1853–1866. Pilla, R., Law, T.H., Pan, Y., Zanghi, B.M., Li, Q., Want, E.J., Lidbury, J.A., Steiner, J.M., Suchodolski, J.S., Volk, H.A., 2020b. The Effects of a Ketogenic Medium-Chain Triglyceride Diet on the Feces in Dogs With Idiopathic Epilepsy. Frontiers in Veterinary Science 7, 541547. Pitkänen, A., Lukasiuk, K., Dudek, F.E., Staley, K.J., 2015. Epileptogenesis. Cold Spring Harbor Perspectives in Medicine 5, a022822. Platt, S.R., McDonnell, J.J., 2000. Status epilepticus : Clinical features and pathofysiology. Compendium on Continuing Education for the Practicing Veterinarian. 22, 660. 54 Podell, M., 2013. Antiepileptic drug therapy and monitoring. Topics in Companion Animal Medicine 28, 59- 66. Podell, M., 1998. Antiepileptic Drug Therapy. Clincal Techniques in Small Animal Practice 13, 185-192. Podell, M., Fenner, W.R., 1993. Bromide Therapy in Refractory Canine Idiopathic Epilepsy. Journal of Veterinary Internal Medicine 7, 318-327. Potschka, H., Bhatti, S.F.M., Tipold, A., McGrath, S., 2022. Cannabidiol in canine epilepsy. Veterinary Journal 290, 105913. Potschka, H., Fischer, A., Löscher, W., Patterson, N., Bhatti, S., Berendt, M., De Risio, L., Farquhar, R., Long, S., Mandigers, P., et al., 2015. International veterinary epilepsy task force consensus proposal: Outcome of therapeutic interventions in canine and feline epilepsy. BMC Veterinary Research 11, 177. Potschka, H., Fischer, A., Von Rüden, E.L., Hülsmeyer, V., Baumgärtner, W., 2013. Canine epilepsy as a translational model?. Epilepsia 54, 571-579. Puchowicz, M.A., Smith, C.L., Bomont, C., Koshy, J., David, F., Brunengraber, H., 2000. Dog model of therapeutic ketosis induced by oral administration of R,S-1,3-butanediol diacetoacetate. The Journal of Nutritional Biochemistry 11, 281-287. Reddy, K.E., Kim, H.R., Jeong, J.Y., So, K.M., Seul, L., Ji, S.Y., Minji, K., Lee, H.J., Sungdae, L., Kim, K.H., et al., 2019. Impact of breed on the fecal microbiome of dogs under the same dietary condition. Journal of Microbiology and Biotechnology 29, 1947–1956. Remy, S., Beck, H., 2006. Molecular and cellular mechanisms of pharmacoresistance in epilepsy. Brain 129, 18-35. Riazi, K., Galic, M.A., Kuzmiski, J.B., Ho, W., Sharkey, K.A., Pittman, Q.J., 2008. Microglial activation and TNF production mediate altered CNS excitability following peripheral inflammation. The proceedings of the National Academy of Sciences 105, 17151-17156. Riazi, K., Honar, H., Homayoun, H., Demehri, S., Bahadori, M., Dehpour, A.R., 2004. Intestinal inflammation alters the susceptibility to pentylenetetrazole-induced seizure in mice. Journal of Gastroenterology and Hepatology 19, 270-277. Robinson, K., Platt, S., Stewart, G., Reno, L., Barber, R., Boozer, L., 2020. Feasibility of Non-Invasive Vagus Nerve Stimulation (gammaCore VETTM) for the Treatment of Refractory Seizure Activity in Dogs. Frontiers in Veterinary Science 7, 569739. Rogawski, M.A., Johnson, M.R., 2008. Intrinsic severity as a determinant of antiepileptic drug refractoriness. Epilepsy Currents 8, 127-130. Rogawski, M.A., Löscher, W., Rho, J.M., 2016. Mechanisms of action of Antiseizure Drugs and the Ketogenic diet. Cold Spring Harbor Perspectives in Medicine 6, 28. Rothschild, D., Weissbrod, O., Barkan, E., Kurilshikov, A., Korem, T., Zeevi, D., Costea, P.I., Godneva, A., Kalka, I.N., Bar, N., et al., 2018. Environment dominates over host genetics in shaping human gut microbiota. Nature 555, 210–215. Round, J.L., Mazmanian, S.K., 2009. The gut microbiota shapes intestinal immune responses during health and disease. Nature Reviews Immunology 9, 313-323. 