Gut Microbiome Disruption in Traumatic Brain Injury and Therapeutic Potential of Probiotics: A Systematic Review and Meta-Analysis.

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.