Neurotrauma and the Gut–Brain Axis: Mechanistic Insights and Therapeutic Implications

Abstract The gut–brain axis (GBA) represents a complex bidirectional communication network linking the gastrointestinal tract and the central nervous system through neural, immune, endocrine, and metabolic pathways. Increasing evidence indicates that traumatic brain injury (TBI) and spinal cord injury (SCI) disrupt gut microbial homeostasis, resulting in dysbiosis, increased intestinal permeability, systemic inflammation, and secondary neurological injury. Alterations in microbial composition, depletion of short-chain fatty acid–producing bacteria, and dysregulated immune signaling contribute to neuroinflammation and multisystem dysfunction following neurotrauma. Experimental studies highlight the role of microbial metabolites, inflammatory mediators, enteroendocrine signaling, and vagal pathways in modulating neurological outcomes. Emerging therapeutic strategies targeting the GBA, including probiotics, prebiotics, dietary modification, short-chain fatty acid supplementation, fecal microbiota transplantation, amino acid supplementation, and judicious antibiotic use have shown promise in attenuating inflammation and supporting recovery. However, robust clinical evidence remains limited. This narrative review synthesizes current knowledge on the pathophysiological mechanisms linking the gut and brain in neurotrauma, evaluates existing and emerging therapeutic interventions, and identifies key gaps in knowledge that must be addressed to translate microbiome-based strategies into effective clinical therapies.