{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:15:20Z","timestamp":1793171720131,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Construction Fund of Medical Key Disciplines of Hangzhou","award":["OO20200485"],"award-info":[{"award-number":["OO20200485"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Traumatic brain injury (TBI) is a common cause of disability and mortality, affecting millions of people every year. The neuroinflammation and immune response post-TBI initially have neuroprotective and reparative effects, but prolonged neuroinflammation leads to secondary injury and increases the risk of chronic neurodegenerative diseases. Persistent microglial activation plays a critical role in chronic neuroinflammation post-TBI. Given the bidirectional communication along the brain\u2013gut axis, it is plausible to suppose that gut microbiota dysbiosis post-TBI influences microglial activation. In the present study, hippocampal microglial activation was observed at 7 days and 28 days post-TBI. However, in TBI mice with a depletion of gut microbiota, microglia were activated at 7 days post-TBI, but not at 28 days post-TBI, indicating that gut microbiota contributes to the long-term activation of microglia post-TBI. In addition, in conventional mice colonized by the gut microbiota of TBI mice using fecal microbiota transplant (FMT), microglial activation was observed at 28 days post-TBI, but not at 7 days post-TBI, supporting the role of gut microbiota dysbiosis in persistent microglial activation post-TBI. The RNA sequencing of the hippocampus identified a microglial activation gene, Lyz2, which kept upregulation post-TBI. This persistent upregulation was inhibited by oral antibiotics and partly induced by FMT. 16s rRNA gene sequencing showed that the composition and function of gut microbiota shifted over time post-TBI with progressive dysbiosis, and untargeted metabolomics profiling revealed that the tryptophan metabolic phenotype was differently reshaped at 7 days and 28 days post-TBI, which may play a role in the persistent upregulation of Lyz2 and the activation of microglia. This study implicates that gut microbiota and Lyz2 are potential targets for the development of novel strategies to address persistent microglial activation and chronic neuroinflammation post-TBI, and further investigations are warranted to elucidate the specific mechanism.<\/jats:p>","DOI":"10.3390\/nu14173467","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T23:48:58Z","timestamp":1661384938000},"page":"3467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Gut Microbiota Dysbiosis after Traumatic Brain Injury Contributes to Persistent Microglial Activation Associated with Upregulated Lyz2 and Shifted Tryptophan Metabolic Phenotype"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6433-2421","authenticated-orcid":false,"given":"Zhipeng","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Fourth Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310006, China"},{"name":"Department of Critical Care Medicine, Affiliated Hangzhou First People\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-0786","authenticated-orcid":false,"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Affiliated Hangzhou First People\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Affiliated Hangzhou First People\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Hangzhou First People\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Affiliated Hangzhou First People\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Affiliated Hangzhou First People\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Secondary Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Affiliated Hangzhou First People\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/S1474-4422(18)30469-1","article-title":"Traumatic brain injury in China","volume":"18","author":"Jiang","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S1474-4422(17)30371-X","article-title":"Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research","volume":"16","author":"Maas","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.biopsych.2021.05.025","article-title":"Traumatic Brain Injury and Risk of Neurodegenerative Disorder","volume":"91","author":"Brett","year":"2021","journal-title":"Biol. 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