55 Royaux, E., Van Ham, L., Broeckx, B.J.G., Van Soens, I., Gielen, I., Deforce, D., Bhatti, S.F.M., 2017. Phenobarbital or potassium bromide as an add-on antiepileptic drug for the management of canine idiopathic epilepsy refractory to imepitoin. Veterinary Journal 220, 51–54. Roynard, P., Frank, L., Xie, H., Fowler, M., 2018. Acupuncture for Small Animal Neurologic Disorders. Veterinary Clinics: Small Animal Practice 48, 201-219 Safak, B., Altunan, B., Topçu, B., Topkaya, A.E., 2020. The gut microbiome in epilepsy. Microbial Pathogenesis 139, 103853. Sandhu, K. V., Sherwin, E., Schellekens, H., Stanton, C., Dinan, T.G., Cryan, J.F., 2017. Feeding the microbiotagut-brain axis: diet, microbiome, and neuropsychiatry. Translational Research 179, 223-244. Scarsella, E., Stefanon, B., Cintio, M., Licastro, D., Sgorlon, S., Dal Monego, S., Sandri, M., 2020. Learning machine approach reveals microbial signatures of diet and sex in dog. PLoS One 15, e0237874. Scheperjans, F., Aho, V., Pereira, P.A.B., Koskinen, K., Paulin, L., Pekkonen, E., Haapaniemi, E., Kaakkola, S., Eerola-Rautio, J., Pohja, M., et al., 2015. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Movement Disorders 30, 350–358. Schinkel, A.H., Smit, J.J.M., Van Tellingen, 0., Beijnen, J.H., Wagenaar, E., Van Deemter, L., Mel, C.A.A.M., Van Der Valk, M.A., Robanus-Maandag, E.C., Te Riele, H.P.J., et al., 1994. Disruption of the Mouse m&la PGlycoprotein Gene Leads to a Deficiency in the Blood-Brain Barrier and to Increased Sensitivity to Drugs. Cell 77, 491-502. Schinkel, A.H., Wagenaar, E., Mol, C.A.A.M., Van Deemter, L., 1996. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. Journal of Clinical Investigation 97, 2517–2524. Schrickx, J.A., Fink-Gremmels, J., 2008. Implications of ABC transporters on the disposition of typical veterinary medicinal products. European Journal of Pharmacology 585, 510-519. Scorza, F.A., Cavalheiro, E.A., Arida, R.M., Terra, V.C., Scorza, C.A., Ribeiro, M.O., Cysneiros, R.M., 2009. Positive impact of omega-3 fatty acid supplementation in a dog with drug-resistant epilepsy: A case study. Epilepsy and Behavior 15, 527–528. Seppälä, E.H., Koskinen, L.L.E., Gulløv, C.H., Jokinen, P., Karlskov-Mortensen, P., Bergamasco, L., Baranowska Körberg, I., Cizinauskas, S., Oberbauer, A.M., Berendt, M., et al., 2012. Identification of a novel idiopathic epilepsy locus in Belgian Shepherd dogs. PLoS One 7, e33549. Shaw N, Trepanier LA, Center SA, Garland S. 1996. High dietary chloride content associated with loss of therapeutic serum bromide concentrations in an epileptic dog. Journal of the American Veterinary Medical Association. 208(2):234-236. Sherwin, E., Dinan, T.G., Cryan, J.F., 2018. Recent developments in understanding the role of the gut microbiota in brain health and disease. The New York Academy of Sciences 1420, 5-25. Shihab, N., Bowen, J., Volk, H.A., 2011. Behavioral changes in dogs associated with the development of idiopathic epilepsy. Epilepsy and Behavior 21, 160–167. Shorvon, S.D., 2011. The etiologic classification of epilepsy. Epilepsia 52, 1052-1057. Simeone, T.A., Donevan, S.D., Rho, J.M., 2003. Molecular biology and ontogeny of y-Aminobutyric Acid (GABA) receptors in the mammalian central nervous system. Journal of Child Neurology 18, 39–49. Skerritt, G., 1988. Canine epilepsy. In Practice 45, 27-30. 