TY - JOUR AU - Albert, Venencia; Subramanian, Arulselvi; Agrawal, Deepak TI - Role of the Gut-Brain Axis in Severe Traumatic Brain Injury: Insights from Experimental Models and Clinical Studies SN - 0973-0508 SN - 2213-3739 PY - 2025 JF - Indian Journal of Neurotrauma LA - EN VL - 22 IS - 02 SP - 111 EP - 121 DA - 2025/04/04 KW - traumatic brain injury KW - gut microbiome KW - dysbiosis KW - neuroinflammation KW - gut-brain axis KW - microbiome-based interventions AB - 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. PB - Thieme Medical and Scientific Publishers Pvt. Ltd. DO - 10.1055/s-0045-1807265 UR - http://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0045-1807265 ER -