Beyond Ketosis: Dietary Therapies and the Microbiota-Gut-Brain Axis in Epilepsy

Background: Epilepsy is a complex neurological disorder in which growing evidence supports a significant role for the microbiota-gut-brain axis (MGBA) in modulating neuroinflammation, neuronal excitability, and treatment responsiveness. Beyond their traditional role in inducing ketosis, dietary therapies may influence epilepsy by modulating gut microbial ecology, intestinal barrier integrity, immune signaling, and microbiota-derived metabolites. Methods: This narrative review critically examines current clinical and experimental evidence regarding the relationship between epilepsy, gut microbiota, and dietary interventions. Particular attention was given to ketogenic dietary therapies, the Modified Atkins Diet (MAD), low-glycemic-index treatment (LGIT), Mediterranean dietary patterns, restrictive diets, and microbiota-targeted supplementation, including probiotics, prebiotics, and postbiotics. Results: Available evidence suggests that patients with epilepsy exhibit alterations in gut microbial composition associated with impaired short-chain fatty acid production, intestinal inflammation, and altered neuroimmune regulation. Ketogenic and microbiota-supportive dietary approaches may modulate these pathways beyond ketosis alone, potentially contributing to seizure reduction through integrated metabolic, inflammatory, and microbial mechanisms. Emerging evidence also supports a role for probiotics, prebiotics, and postbiotics in modulating gut-brain communication and neuroinflammatory signaling, although current clinical data remain limited. Conclusions: Dietary therapies in epilepsy should no longer be viewed exclusively as metabolic interventions aimed at inducing ketosis, but rather as potential modulators of the microbiota-gut-brain axis and neuroimmune homeostasis. While further mechanistic and clinical studies are needed, microbiota-targeted nutritional approaches may represent valuable complementary strategies to be integrated alongside conventional antiseizure therapies within more personalized models of epilepsy management.