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However, these data did not determine if the impact of antibiotic exposure on the brain's response to injury was mediated directly by antibiotics or indirectly via modulation of the gut microbiota. We designed two different approaches to address this knowledge gap. One was utilizing fecal microbiota transplantation (FMT) from control and antibiotic-treated mice (treated with vancomycin, neomycin, ampicillin, and metronidazole [VNAM]) into germ-free (GF) mice prior to injury, and the other was exposing specific pathogen-free (SPF) mice to a 2-week period of antibiotics prior to injury but discontinuing antibiotics 72\u2009h prior to injury. GF mice receiving FMT from VNAM-treated mice (GF-VNAM) demonstrated reduced gut bacterial alpha diversity and richness compared with GF mice receiving control FMT. At 7 days post-injury, GF-VNAM had increased microglial activation, reduced infiltration of T cells, and decreased neurogenesis. Similarly, SPF mice exposed to antibiotics prior to but not after injury demonstrated similar alterations in neuroinflammation and neurogenesis compared with control mice. These data support our hypothesis implicating the gut microbiota as an important modulator of the neuroinflammatory process and neurogenesis after TBI and provide an exciting new approach for neuroprotective therapeutics for TBI.<\/jats:p>","DOI":"10.1089\/neu.2022.0356","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T05:36:17Z","timestamp":1666157777000},"page":"772-787","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Innate and Peripheral Immune Alterations after Traumatic Brain Injury Are Regulated in a Gut Microbiota-Dependent Manner in Mice"],"prefix":"10.1177","volume":"40","author":[{"given":"Marta","family":"Celorrio","sequence":"first","affiliation":[{"name":"Department of Pediatrics, and Division of Infectious Diseases, Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill","family":"Shumilov","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and Division of Infectious Diseases, Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Rodgers","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Schriefer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan T.","family":"Baldridge","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart H.","family":"Friess","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and Division of Infectious Diseases, Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.10.027"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2974"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3430"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2876"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0332-7"},{"key":"e_1_3_5_7_2","doi-asserted-by":"crossref","unstructured":"Erny D Hrabe de Angelis AL Jaitin D et al. 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