Gut microbial dysbiosis after traumatic brain injury modulates the immune response and impairs neurogenesis
Marta Celorrio, Miguel Angel Abellanas, James Rhodes, Victoria M. Goodwin, Jennie Moritz, Sangeetha Vadivelu, Leran Wang, Rachel Rodgers, Sophia Xiao, Ilakkia Anabayan, Camryn Payne, Alexandra Perry, Megan T. Baldridge, Maria S. Aymerich, Ashley Steed, Stuart H. Friess
Abstract
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 Ly6C high 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.