Epilepsy, Ketogenic Diet, and Gut Microbiota: Implications for Clinical Nutrition - A Systematic Review

Vicente M. Martinez Cardenas, Vivian R. Mena Miranda

Abstract: Background: Ketogenic diet therapy is an established nonpharmacological treatment for drug-resistant epilepsy. Experimental and clinical evidence suggests that diet-induced changes in the intestinal microbiome may influence seizure susceptibility and treatment response, but the direction and clinical significance of these changes remain incompletely defined. Objective: To synthesize primary evidence published from 2018 through March 31, 2026 concerning the relationships among ketogenic diet therapy, the gut microbiota, seizure outcomes, and clinically relevant nutritional effects. Methods: A systematic review was conducted in accordance with PRISMA 2020. PubMed/MEDLINE, Scopus, and Web of Science were searched for original human and animal studies. Eligible studies evaluated at least two components of the epilepsy-ketogenic diet-gut microbiota relationship and reported microbiological, metabolomic, seizure, or nutrition-related outcomes. Two reviewers independently performed study selection and data extraction. Human observational studies were appraised with design-appropriate Joanna Briggs Institute tools, and animal studies with the SYRCLE risk-of-bias tool. Owing to marked clinical and methodological heterogeneity, findings were synthesized narratively. Results: Fourteen primary studies were included: seven human or translational studies and seven animal studies. Pediatric studies consistently showed that ketogenic diet therapy altered microbial composition or function, but taxonomic findings were heterogeneous. Several studies reported reduced microbial diversity, lower bifidobacterial abundance, or reduced fecal short-chain fatty acids, whereas others identified baseline microbial or inflammatory signatures associated with treatment response. In mechanistic models, microbiota depletion, microbial transfer, probiotic manipulation, diet withdrawal, and variation in dietary fiber modified seizure susceptibility or ketogenic diet effects. Transfer of post-ketogenic-diet microbiota from children with refractory epilepsy increased seizure resistance in recipient mice. However, most human studies were small, nonrandomized, and unable to establish microbiota-mediated causality. Conclusions: Ketogenic diet therapy reproducibly modifies the intestinal microbiome, and experimental evidence supports a contributory role of microbial and metabolic pathways in seizure protection. Human evidence remains preliminary and does not justify microbiome-based treatment selection or routine probiotic supplementation. Clinical nutrition protocols should preserve seizure control while monitoring gastrointestinal symptoms, growth, micronutrient adequacy, fiber intake, and metabolic complications. Larger prospective studies with standardized diet formulations, microbiome methods, and seizure outcomes are required.

Keywords: drug-resistant epilepsy, ketogenic diet, gut microbiota, gut-brain axis, short-chain fatty acids, clinical nutrition, seizures

How to Cite?: Vicente M. Martinez Cardenas, Vivian R. Mena Miranda, "Epilepsy, Ketogenic Diet, and Gut Microbiota: Implications for Clinical Nutrition - A Systematic Review", Volume 15 Issue 8, August 2026, International Journal of Science and Research (IJSR), Pages: 1397-1407, https://www.ijsr.net/getabstract.php?paperid=SR26818174812, DOI: https://dx.doi.org/10.21275/SR26818174812

Download Citation: APA | MLA | BibTeX | EndNote | RefMan