{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T06:50:34Z","timestamp":1764312634676,"version":"3.46.0"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8207081487"],"award-info":[{"award-number":["8207081487"]}],"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":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Sepsis\u2010associated encephalopathy (SAE) is a major contributor to mortality in septic patients, with its mechanisms being incompletely understood and effective therapies lacking. While the gut bacterium\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                      <\/jats:styled-content>\n                      (AKK) has shown beneficial effects in systemic infections, its specific role and mechanisms in SAE remain undefined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the role of AKK in a murine model of sepsis induced by cecal ligation and puncture (CLP). Oral administration of AKK was confirmed via 16S rRNA sequencing. Mice underwent behavioral assessments to evaluate cognitive function. Hippocampal levels of pro\u2010inflammatory cytokines were measured, and transcriptomic profiling was performed to identify key mediators. Functional analyses were conducted to delineate the role of the identified protein, Decorin (DCN), in neuronal survival, apoptosis, and autophagy. Simultaneously, we intervened in the expression of mouse DCN using AAV virus and further validated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Oral AKK pretreatment was successfully enriched in the gut and significantly ameliorated CLP\u2010induced cognitive deficits. It concurrently reduced hippocampal pro\u2010inflammatory cytokine levels through a robust, DCN\u2010independent anti\u2010inflammatory pathway. Transcriptomics revealed that AKK treatment notably upregulated hippocampal DCN expression. Functional studies demonstrated that DCN contributed to AKK's neuroprotective effects by promoting autophagy and suppressing neuronal apoptosis, representing a distinct mechanism of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings reveal a dual mechanism through which AKK mitigates SAE: (1) suppression of hippocampal inflammation via a DCN\u2010independent pathway, and (2) DCN\u2010dependent modulation of neuronal apoptosis and autophagy. This study establishes AKK as a promising microbial intervention for SAE and identifies DCN as a context\u2010specific mediator of its neuroprotective effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70642","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:59:45Z","timestamp":1762282785000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decorin Is a Newly Discovered Target of\n                    <scp>\n                      <i>Akkermansia muciniphila<\/i>\n                    <\/scp>\n                    in the Treatment of Sepsis\u2010Associated Encephalopathy"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4601-7893","authenticated-orcid":false,"given":"Bingqing","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Tianjin Medical University General Hospital  Tianjin 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