{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:01:27Z","timestamp":1790755287812,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The ketogenic diet (KD) is a high\u2010fat, low\u2010carbohydrate intervention widely used to treat drug\u2010resistant epilepsy, thought to reduce seizures through a combination of metabolic, neuronal, and microbiota\u2010dependent mechanisms. Additionally, recent studies suggest that the anticonvulsant effects of KD require the gut microbiota, with taxa such as\n                      <jats:italic>Akkermansia<\/jats:italic>\n                      and\n                      <jats:italic>Parabacteroides<\/jats:italic>\n                      contributing to seizure protection by modulating host neurotransmitter balance and neural excitability. Whereas KD has been shown to be effective in reducing seizure burden across different epilepsies, its antiseizure effect on infection\u2010induced seizures, which are often driven by acute neuroinflammation, has not been determined. Here, we evaluated the effects of KD on seizure burden, neuroimmune responses, and gut microbiota composition in the Theiler's murine encephalomyelitis virus (TMEV) model of virus\u2010induced epilepsy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were maintained on either a KD or a normal diet prior to intracerebral TMEV infection. Seizures were induced by handling and scored twice daily from day 3 to 7 postinfection. Neuroimmune responses were assessed by flow cytometry, and fecal microbial composition was analyzed using 16S rRNA gene sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Despite achieving ketosis, KD did not reduce seizure incidence, seizure burden, or seizure severity during acute TMEV infection. KD also did not significantly alter overall immune cell infiltration into the central nervous system, indicating limited effects on global neuroinflammation. However, KD significantly reshaped the gut microbiota, reducing alpha diversity (richness, Shannon diversity, and evenness) and strongly altering community structure, with clear separation between diet groups, including enrichment of taxa such as\n                      <jats:italic>Akkermansia<\/jats:italic>\n                      ,\n                      <jats:italic>Acetatifactor<\/jats:italic>\n                      ,\n                      <jats:italic>Dorea,<\/jats:italic>\n                      and\n                      <jats:italic>Flintibacter<\/jats:italic>\n                      and depletion of fiber\u2010associated taxa such as\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      and\n                      <jats:italic>Roseburia<\/jats:italic>\n                      . However, these microbial shifts were not associated with protection against inflammation\u2010driven seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These results demonstrate that KD's antiseizure efficacy is highly context\u2010dependent, and that KD\u2010driven changes in microbiota\u2010 and metabolite\u2010mediated mechanisms may be ineffective against infection\u2010associated epilepsy, suggesting that inflammation\u2010driven seizures require distinct therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70509","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:41:43Z","timestamp":1790754103000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ketogenic diet fails to mitigate seizures and neuroinflammatory responses in a mouse model of virus\u2010induced epilepsy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-3440","authenticated-orcid":false,"given":"Casey H.","family":"Meili","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Doty","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Del Fiol","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Beatriz","family":"DePaula\u2010Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S0140-6736(18)32596-0","article-title":"Epilepsy in adults","volume":"393","author":"Thijs RD","year":"2019","journal-title":"Lancet (London, England)"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1111\/j.1528-1167.2008.01579.x","article-title":"The prevalence of epilepsy and pharmacoresistant epilepsy in adults: a population\u2010based study in a Western European country","volume":"49","author":"Picot 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