{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:40:20Z","timestamp":1789418420866,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tuberous sclerosis complex (TSC) presents with a broad clinical spectrum. While some individuals exhibit mild symptoms, most experience seizures and neuropsychiatric comorbidities. Emerging evidence suggests that both genetic and environmental factors, including gut microbiota, may influence epilepsy susceptibility. The microbiota\u2013gut\u2013brain axis (MGBA) is a key communication pathway through which intestinal microbes impact the central nervous system. Although the role of the MGBA in the pathogenesis of neurological diseases, particularly seizures, has been explored in both animal models and humans, data specific to TSC are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this exploratory study, we assessed whether individuals with TSC (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f15) display a distinct gut microbial signature using V3\u2013V4 16S rRNA sequencing. Their profiles were compared with two control groups: 18 children with epilepsy (EPI) and 12 age- and sex-matched healthy controls (HC). Stool short-chain fatty acid (SCFA) levels and dietary intake were also evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No significant differences were observed among the three groups in dietary intake, SCFA and branched-chain fatty acid (BCFA) levels, or alpha-diversity. Beta-diversity analysis showed a non-significant trend toward clustering of TSC and EPI samples, indicating a shared microbial profile distinct from HC. Taxonomic analysis revealed a reduction in Firmicutes\u2014particularly the\n                      <jats:italic>Ruminococcaceae<\/jats:italic>\n                      family and the genus\n                      <jats:italic>Gemmiger<\/jats:italic>\n                      \u2014in both TSC and EPI groups, consistent with epilepsy-associated dysbiosis. Notably, the TSC group showed a specific enrichment in\n                      <jats:italic>Akkermansiaceae<\/jats:italic>\n                      , a feature also reported in other neurodevelopmental disorders such as CDKL5 deficiency disorder and cerebral palsy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These preliminary findings suggest that gut microbiota alterations may contribute to neuroinflammatory processes linked to epileptogenesis and comorbidities in TSC. Further studies are needed to validate these results and explore microbiota-based therapeutic strategies aimed at improving outcomes and quality of life for individuals with TSC and their caregivers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2025.1655456","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T12:21:05Z","timestamp":1763468465000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Gut microbiota signatures in tuberous sclerosis complex and epilepsy: a pilot study"],"prefix":"10.3389","volume":"19","author":[{"given":"Emerenziana","family":"Ottaviano","sequence":"first","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 Degli Studi di Milano","place":["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","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Ceccarani","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Technologies, National Research Council","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ancona","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 Degli Studi di Milano","place":["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","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"La Briola","sequence":"additional","affiliation":[{"name":"Child Neurology and Epilepsy Centre, ASST Santi Paolo e Carlo","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Bergamoni","sequence":"additional","affiliation":[{"name":"Childhood and Adolescence Neurology and Psychiatry Unit, ASST GOM Niguarda","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Teutonico","sequence":"additional","affiliation":[{"name":"Childhood and Adolescence Neurology and Psychiatry Unit, ASST GOM Niguarda","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Pompili","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Degli Studi di Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"Child Neurology and Epilepsy Centre, ASST Santi Paolo e Carlo","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Ricci","sequence":"additional","affiliation":[{"name":"Child Neurology and Epilepsy Centre, ASST Santi Paolo e Carlo","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aglaia","family":"Vignoli","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 Degli Studi di Milano","place":["Milan, Italy"]},{"name":"Childhood and Adolescence Neurology and Psychiatry Unit, ASST GOM Niguarda","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Borghi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Universit\u00e0 Degli Studi di Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1007\/s11011-025-01550-9","article-title":"Sodium butyrate ameliorates mitochondrial oxidative stress and alterations in membrane-bound enzyme activities in pentylenetetrazole-induced kindling rat model","volume":"40","author":"Adebayo","year":"2025","journal-title":"Metab. 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