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

Clinical Snapshot

Key Findings

• P Value: Seizure latency, severity, and duration: statistically significant (p not individually specified in abstract); MDA: p = 0.076 (non-significant); Spatial learning: p < 0.05; Anxiety-like behaviour: p < 0.001

• Effect Size: Seizure latency: MD = +22.09 seconds; Seizure severity: MD = −1.08 (scale units); Seizure duration: MD = −23.19 seconds. IL-1β, IL-6, and TNF-α significantly reduced; MDA showed non-significant trend toward reduction

• Primary Outcome: Probiotic supplementation significantly increased seizure latency and reduced seizure severity and duration in rodent epilepsy models

• Nnt Or Sensitivity: NNT not calculable from preclinical continuous outcome data. No sensitivity/specificity applicable. No hazard ratios reported. Translational NNT for human epilepsy cannot be derived from these preclinical mean differences.

• Confidence Interval: Latency: 95% CI 10.52 to 33.67; Severity: 95% CI −1.39 to −0.76; Duration: 95% CI −35.56 to −10.82

Clinical Application

Probiotic supplementation is generally low-cost, widely available, and has an acceptable safety profile in most populations. However, optimal strain selection, dosing, duration, and formulation for anticonvulsant purposes remain entirely undefined. Standardised pharmaceutical-grade probiotic preparations would be required for clinical trial design. No probiotic preparation is currently listed on the Australian Pharmaceutical Benefits Scheme (PBS) for epilepsy or any neurological indication. The Therapeutic Goods Administration (TGA) regulates probiotics as complementary medicines under the ARTG; claims of anticonvulsant efficacy would require Level I evidence before therapeutic claims could be approved. RACGP guidelines for epilepsy management do not currently include microbiome-based interventions. Australian neurologists and general practitioners should be aware of patient interest in probiotic supplementation for epilepsy but should counsel that no clinical evidence of efficacy exists. The Australian Epilepsy Project and NHMRC-funded microbiome research programs represent potential frameworks for future translational clinical trials in this space. Currently applicable only to preclinical research contexts. Potential future applicability to patients with drug-resistant epilepsy or those seeking adjunctive therapies, particularly where gut dysbiosis is implicated. Paediatric epilepsy populations (e.g., those on ketogenic diet, which itself modulates the microbiome) may represent a future translational target.

Abstract

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 Lactobacillus (e.g., acidophilus, casei, fermentum) and Bifidobacterium 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 (p = 0.076). Behaviorally, improvements in spatial learning (p < 0.05) and reduced anxiety-like behavior (p < 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.

References

1. 1.Simani, L., Hooshmandi, E., Hajisoltani, R., & Hooshmandi, S. (2026). Probiotics and seizure susceptibility in preclinical epilepsy models: mechanistic insights from a systematic review and meta-analysis. Reviews in the Neurosciences. Advance online publication. PubMed ID: 41698855