Probiotics and Seizure Susceptibility: A Systematic Review and Meta-Analysis of Preclinical Epilepsy Models

Background The gut microbiota can affect neuronal excitability, inflammation, and oxidative balance via the gut-brain axis, shaping seizure susceptibility. To translate these mechanistic findings into practical clinical approaches, we need a synthesis of preclinical evidence on microbiome-based interventions. Objective A systematic review and meta-analysis to examine probiotics' putative anticonvulsant, anti-inflammatory, antioxidant, and neuroprotective properties in rodent models. Methods An extensive, systematic search of online databases was conducted up to July 2025 to identify eligible animal studies in which probiotics were administered in seizure models. Reported outcomes included seizure latency, duration, severity, and frequency, as well as inflammation, oxidative stress, and behavioral measures. Where necessary, outcome data were standardized across studies before pooling. Results Of the 24 studies that met the inclusion criteria, 19 provided sufficient data to be included in the meta-analysis. Probiotics significantly increased seizure latency (MD = 22.09; 95%CI: 10.52 to 33.67), and reduced seizure severity (MD= -1.08; 95%CI: −1.39 to − 0.76) and duration (MD= -23.19; 95%CI: −35.56 to − 10.82). Probiotics significantly reduced IL-1β, IL-6, and TNF-α levels while MDA showed a non-significant trend toward reduction (p = .076). Behaviorally, improvements in spatial learning (p < 0.05) and reduced anxiety-like behavior (p < 0.001) were observed. Conclusion Probiotic supplementation appears to exert anticonvulsant, anti-inflammatory, antioxidant, and behavioral benefits in preclinical epilepsy models, although the evidence is heterogeneous and limited to animal studies. Mechanistic evidence indicates modulation of the gut–brain axis, enhanced GABAergic signaling, and improved mitochondrial function. These findings support further investigation of specific probiotic formulations as promising adjunct candidates in well-designed, mechanism-driven clinical trials.