56 Stephen, L.J., Brodie, M.J., 2009. Selection of Antiepileptic Drugs in Adults. Neurologic Clinics 27, 967-992. Suchodolski, J.S., 2021. Analysis of the gut microbiome in dogs and cats. Veterinary Clinical Pathology 50, 6- 17. Suchodolski, J.S., 2011. Intestinal microbiota of dogs and cats: A bigger world than we thought. Veterinary Clinics: Small Animal Practice 41, 261-272. Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X.N., Kubo, C., Koga, Y., 2004. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. Journal of Physiology 558, 263–275. Swanson, K.S., Dowd, S.E., Suchodolski, J.S., Middelbos, I.S., Vester, B.M., Barry, K.A., Nelson, K.E., Torralba, M., Henrissat, B., Coutinho, P.M., Cann, I.K., et al., 2011. Phylogenetic and gene-centric metagenomics of the canine intestinal microbiome reveals similarities with humans and mice. ISME Journal 5, 639– 649. Tagliabue, A., Ferraris, C., Uggeri, F., Trentani, C., Bertoli, S., de Giorgis, V., Veggiotti, P., Elli, M., 2017. Shortterm impact of a classical ketogenic diet on gut microbiota in GLUT1 Deficiency Syndrome: A 3-month prospective observational study. Clinical Nutrition ESPEN 17, 33–37. Takanaga, H., Ohtsuki, S., Hosoya, K., Terasaki, T., 2001. GAT2/BGT-1 as a System Responsible for the Transport of-Aminobutyric Acid at the Mouse Blood-Brain Barrier. Journal of Cerebral Blood Flow and Metabolism 21, 1232-1239. Terrone, G., Pauletti, A., Pascente, R., Vezzani, A., 2016. Preventing epileptogenesis: A realistic goal?. Pharmacological Research 110, 96–100. The WHOQOL group, 1995. The world health organization quality of life assessment (whoqol): position paper from the world health organization. Social Science and Medicine 41, 1403-1409. Thiebaut, F., Tsuruot, T., Hamadat, H., Gottesman, M.M., Pastan, I., Willingham, M.C., 1987. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues . The Proceedings of the National Academy of Sciences 84, 7735-7738. Thomas, W.B., 2010. Idiopathic Epilepsy in Dogs and Cats. Veterinary Clinics: Small Animal Practice 40, 161- 179. Thomas, W.B., 2000. Idiopathic epilepsy in dogs. Veterinary Clinics of North America: Small Animal Practica 30, 183-206. Thurman, G.D., Mcfadyen, M.L., Miller, R., 1990. The pharmacokinetics of phenobarbitone in fasting and nonfasting dogs. Journal of the South African Veterinary Association 61, 86-89. Tipold, A., Keefe, T.J., Löscher, W., Rundfeldt, C., de Vries, F., 2015. Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs. Journal of Veterinary Pharmacology and Therapeutics 38, 160–168. Turnbaugh, P.J., Ridaura, V.K., Faith, J.J., Rey, F.E., Knight, R., Gordon, J.I., 2009. The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice. Science Translational Medicine 1, 6ra14. Turrigiano, G., 2012. Homeostatic synaptic plasticity: Local and global mechanisms for stabilizing neuronal function. Cold Spring Harbor Perspectives in Biology 4, a005736. 57 Uneyama, H., Niijima, A., San Gabriel, A., Torii, K., 2006. Luminal amino acid sensing in the rat gastric mucosa. American Journal of Physiology 291, 1163–1170. Urkasemsin, G., Olby, N.J., 2014. Canine paroxysmal movement disorders. Veterinary Clinics: Small Animal Practice 44, 1091-1102. van Vliet, E.A., van Schaik, R., Edelbroek, P.M., Redeker, S., Aronica, E., Wadman, W.J., Marchi, N., Vezzani, A., Gorter, J.A., 2006. Inhibition of the Multidrug Transporter P-Glycoprotein Improves Seizure Control in Phenytoin-treated Chronic Epileptic Rats. Epilepsia 47, 672-680. Verdoodt, F., Watanangura, A., Bhatti, S.F.M., Schmidt, T., Suchodolski, J.S., Van Ham, L., Meller, S., Volk, H.A., Hesta, M., 2022. The role of nutrition in canine