Abstract
Traumatic brain injury (TBI) induces systemic alterations, including gut microbiome
dysbiosis, increased intestinal permeability, and neuroinflammatory responses. This
review explores the bidirectional gut-brain interactions, focusing on microbiome alterations,
systemic inflammation, and potential therapeutic interventions. A comprehensive review
of preclinical and human studies was conducted to assess gut microbiota changes following
TBI. Key findings on microbial shifts, gut permeability, neuroinflammatory markers,
and therapeutic strategies were analyzed. Experimental animal models demonstrate that
TBI leads to gut microbiota dysbiosis, loss of short-chain fatty acid-producing bacteria,
and increased bacterial translocation due to impaired intestinal barrier function.
These alterations exacerbate neuroinflammatory cascades, including microglial activation,
cytokine release, and oxidative stress. Dysbiosis-induced metabolic shifts influence
tryptophan metabolism and kynurenine pathway activation, contributing to excitotoxicity
and neurodegeneration. Human studies reveal persistent microbiota imbalances in severe
TBI patients, correlating with systemic inflammation and prolonged recovery. Despite
growing evidence linking gut microbiome alterations to neuroinflammation and secondary
brain injury, challenges remain in translating preclinical findings to clinical applications.
Heterogeneity in experimental models, variability in microbiome assessment techniques,
and gaps in mechanistic understanding hinder standardization. Emerging microbiome-targeted
therapies, including probiotics, offer promising avenues for modulating systemic inflammation
and improving neurological recovery post-TBI. Further research is needed to establish
causal relationships, optimize therapeutic strategies, and evaluate long-term outcomes.
Keywords
traumatic brain injury - gut microbiome - dysbiosis - neuroinflammation - gut-brain
axis - microbiome-based interventions
