{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:42:51Z","timestamp":1793281371812,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["82401618"],"award-info":[{"award-number":["82401618"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471407"],"award-info":[{"award-number":["82471407"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171382"],"award-info":[{"award-number":["82171382"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) induces secondary neuroinflammation and gut dysbiosis. This study investigated whether oral lysozyme confers neuroprotection after TBI through gut microbiota\u2010dependent metabolic reprogramming of tryptophan metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a severe TBI mouse model, neurological function, neuroinflammation, intestinal barrier integrity, and systemic immune homeostasis were assessed following oral lysozyme administration. Fecal untargeted metabolomics, antibiotic\u2010mediated microbiota depletion, and fecal microbiota transplantation (FMT) were used to explore microbiota involvement. Cerebrospinal fluid (CSF) from 10 matched pairs of patients with severe TBI was analyzed for tryptophan pathway metabolites by liquid chromatography\u2013mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lysozyme improved neurological outcomes, attenuated neuronal apoptosis and neuroinflammation, and restored peripheral CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell homeostasis. Metabolomics revealed enrichment of fecal tryptophan metabolites (indole\u20103\u2010carboxaldehyde, indolelactic acid, kynurenic acid [KYNA]) and a shift in cerebral kynurenine metabolism toward the KYNA branch. These associations were abolished by microbiota depletion and reproduced by FMT. Favorable clinical outcomes were associated with higher CSF KYNA and an elevated KYNA\/QA ratio.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral lysozyme was associated with attenuated TBI\u2010induced neuroinflammation and brain injury, potentially through gut microbiota\u2010dependent tryptophan metabolism reprogramming. Concordance between preclinical and clinical metabolomic data supports lysozyme as a candidate microbiota\u2010targeted therapeutic strategy. The KYNA\/QA ratio warrants further validation as a prognostic indicator in larger, longitudinal cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71025","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:14:27Z","timestamp":1783696467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Lysozyme Attenuates Neuroinflammation and Brain Injury After Traumatic Brain Injury Through Gut Microbiota\u2010Dependent Reprogramming of Tryptophan Metabolism"],"prefix":"10.1002","volume":"32","author":[{"given":"Zhuoying","family":"Du","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Shanghai Medical College Fudan University  Shanghai China"},{"name":"National Center for Neurological Disorders  Shanghai China"},{"name":"Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration  Shanghai 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