{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:53:18Z","timestamp":1791003198671,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01HD107722"],"award-info":[{"award-number":["R01HD107722"]}]},{"name":"National Institutes of Health","award":["R56HD102898"],"award-info":[{"award-number":["R56HD102898"]}]},{"name":"I. Heerman Anesthesia Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Background: Traumatic brain injury (TBI) is increasingly recognized as a systemic disorder that may involve alterations in the brain\u2013gut-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\u2013Ottawa 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 &lt; 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\u20133.16, p &lt; 0.001] and functional outcomes [Glasgow Outcome Scale (GOS): MD = 1.40, 95% CI 1.12\u20131.69, p &lt; 0.001], and reduced inflammatory markers, including TNF-\u03b1 (p = 0.006), IL-6 (p &lt; 0.001), procalcitonin (p &lt; 0.001), and D-lactic acid levels (p &lt; 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. 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