The Gut Microbiota-Epilepsy Axis: Bibliometric Trends, Mechanistic Insights, and Microbiota-Targeted Next-Generation Therapeutic Opportunities.

Abstract

Epilepsy is a complex neurological disorder with diverse underlying causes. Growing evidence suggests that gut dysbiosis may promote epileptogenesis by disrupting short-chain fatty acids, tryptophan-kynurenine metabolism, immune signaling, and neuronal excitability. In this review, we combine findings from human and animal studies to explain how gut dysbiosis may influence seizures through the gut-brain axis. We highlight emerging and less-discussed mechanisms, including vagus nerve signaling, microbial amyloids, bacterial extracellular vesicles (BEVs), the queuosine salvage pathway, and multi-kingdom microbiota interactions. We also summarize microbiota profiling studies and describe dysbiosis patterns linked to seizure. To support translation, we propose a peri-ictal multi-omics strategy for biomarker discovery. This includes standardized sampling and integration of metagenomics, metabolomics, and host transcriptomics. In addition, our bibliometric analysis further shows rapidly growing global interest in this topic. Recent studies increasingly focus on the gut-brain axis, ketogenic diet, and inflammation-driven mechanisms. Finally, we outline both established approaches and emerging next-generation microbiome-based therapeutic strategies, including SCFA-restoring synbiotics, engineered psychobiotics, bacteriophage therapy, and AI-guided personalization. These advances highlight the microbiota as modifiable target for adjunctive epilepsy management and provide a translational roadmap for future mechanistically informed research and clinical interventions.