{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:55:27Z","timestamp":1785243327787,"version":"3.55.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T00:00:00Z","timestamp":1710547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Brain infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL\/6J mice can induce acquired epileptogenesis. Diet alters acute seizure incidence in TMEV\u2010infected mice; yet it is unclear whether intestinal dysbiosis may also impact acute or chronic behavioral comorbidities. This study thus assessed the impact of diet formulation and sterilization on acute seizure presentation, gut microbiome composition, and epilepsy\u2010related chronic behavioral comorbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Baseline fecal samples were collected from male C57BL\/6J mice (4\u2010 to 5\u2010weeks\u2010old; Jackson Labs) upon facility arrival. Mice were randomized to either autoclaved (AC) or irradiated diet (IR) (Prolab RMH 3000) or IR (Picolab 5053). Three days later, mice underwent intracerebral TMEV or phosphate\u2010buffered saline (PBS) injection. Fecal samples were collected from a subset of mice at infection (Day 0) and Day 7 post\u2010infection. Epilepsy\u2010related working memory deficits and seizure threshold were assessed 6\u2009weeks post\u2010infection. Gut microbiome diversity was determined by 16S rRNA amplicon sequencing of fecal samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TMEV\u2010infected mice displayed acute handling\u2010induced seizures, regardless of diet: 28 of 57 IR Picolab 5053 (49.1%), 30 of 41 IR Prolab RMH 3000 (73.2%), and 47 of 77 AC Prolab RMH 3000 (61%) mice displayed seizures. The number of observed seizures differed significantly by diet: IR Picolab 5053 diet\u2010fed mice had 2.2\u2009\u00b1\u20092.8 seizures (mean\u2009\u00b1\u2009standard deviation), IR Prolab RMH 3000 diet\u2010fed mice had 3.5\u2009\u00b1\u20092.9 seizures, and AC Prolab RMH 3000 diet\u2010fed mice had 4.4\u2009\u00b1\u20093.8 seizures during the 7\u2010day monitoring period. Gut microbiome composition differed significantly in TMEV\u2010infected mice fed the AC Prolab RMH 3000 diet, with measured differences in gram\u2010positive bacteria. These mice also displayed worsened long\u2010term working memory deficits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Diet\u2010induced differences in intestinal dysbiosis in the TMEV model are associated with marked changes in acute seizure presentation, symptomatic recovery, and onset of chronic behavioral comorbidities of epilepsy. Our study reveals a novel disease\u2010modifying impact of dietary manipulation on intestinal bacterial species after TMEV\u2010induced acute seizures.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.17946","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T09:04:06Z","timestamp":1710579846000},"page":"1777-1790","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Diet composition and sterilization modifies intestinal microbiome diversity and burden of Theiler's virus infection\u2013induced acute seizures"],"prefix":"10.1111","volume":"65","author":[{"given":"Dannielle K.","family":"Zierath","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Manoukian","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8982-772X","authenticated-orcid":false,"given":"Kevin M.","family":"Knox","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-4408","authenticated-orcid":false,"given":"H. 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