Short-chain fatty acids are a key mediator of gut microbial regulation of T cell trafficking and differentiation after traumatic brain injury

Abstract

The gut microbiota has emerged as a pivotal regulator of host inflammatory processes after traumatic brain injury (TBI). However, the mechanisms by which the gut microbiota communicates to the brain in TBI are still under investigation. We previously reported that gut microbiota depletion (GMD) using antibiotics after TBI resulted in increased microglial activation, reduced neurogenesis, and reduced T cell infiltration. In the present study, we have demonstrated that intestinal T cells contribute to the pool of cells infiltrating the brain after TBI. Depletion or genetic deletion of T cells before injury reversed GMD induced reductions in post-TBI neurogenesis. Short-chain fatty acid supplementation increased T regulatory and T helper 1 cell infiltration to the brain along with restoring neurogenesis and microglia activation after TBI with GMD. These data suggest that T cell subsets are essential cellular mediators by which the gut microbiota modulates TBI pathogenesis, a finding with important therapeutic implications.

Keywords: Gut microbiome; Gut microbiota depletion; Gut-brain axis; Microglia; Neurogenesis; Neuroinflammation; Short-chain fatty acids; T cell-trafficking; T cells; Traumatic brain injury.