Gut Microbial Dysbiosis after Traumatic Brain Injury Induces Alterations in the Immune Response and Fear Memory

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, microbial dysbiosis after TBI reduced hippocampal infiltration of Ly6Chigh monocytes followed by a decreased presence of CD4+ and CD8+ T cells that persisted through 1 month post-injury, and increase of microglial pro-inflammatory markers. By 3 months, these mice had a larger percentage of microglia with a persistent amoeboid morphology, increased neuronal loss, and a maladaptive fear memory response. These data demonstrate the important role the gut microbiota plays in neuroinflammation and recovery after TBI and implicate gut microbial modulation as a potential therapeutic intervention.