Probiotics and seizure susceptibility in preclinical epilepsy models: mechanistic insights from a systematic review and meta-analysis

The gut microbiota can affect neuronal excitability, inflammation, and oxidative balance via the gut-brain axis, shaping seizure susceptibility. To translate these findings into clinical approaches, a synthesis of preclinical microbiome-based evidence is needed. This systematic review and meta-analysis examined the putative anticonvulsant, anti-inflammatory, antioxidant, and neuroprotective effects of probiotics in rodent models. An extensive systematic search up to July 2025 identified 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. Of the 24 studies that met the inclusion criteria, 19 provided sufficient data to be included in the meta-analysis. The most frequently used strains belonged to the <i>Lactobacillus</i> (e.g., acidophilus, casei, fermentum) and <i>Bifidobacterium</i> genera (e.g., bifidum, longum), with occasional synbiotic combinations. 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 nonsignificant trend toward reduction (<i>p</i> = 0.076). Behaviorally, improvements in spatial learning (<i>p</i> < 0.05) and reduced anxiety-like behavior (<i>p</i> < 0.001) were observed. 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.