Gut microbial dysbiosis after traumatic brain injury modulates the immune response and impairs neurogenesis

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 establishe...

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Autores: Celorrio, M. (Marta)|||/items/1c21ed29-2398-4b36-9da9-ceee1b049605, Abellanas-Sánchez, M.A. (Miguel Ángel)|||/items/007133d0-5288-468d-b322-6dac2e55713e, Rhodes, J. (James)|||/items/2f516455-6d36-4dd7-8692-65e93469628e, Goodwin, V. (Victoria)|||/items/9cf47818-916d-4bc3-9aaf-6cf4b943024b, Moritz, J. (Jennie)|||/items/41e5b6d6-ef64-49ae-a070-7aaadaf69ea9, Vadivelu, S. (Sangeetha)|||/items/8c3d8df8-a865-486a-9a0d-03fda9498bb5, Wang, L. (Leran)|||/items/379528a9-7813-47ed-8673-cc52ee56f80f, Rodgers, R. (Rachel)|||/items/af840211-4eea-48ec-8375-8b598abebe71, Xiao, S. (Sophia)|||/items/7f73dfb6-b0d8-4524-8d1f-ee807863e31c, Anabayan, I. (Ilakkia)|||/items/8479018d-f761-4e8a-b86b-ca5571023b16, Payne, C. (Camryn)|||/items/15670357-f607-47eb-9a8c-2507960d05dc, Perry, A.M. (Alexandra M.)|||/items/3ead2fa5-6f96-4316-98ae-96609540fa43, Baldridge, M.T. (Megan T.)|||/items/009fc443-c0d5-4420-b072-db477c000aa1, Aymerich-Soler, M.S. (María Soledad)|||/items/f65ae32b-d1a8-4fa4-ba9f-b8b10241f470, Steed, A. (Ashley)|||/items/56340a2f-1c43-475a-8098-7d82cb001195, Friess, H. (Helmut)|||/items/7e18c499-9b12-4978-8af5-e6783a789107
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/115638
Acceso en línea:https://hdl.handle.net/10171/115638
Access Level:acceso abierto
Palabra clave:Antibiotics
Fear conditioning
Gut microbial dysbiosis
Microglia
Monocytes
Neurogenesis
T cells
Traumatic brain injury
Descripción
Sumario: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.

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