{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:40:19Z","timestamp":1789418419112,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Drug\u2010resistant epilepsy (DRE) is increasingly linked to neuroinflammatory mechanisms driven by gut dysbiosis. These mechanisms compromise blood\u2013brain barrier integrity, enhance seizure susceptibility, and modulate immune pathways. These insights underscore the therapeutic potential of microbiota\u2010targeted interventions in epilepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The study aimed at assessing the effectiveness of probiotics as an adjunctive therapy to enhance drug sensitivity and clinical outcomes in children with DRE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This randomized, double\u2010blind, placebo\u2010controlled trial enrolled 60 pediatric patients with DRE who were assigned to either the control group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930), which received a standard antiepileptic regimen (valproic acid, oxcarbazepine, and levetiracetam at the maximum tolerated doses) plus a daily placebo capsule, or the probiotic group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930), which received the same antiepileptic regimen plus a daily probiotic\n                      <jats:italic>\n                        (\n                        <jats:styled-content style=\"fixed-case\">Lactobacillus acidophilus<\/jats:styled-content>\n                      <\/jats:italic>\n                      ) supplement. The study duration was 6\u2009months. Assessments of clinical and biochemical outcomes were conducted at baseline and 6\u2009months after intervention. Primary end points included seizure frequency and change in quality of life as measured by the quality of life in childhood epilepsy (QOLCE\u201055) questionnaire. Secondary end points included the change in the serum levels of high\u2010mobility group box\u00a01 protein (HMGB1), interleukin\u20101\u03b2 (IL\u20101\u03b2), homocysteine (Hcy), and NLR family pyrin domain\u2010containing 3 (NLRP3).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After 6\u2009months and relative to the control group, the probiotic\n                      <jats:italic>\n                        (\n                        <jats:styled-content style=\"fixed-case\">Lactobacillus acidophilus<\/jats:styled-content>\n                      <\/jats:italic>\n                      ) group experienced a significant decline in seizure frequency (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) and a significant improvement in the QOLCE\u201055 total score (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Additionally, the probiotic group exhibited significant decreases in the serum levels of HMGB1 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0005), NLRP3 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), Hcy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), and IL\u20101\u03b2 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.05) compared with the control group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Lactobacillus acidophilus<\/jats:italic>\n                      <\/jats:styled-content>\n                      supplementation appears to enhance the effectiveness of conventional antiepileptic drugs, reduce systemic inflammation, improve quality of life, and reduce seizure frequency in children with DRE. However, further validation is necessary.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">Clinicaltrials.gov<\/jats:ext-link>\n                      Registration Number\n                    <\/jats:title>\n                    <jats:p>NCT05539287.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.70117","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:05:36Z","timestamp":1771239936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Probiotic Supplementation as an Adjuvant Therapy in Pediatric Drug\u2010Resistant Epilepsy: A Double\u2010Blind Placebo\u2010Controlled Trial"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3156-6771","authenticated-orcid":false,"given":"Amira R.","family":"Rashdan","sequence":"first","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy Tanta University  Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0882-7315","authenticated-orcid":false,"given":"Sahar M.","family":"El\u2010Haggar","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy Tanta University  Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7841-6408","authenticated-orcid":false,"given":"Ahmed Mustafa","family":"Kishk","sequence":"additional","affiliation":[{"name":"Neuro\u2010Psychiatry Department, Faculty of Medicine Tanta University  Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1071-5416","authenticated-orcid":false,"given":"Tarek M.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy Tanta University  Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"issue":"3","key":"e_1_2_11_2_1","first-page":"89","article-title":"Causes and Risk Factors of Drug\u2010Resistant Epilepsy in Children","volume":"17","author":"Nasiri J.","year":"2023","journal-title":"Iranian Journal of Child Neurology"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-016-0622-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-025-01348-w"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0022093021040013"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2024.1386205"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00063"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.03.038"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42494-021-00048-y"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21134609"},{"key":"e_1_2_11_11_1","first-page":"1","article-title":"Effects of New Antiepileptic Drugs on Homocysteine in Epileptic Patients: A Systematic Review and Meta\u2010Analysis","author":"Zheng D.","year":"2023","journal-title":"Journal of Clinical Pharmacy and Therapeutics"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-500X.130048"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2022.108637"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c332"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2020.07.012"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10296"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1276551"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2025.149597"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14142982"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70078"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2023.107190"},{"issue":"6","key":"e_1_2_11_22_1","first-page":"669","article-title":"Effects of Probiotics on Quality of Life in Children With Cystic Fibrosis; A Randomized Controlled Trial","volume":"23","author":"Jafari S. 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