@article{cd4f039d382b40b6939dfc0e874ae859,
title = "Gut microbial dysbiosis after traumatic brain injury modulates the immune response and impairs neurogenesis",
abstract = "The influence of the gut microbiota on traumatic brain injury (TBI) is presently unknown. This knowledge gap is of paramount clinical significance as TBI patients are highly susceptible to alterations in the gut microbiota by antibiotic exposure. Antibiotic-induced gut microbial dysbiosis established prior to TBI significantly worsened neuronal loss and reduced microglia activation in the injured hippocampus with concomitant changes in fear memory response. Importantly, antibiotic exposure for 1 week after TBI reduced cortical infiltration of Ly6Chigh monocytes, increased microglial pro-inflammatory markers, and decreased T lymphocyte infiltration, which persisted through 1 month post-injury. Moreover, microbial dysbiosis was associated with reduced neurogenesis in the dentate gyrus 1 week after TBI. By 3 months after injury (11 weeks after discontinuation of the antibiotics), we observed increased microglial proliferation, increased hippocampal neuronal loss, and modulation of fear memory response. These data demonstrate that antibiotic-induced gut microbial dysbiosis after TBI impacts neuroinflammation, neurogenesis, and fear memory and implicate gut microbial modulation as a potential therapeutic intervention for TBI.",
keywords = "Antibiotics, Fear conditioning, Gut microbial dysbiosis, Microglia, Monocytes, Neurogenesis, T cells, Traumatic brain injury",
author = "Marta Celorrio and Abellanas, {Miguel A.} and James Rhodes and Victoria Goodwin and Jennie Moritz and Sangeetha Vadivelu and Leran Wang and Rachel Rodgers and Sophia Xiao and Ilakkia Anabayan and Camryn Payne and Perry, {Alexandra M.} and Baldridge, {Megan T.} and Aymerich, {Maria S.} and Ashley Steed and Friess, {Stuart H.}",
note = "Funding Information: This work was supported by the National Institutes of Health (R01NS097721). This study was also supported by an educational grant issued by Boehringer–Ingelheim, Germany. Fluorescent imaging was performed on a Zeiss Axio Imager Z2 Fluorescence Microscope with ApoTome 2 optical sectioning grid imager through the use of Washington University Center for Cellular Imaging (WUCCI) supported by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015-505 and CDI-CORE-2019-813) and the Foundation for Barnes-Jewish Hospital (3770 and 4642). Confocal imaging was generated on a Zeiss LSM 880 Airyscan Confocal Microscope which was purchased with support from the Office of Research Infrastructure Programs (ORIP), a part of the NIH Office of the Director under grant OD021629. Funding Information: This work was supported by the National Institutes of Health (R01NS097721). This study was also supported by an educational grant issued by Boehringer–Ingelheim, Germany. Fluorescent imaging was performed on a Zeiss Axio Imager Z2 Fluorescence Microscope with ApoTome 2 optical sectioning grid imager through the use of Washington University Center for Cellular Imaging (WUCCI) supported by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015-505 and CDI-CORE-2019-813) and the Foundation for Barnes-Jewish Hospital (3770 and 4642). Confocal imaging was generated on a Zeiss LSM 880 Airyscan Confocal Microscope which was purchased with support from the Office of Research Infrastructure Programs (ORIP), a part of the NIH Office of the Director under grant OD021629. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1186/s40478-021-01137-2",
language = "English",
volume = "9",
journal = "Acta Neuropathologica Communications",
issn = "2051-5960",
number = "1",
}