{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:55:06Z","timestamp":1791903306375,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GSA23G001"],"award-info":[{"award-number":["GSA23G001"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n CDKL5 deficiency disorder (CDD) is a developmental and epileptic encephalopathy characterized by early\u2010onset, treatment\u2010resistant seizures and severe neurodevelopmental impairment. Increasing evidence suggests that alterations in the gut\u2013brain axis may contribute to disease pathophysiology, raising interest in microbiota\u2010targeted interventions. In this study, we evaluated the effects of a prebiotic\u2010based nutritional intervention on clinical outcomes, gut microbiota composition, and fatty acid profiles in individuals with CDD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Thirteen participants with drug\u2010resistant epilepsy were enrolled (one male; median age, 12\u2009years [IQR, 8.8\u201317.5]), and ten completed the longitudinal intervention protocol. The protocol comprised two medical\u2010food interventions separated by washout periods: MF1 contained alpha\u2010lactalbumin, inulin, and fructo\u2010oligosaccharides, whereas MF2 contained the MF1 formulation supplemented with sodium butyrate. Clinical assessments, gut microbiota profiling, and fecal and systemic fatty acid measurements were performed at predefined study time points.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Seizure response varied substantially between participants. Two subjects showed a 52% and 57% reduction in monthly seizure frequency during MF1, whereas two different participants experienced reductions greater than 90% during MF2 (94% and 100%, respectively). At the cohort level, the lowest median seizure frequency was observed at the final study time point. A progressive decrease in CDD severity scale scores was also observed over the course of the study.<\/jats:p>\n \n Intervention phases coincided with transient enrichment of short\u2010chain fatty acid (SCFA)\u2010producing genera, including\n Faecalibacterium, Blautia<\/jats:italic>\n , and\n Dorea<\/jats:italic>\n . Microbiota composition differed between responders and non\u2010responders: higher seizure burden was linked to increased\n Veillonella<\/jats:italic>\n , whereas lower seizure frequency corresponded to enrichment of\n Dialister<\/jats:italic>\n and\n Gemmiger<\/jats:italic>\n . Fecal and systemic SCFA concentrations generally decreased during intervention phases, regardless of clinical response.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n Overall, these findings support a possible interaction between nutritional supplementation, microbial dynamics, and clinical manifestations in CDD. Larger studies will be necessary to clarify the therapeutic relevance of personalized microbiota\u2010targeted approaches in CDD\u2010related epilepsy.<\/jats:p>\n <\/jats:sec>\n \n Plain Language Summary<\/jats:title>\n CDKL5 deficiency disorder (CDD) is a rare condition that causes severe developmental difficulties and seizures that are difficult to control. We studied whether two medical food interventions targeting the gut microbiota, one of which also contained sodium butyrate, could influence seizures, disease severity, gut microbiota composition, and metabolite production in people with CDD. Some participants experienced substantial reductions in seizure frequency alongside changes in gut bacteria, although responses varied considerably between individuals. These preliminary findings suggest that microbiota\u2010targeted, non\u2010pharmacological approaches may have potential as supportive strategies in CDD, but larger studies are needed to confirm these observations.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/epi4.70369","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:42:01Z","timestamp":1791902521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring medical food supplementation as an adjunct strategy for microbiota restoration and seizure reduction in\n CDKL5<\/scp>\n deficiency disorder"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1893-0455","authenticated-orcid":false,"given":"Elisa","family":"Borghi","sequence":"first","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"},{"name":"Unit of Microbiology and Virology ASST Santi Paolo e Carlo Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo Domenico","family":"Marsiglia","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Triva","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerenziana","family":"Ottaviano","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"Child Neurology \u2013 Epilepsy Centre ASST Santi Paolo Carlo, Member of ERN\u2010Epicare Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Nella","family":"Savini","sequence":"additional","affiliation":[{"name":"Child Neurology \u2013 Epilepsy Centre ASST Santi Paolo Carlo, Member of ERN\u2010Epicare Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentino","family":"Costabile","sequence":"additional","affiliation":[{"name":"Unit of Microbiology and Virology ASST Santi Paolo e Carlo Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-4663","authenticated-orcid":false,"given":"Aglaia","family":"Vignoli","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 degli Studi di Milano Milan Italy"},{"name":"Childhood Neurology and Psychiatry Unit Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano (ASST GOM) Niguarda Milan 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