Modulation of Gut Microbiome and Metabolome as One of the Potential Mechanisms of Ketogenic Diet Effect in the Treatment of Epilepsy

Sep 30, 2026

Ketogenic diet (KD) used for more than a century in epilepsy has established therapeutic value, while emerging evidence links its benefits to changes in gut microbiome and metabolome and to how these changes track seizure course. This narrative review synthesizes published findings on how KD’s antiepileptic effects may operate via microbiome–metabolome modulation. Findings indicate KD can alter intestinal bacteria and metabolites, improve dysbiosis, reduce intestinal and systemic inflammation, influence neurochemistry and metabolic pathways, and promote metabolites such as short-chain fatty acids.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages32

Reading Time1 h 21 min

AccessFree to download

Abstract

Background/Objectives

Methods

Results

Conclusions

Introduction

Review Modulation of Gut Microbiome and Metabolome as One of the Potential Mechanisms of Ketogenic Diet Effect in the Treatment of Epilepsy Katarzyna Kowalcze 1,2,†, Damian Dy ´nka 1,†, Wiktoria Klus 3, Magdalena Dudzi ´nska 4 and Agnieszka Paziewska 1,3, * Academic Editor: JoseM. Soriano del Castillo Received: 19 November 2025 Revised: 12 December 2025 Accepted: 16 December 2025 Published: 21 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Institute of Health Sciences, Faculty of Medical and Health Sciences, University of Siedlce, 08-110 Siedlce, Poland; [katarzyna.kowalcze@uws.edu.pl](katarzyna.kowalcze@uws.edu.pl) (K.K.); [damian.dynka@uws.edu.pl](damian.dynka@uws.edu.pl) (D.D.) 2 Sirene Medical Clinic, 02-796 Warszawa, Poland 3 Warsaw Genomics S.A., 02-089 Warsaw, Poland; [wiktoria.klus@onet.com.pl](wiktoria.klus@onet.com.pl) [4](4 Pediatric Neurology Department)[ Pediatric Neurology Department](4 Pediatric Neurology Department), [Chorzow General Hospital](Chorzow General Hospital), [41-500 Chorz](41-500 Chorz)ó[w](w), [Poland](Poland); [mdudzinskapl@gmail.com](mdudzinskapl@gmail.com) * Correspondence: [agnieszka.paziewska@uws.edu.pl](agnieszka.paziewska@uws.edu.pl)[ ](agnieszka.paziewska@uws.edu.pl)† These authors contributed equally to this work. Abstract Background/Objectives: The over 100-year-old practice of using ketogenic diet (KD) in the treatment of epilepsy has consolidated its position as an effective therapeutic tool. The available publications suggest a significant influence of KD on gut microbiome and metabolome and, on the other hand, a correlation between microbiome and metabolome changes and the course of epilepsy. The conclusion is therefore justified that KD can exert a therapeutic effect in epilepsy through the mechanism of gut microbiome and metabolome modulation. Methods:This article is a narrative review aimed at a comprehensive analysis of the literature to gather existing evidence on the relationship between ketogenic diet, its antiepileptic effects and modulation of gut microbiome and metabolome. Results: It has been demonstrated that a ketogenic diet exerts a significant effect on intestinal bacteria and their metabolites, among other actions, increasing the Bacteroides to Firmicutes (B/F) ratio, alleviating dysbiosis, reducing the inflammatory condition in the gut and whole body, increasing the number of specific strains associated with antiepileptic effect, mediating the production of neurotransmitters (GABA, serotonin), exerting influence on the dopaminergic system, on a number of metabolic pathways, on inhibition of genotoxicity and production of short-chain fatty acids (SCFA) in the intestine. Conclusions: Further studies are needed, since the effect of KD on gut microbiome and metabolome modulation in the treatment of epilepsy is an extremely promising and trendsetting direction of research. Keywords: epilepsy; neurological diseases; neurology; microbiome; metabolome; microbiota; modulation; ketogenic diet; metabolites; intestines; intestinal bacteria; treatment 1. Introduction The widespread occurrence of epilepsy significantly influences the quality of life of millions of people (mainly children) worldwide. That prompts researchers to conduct increasing numbers of studies and to publish papers on the treatment, pathophysiology, classification, or epidemiology of that disease [1,2] . One of the leading research areas in this respect is the therapeutic, antiepileptic effect of the ketogenic diet. It has been used with high effectiveness in the treatment of epilepsy for over 100 years, since an article by Wilder was published in the year 1921 [3] . Despite the high effectiveness of that treatment method, its mechanisms of action still have not been unequivocally confirmed. One of the p

FAQs

What is the main proposed mechanism linking ketogenic diet to epilepsy treatment?

The review proposes that KD can exert therapeutic effects through modulation of the gut microbiome and metabolome, which may also influence the gut–brain axis relevant to epilepsy.

What evidence does the review highlight from the literature?

It reports that KD affects intestinal bacteria and metabolites, alleviates dysbiosis, reduces gut and systemic inflammatory conditions, and influences metabolite production and metabolic pathways associated with antiepileptic effects.

Why does the review call for further studies?

It states that additional research is needed because the relationship between KD-induced microbiome and metabolome modulation and epilepsy outcomes is a highly promising but still developing research direction.

Sep 30, 2026

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