Gut Microbiome Disruption in Traumatic Brain Injury and Therapeutic Potential of Probiotics: A Systematic Review and Meta-Analysis.
4 affiliations
- 1Department of Anesthesiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
- 2Agent-Based Modelling Laboratory, Centre of Excellence in AI for Public Health Advancement, York University, Toronto, ON M3J 1P3, Canada.
- 3Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics, Czech Academy of Sciences, 142 00 Prague, Czech Republic.
- 4McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Abstract
Background
Traumatic brain injury (TBI) is increasingly recognized as a systemic disorder that may involve alterations in the brain-gut-microbiome (BGM) axis, a bidirectional network linking the brain, immune system, and gut microbiota. While animal studies suggest that disruption and restoration of the BGM axis influence TBI-related changes and recovery, respectively, human evidence remains fragmented.Methods
MEDLINE, Embase, Scopus, and Web of Science were searched through 2025; Global Health was additionally searched for Aim 2. This study had two aims: (1) to assess gut microbiome changes following TBI and (2) to evaluate the effects of probiotic supplementation in TBI patients. Data were synthesized using random-effects meta-analyses, and risk of bias was assessed using the Newcastle-Ottawa and Cochrane tools.Results
Five studies (Aim 1) and fifteen studies (Aim 2) met the inclusion criteria. TBI was associated with shifts in microbial composition, including reduced abundance of Prevotella (p < 0.001), and Parabacteroides merdae (p = 0.038), whereas overall alpha diversity did not differ significantly. Probiotic supplementation improved neurological outcomes [Glasgow Coma Scale (GCS): MD = 2.25, 95% CI 1.34-3.16, p < 0.001] and functional outcomes [Glasgow Outcome Scale (GOS): MD = 1.40, 95% CI 1.12-1.69, p < 0.001], and reduced inflammatory markers, including TNF-α (p = 0.006), IL-6 (p < 0.001), procalcitonin (p < 0.001), and D-lactic acid levels (p < 0.001). High heterogeneity was observed across several outcomes, with the GOS showing moderate heterogeneity. Neurocognitive outcomes were evaluated qualitatively and were not pooled in a meta-analysis because of limited available data.Conclusions
The findings of this analysis suggest that TBI is associated with alterations in the gut microbiome and that microbiota-targeted therapies involving probiotics may improve inflammatory, gut-barrier, neurological, and functional outcomes. Although substantial heterogeneity was observed across several outcomes, particularly the GCS, the available evidence supports further investigation of microbiome-directed interventions as adjunctive strategies for TBI management. Standardized multicenter trials are warranted.Prospero
CRD420251135998.
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BibTeX
@article{khan2026microbiome,
title = {{Gut Microbiome Disruption in Traumatic Brain Injury and Therapeutic Potential of Probiotics: A Systematic Review and Meta-Analysis.}},
author = {Zeeshan A Khan and Zara Chowdhury and Riya Modi and Dewan Md Sumsuzzman and Ling-Sha Ju and Rajendra K Labala and Nikolaus Gravenstein and Anatoly E Martynyuk},
journal = {Biology},
year = {2026},
month = oct,
doi = {10.3390/biology15191730},
url = {https://europepmc.org/article/MED/42883403},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gut Microbiome Disruption in Traumatic Brain Injury and Therapeutic Potential of Probiotics: A Systematic Review and Meta-Analysis.
AU - Zeeshan A Khan
AU - Zara Chowdhury
AU - Riya Modi
AU - Dewan Md Sumsuzzman
AU - Ling-Sha Ju
AU - Rajendra K Labala
AU - Nikolaus Gravenstein
AU - Anatoly E Martynyuk
PY - 2026
DA - 2026/10/01
JO - Biology
DO - 10.3390/biology15191730
UR - https://europepmc.org/article/MED/42883403
AB - Background Traumatic brain injury (TBI) is increasingly recognized as a systemic disorder that may involve alterations in the brain-gut-microbiome (BGM) axis, a bidirectional network linking the brain, immune system, and gut microbiota. While animal studies suggest that disruption and restoration of the BGM axis influence TBI-related changes and recovery, respectively, human evidence remains fragmented.Methods MEDLINE, Embase, Scopus, and Web of Science were searched through 2025; Global Health was additionally searched for Aim 2. This study had two aims: (1) to assess gut microbiome changes following TBI and (2) to evaluate the effects of probiotic supplementation in TBI patients. Data were synthesized using random-effects meta-analyses, and risk of bias was assessed using the Newcastle-Ottawa and Cochrane tools.Results Five studies (Aim 1) and fifteen studies (Aim 2) met the inclusion criteria. TBI was associated with shifts in microbial composition, including reduced abundance of Prevotella (p < 0.001), and Parabacteroides merdae (p = 0.038), whereas overall alpha diversity did not differ significantly. Probiotic supplementation improved neurological outcomes [Glasgow Coma Scale (GCS): MD = 2.25, 95% CI 1.34-3.16, p < 0.001] and functional outcomes [Glasgow Outcome Scale (GOS): MD = 1.40, 95% CI 1.12-1.69, p < 0.001], and reduced inflammatory markers, including TNF-α (p = 0.006), IL-6 (p < 0.001), procalcitonin (p < 0.001), and D-lactic acid levels (p < 0.001). High heterogeneity was observed across several outcomes, with the GOS showing moderate heterogeneity. Neurocognitive outcomes were evaluated qualitatively and were not pooled in a meta-analysis because of limited available data.Conclusions The findings of this analysis suggest that TBI is associated with alterations in the gut microbiome and that microbiota-targeted therapies involving probiotics may improve inflammatory, gut-barrier, neurological, and functional outcomes. Although substantial heterogeneity was observed across several outcomes, particularly the GCS, the available evidence supports further investigation of microbiome-directed interventions as adjunctive strategies for TBI management. Standardized multicenter trials are warranted.Prospero CRD420251135998.
SN - 2079-7737
ER -