idiopathic epilepsy management: Fact or fiction?. The Veterinary Journal 290, 105917. Watanangura, A., Meller, S., Suchodolski, J.S., Pilla, R., Khattab, M.R., Loderstedt, S., Becker, L.F., BathenNöthen, A., Mazzuoli-Weber, G., Volk, H.A., 2022. The effect of phenobarbital treatment on behavioral comorbidities and on the composition and function of the fecal microbiome in dogs with idiopathic epilepsy. Frontiers in Veterinary Science 9, 933905. Weissl, J., Hülsmeyer, V., Brauer, C., Tipold, A., Koskinen, L.L., Kyöstilä, K., Lohi, H., Sauter-Louis, C., Wolf, M., Fischer, A., 2012. Disease progression and treatment response of idiopathic epilepsy in Australian shepherd dogs. Journal of Veterinary Internal Medicine 26, 116–125. Werner, F.M., Coveñas, R., 2017. Classical neurotransmitters and neuropeptides involved in generalized epilepsy in a multi-neurotransmitter system: How to improve the antiepileptic effect?. Epilepsy and Behavior 71, 124–129. Wernimont, S.M., Radosevich, J., Jackson, M.I., Ephraim, E., Badri, D. V., MacLeay, J.M., Jewell, D.E., Suchodolski, J.S., 2020. The Effects of Nutrition on the Gastrointestinal Microbiome of Cats and Dogs: Impact on Health and Disease. Frontiers in Microbiology 11, 1266. Wessmann, A., Volk, H.A., Packer, R.M.A., Ortega, M., Anderson, T.J., 2016. Quality-of-life aspects in idiopathic epilepsy in dogs. Veterinary Record 179, 229. Wessmann, A., Volk, H.A., Parkin, T., Ortega, M., Anderson, T.J., 2014. Evaluation of quality of life in dogs with idiopathic epilepsy. Journal of Veterinary Internal Medicine 28, 510–514. WHO., 1946. Constitution of the world health organization. American Journal of Public Health and the Nation’s Health 36, 1315-1323. Wirrell, E.C., Nabbout, R., Scheffer, I.E., Alsaadi, T., Bogacz, A., French, J.A., Hirsch, E., Jain, S., Kaneko, S., Riney, K., et al., 2022. Methodology for classification and definition of epilepsy syndromes with list of syndromes: Report of the ILAE Task Force on Nosology and Definitions. Epilepsia 63, 1333-1348. Wu, H.J., Wu, E., 2012. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes 3, 4-14. Wu, J., Zhang, Y., Yang, H., Rao, Y., Miao, J., Lu, X., 2016. Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy. Canadian Journal of Infectious Diseases and Medical Microbiology 2016, 9032809. 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., 2017. Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy. World Journal of Gastroenterology 23, 6164–6171. 58 Yatsunenko, T., Rey, F.E., Manary, M.J., Trehan, I., Dominguez-Bello, M.G., Contreras, M., Magris, M., Hidalgo, G., Baldassano, R.N., Anokhin, A.P., Heath, A.C., et al., 2012. Human gut microbiome viewed across age and geography. Nature 486. 222-227. You, I.W., Kim, M.J., 2021. Comparison of gut microbiota of 96 healthy dogs by individual traits: Breed, age, and body condition score. Animals 11, 2432. Yudkoff, M., Daikhin, Y., Nissim, Ilana, Lazarow, A., Nissim, Itzhak, 2001. Ketogenic Diet, Amino Acid Metabolism, and Seizure Control. Journal of Neuroscience Research 66, 931-940. Zhan, X., Stamova, B., Jin, L.-W., DeCarli, C., Phinney, B., Sharp, F.R., 2016. Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology 87, 2324-2332. Zhang, Y., Zhou, S., Zhou, Y., Yu, L., Zhang, L., Wang, Y., 2018. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Research 145, 163–168.

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Universiteit of Hogeschool
Universiteit Gent
Thesis jaar
2023
Promotor(en)
Fien Verdoodt, Myriam Hesta
Thema('s)
Kernwoorden