BackgroundIn the new era, microbial-based medicine is one of the best strategies that try to modify the normal flora with the aim of treating some disorders. This systematic review and meta-analysis was performed to evaluate the use of probiotics in the treatment of the clinical outcomes in cases with traumatic brain injury..MethodsIn this regard, the search strategy was done using databases such as PubMed, Embase, Scopus, CENTRAL, and Google Scholar, from 2006 until April 2024. All studies about the efficacy of probiotic supplementation on the clinical outcomes in traumatic brain injury patients were retrieved. During the assessment process of the eligible studies, we evaluated clinical characteristics such as the Glasgow Coma Scale score, the Sequential Organ Failure Assessment score, the Acute Physiology and Chronic Health Evaluation II score, referral rate and hospitalization period in the intensive care unit, mortality rate, as well as opportunistic infections in both groups of case and control..ResultsIn this study, the authors analyzed data from 6 articles including 391 cases with traumatic brain injury. Our results showed that the probiotic therapy increases the Glasgow Coma Scale score in patients with the average age of more than 50 years. However, there was no a significant difference in the Sequential Organ Failure Assessment and the Acute Physiology and Chronic Health Evaluation scores between the group that had received probiotics and the control group. Although probiotic-based treatment did not significantly affect the intensive care unit admission (or length of stay), but, the risk of infection, and also mortality was significantly lower in the probiotic group (OR: 0.53; 95% CI: 0.3 to 0.8, as well as OR: 0.41; 95% CI: 0.2 to 0.7, respectively)..ConclusionsOverall, due to the modification of microbial flora, probiotic supplements can balance microflora disturbances, which in turn leads to improvement the clinical outcomes in patients with brain injury. Therefore, probiotic-based therapy can be considered as a promising strategy for the treatment of the central nervous system disorders. However, given the limited evidence, more clinical trial studies need to strengthen our results..