{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:43:38Z","timestamp":1793321018122,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100124"],"award-info":[{"award-number":["82100124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Spinal cord injury (SCI) induces complex inflammatory and oxidative stress responses that exacerbate secondary damage and impair functional recovery. This study investigated the role of butyrate\u2014a microbiota\u2010derived short\u2010chain fatty acid (SCFA)\u2014in ameliorating SCI using a combination of\n                    <jats:italic>in silico<\/jats:italic>\n                    , in\u00a0vitro, and in\u00a0vivo approaches. We first performed gut microbiota 16S rRNA sequencing and targeted metabolomics to assess microbial dysbiosis and serum SCFA levels in rats post\u2010SCI. A marked reduction in butyrate\u2010producing Firmicutes and serum butyrate concentrations was observed after injury. Molecular docking predicted a direct interaction between butyrate and HDAC1, which was confirmed by a ~40% reduction in HDAC1 expression in spinal cord tissue, as demonstrated by Western blot and immunofluorescence. In microglial cultures, butyrate significantly inhibited LPS\u2009+\u2009ATP\u2010induced NLRP3 inflammasome activation by approximately 38%. For the in\u00a0vivo component, a cervical hemi\u2010contusion SCI model at the C5 level was established in rats. To restore butyrate levels, animals were either fed a high\u2010fiber diet (HFD) or received intrathecal butyrate administration. Behavioral assessment revealed a 1.5\u2010fold improvement in Forelimb Locomotor Scale scores at 1\u2009month post\u2010injury, and motor\u2010evoked potential recordings showed nearly a 1.8\u2010fold enhancement, indicating significantly improved locomotor and electrophysiological recovery in HFD\u2010treated rats compared to controls. Furthermore, HFD treatment resulted in reduced oxidative stress (as evidenced by lower MDA and DHE staining), decreased inflammation, while butyrate administration promoted M2\u2010type macrophage\/microglia polarization. These findings reveal that butyrate mitigates oxidative stress and inflammation by targeting HDAC1 and the NLRP3 inflammasome. Importantly, HFD\u2010driven restoration of microbial butyrate production represents a promising and translationally relevant non\u2010invasive therapeutic strategy to enhance SCI recovery via the gut\u2010spinal cord axis.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70250-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70250","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:25:58Z","timestamp":1760012758000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["From Molecular Docking to Rat Models: Butyrate From a High\u2010Fiber Diet Inhibits\n                    <scp>HDAC1<\/scp>\n                    and\n                    <scp>NLRP3<\/scp>\n                    Inflammasome to Alleviate Oxidative Stress and Inflammation After Spinal Cord Injury"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8886-365X","authenticated-orcid":false,"given":"Kong","family":"Ganggang","sequence":"first","affiliation":[{"name":"Department of Spinal Surgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Wenwu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital of Xinxiang Medical University  Weihui Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Spinal Surgery The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yan","sequence":"additional","affiliation":[{"name":"Medical Intensive Care Unit The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xie","family":"Baoshu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery 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