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CC BY 4.0 · Indian Journal of Neurotrauma 2025; 22(02): 111-121
DOI: 10.1055/s-0045-1807265
Review Article

Role of the Gut-Brain Axis in Severe Traumatic Brain Injury: Insights from Experimental Models and Clinical Studies

Venencia Albert
1   Department of Laboratory Medicine, Jai Prakash Narayan Apex Trauma Center, All India Institute of Medical Sciences, New Delhi, India
,
Arulselvi Subramanian 
1   Department of Laboratory Medicine, Jai Prakash Narayan Apex Trauma Center, All India Institute of Medical Sciences, New Delhi, India
,
Deepak Agrawal 
2   Department of Neurosurgery & Gamma-Knife, All India Institute of Medical Sciences, New Delhi, India
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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


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Artikel online veröffentlicht:
04. April 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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