Gut Microbiome Influences The Neuroinflammatory Response To Traumatic Brain Injury

Abstract Background: Traumatic brain injury (TBI) is a systemic injury that disrupts a complex arrangement of interacting cells in the brain and in the gastrointestinal tract (GI). Disruption in the brain results in neuroinflammation, in which microglia are a central component along with cytokines and other soluble factors [pro and anti-inflammatory microglia (M1:M2)]. Disruption in the GI due to TBI results in a systemic inflammation which is dependent upon the gut microbiome (GM). Gut microbiome can influence microglia in the brain via the gut-brain axis. In order to determine if the microbiome-microglia connections via the gut-brain axis can be modulated, we used probiotics and antibiotics in a rodent TBI model to evaluate the microbiome-microglial connections in acute and chronic experiments.Methods: The temporal effects of treatment (probiotics or antibiotics) were used to evaluate the gut-associated lymphoid tissue (GALT) influence on the microglial response at 72 hours or 21 days after a cortical contusion injury (CCI), a rodent model of TBI. Injured animals received daily probiotics, antibiotics, or no treatment. Sham-injured animals (controls) did not receive any treatment.Results: Twenty-one days of probiotic treatment attenuated the pro-inflammatory response of microglia (M1:M2) after CCI. The post-injury inflammatory response was heightened in the GALT with antibiotic-induced dysbiosis which resulted in amplification of the pro-inflammatory microglial response. Conclusions: Probiotic treatment after TBI is a potential therapeutic in attenuating microglial activation through anti-inflammatory signaling.