{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:04:40Z","timestamp":1787317480680,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"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":["82472236"],"award-info":[{"award-number":["82472236"]}],"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":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Post\u2010cardiac arrest brain injury (PCABI) is a leading cause of death in cardiac arrest\/cardiopulmonary resuscitation (CA\/CPR) victims and long\u2010term disability in CA\/CPR survivors. Despite previous evidence indicating that the microbiota\u2010gut\u2010brain axis is critically involved in many neurological disorders, no research has hitherto established a connection between the gut microbiota and PCABI through this axis. This study aims to explore the biological roles of microbial tryptophan metabolites in the progression of PCABI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To achieve this, we pretreated rats with a cocktail of broad\u2010spectrum antibiotics (Abx) to eradicate the gut microbiota before establishing a 7\u2010min asphyxia\u2010CA\/CPR model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Remarkably, the 24\u2010h survival rate and neurological outcomes improved in Abx\/CPR rats. Fecal 16s rDNA sequencing and PICRUSt2 analysis revealed that Abx reshaped the microbial community and elevated the proportion of microbial tryptophan metabolism in rats. Metabolomic profiling suggested that Abx shifted the phenotype of microbial tryptophan metabolism from the indole pathway to the kynurenine pathway, thereby increasing the levels of the neuroprotective metabolite kynurenine in the feces, circulation, and ultimately the brain. Furthermore, the hippocampal expression of aryl hydrocarbon receptor (AhR), an endogenous receptor of kynurenine, was upregulated in Abx\/CPR rats. In\u00a0vitro experiments further demonstrated that the neuroprotective effects of kynurenine are AhR\u2010dependent and that AhR activation could negatively regulate the NLRP3 protein expression. Supporting this, results from qRT\u2013PCR, immunohistochemistry, and immunofluorescence in the rat cerebral cortex exhibited that L\u2010kynurenine inhibited NLRP3\u2010induced pyroptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provides a direct clue to the essential participation of the microbiota\u2010gut\u2010brain axis in the progression of PCABI. It demonstrates that kynurenine might attenuate PCABI by inhibiting NLRP3\u2010induced pyroptosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70381","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T01:39:29Z","timestamp":1745631569000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gut Microbial Tryptophan Metabolism Is Involved in Post\u2010Cardiac Arrest Brain Injury via Pyroptosis Modulation"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5449-9765","authenticated-orcid":false,"given":"Chenghao","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Affiliated Hangzhou First People's Hospital, School of Medicine Westlake University  Hangzhou China"},{"name":"Department of Emergency Medicine, Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou 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