Sarah Rice BSc. (Hons), MCOptom (UK), MHP, NNP
It is not surprising that the gastrointestinal tract (GIT) and microbiota are attracting considerable interest in the research field. As the primary interface with the outside world, the GIT is a central hub for nutrient and immune signaling that has bidirectional effects on all body systems. The microbiome consists of approximately 100 trillion microorganisms that inhabit the human gut. These microorganisms, along with the metabolites they generate, interact with human physiology and can affect a wide range of conditions. Commentary on various conditions and their relationship to the microbiome is widespread in the literature and spans metabolic, inflammatory, neurological, and endocrine domains (1, 3).
The microbiome is difficult to study because of its ability to be influenced by a number of factors, which include diet, stress, exercise, age, genetics, and environmental factors (2). Factors that influence the development of a healthy microbiome begin in infancy, and this complexity makes it difficult to define the determinants of a healthy microbiome, although trends are emerging (2). A key feature is that these complex communities, which include bacteria, fungi, protozoa and viruses, interact in a balanced manner, promoting homeostasis (2). Gut dysbiosis, on the other hand, reflects altered populations, which appear to be associated with disease.
One area under investigation is the interaction between ketogenic diet therapy and the microbiome in the treatment of epilepsy. The ketogenic diet has a 100-year history as an effective treatment for epilepsy, and there are a number of mechanisms by which it can exert therapeutic effects. The gut-brain axis is one way in which the microbiome and metabolites found in patients with epilepsy link dysbiosis and seizures. Changes in GABA synthesis and other characteristics of neurotransmission may contribute to lowering the seizure threshold (3). Antibiotics, probiotics, gastroenteritis, and gastroesophageal reflux disease (GERD) have all been associated with seizure episodes, with reductions seen in those taking antibiotics and probiotics (3).
People with epilepsy have been shown to have differences in microbiome characteristics compared to controls, but there is some heterogeneity among the findings. Common themes and proposed pathways emerge from studies showing that the ketogenic diet can improve dysbiosis, increase Bacteroidetes to Firmicutes proportion and increase of groups of bacteria associated with GABA production, mainly Bacteroides, Parabacteroidesand Escherichia (3).
In patients with drug-resistant epilepsy (DRE), the microbiome appears to mediate dietary effects. In a small study, children with DRE showed changes in their microbiome and metabolites that were linked to fewer seizures, particularly an increase in plasmagen-producing bacteria. Plasmagons affect membrane function and associated signaling. they are the main phospholipids in the gray and white matter of the frontal and parietal cortex (4).
By itself, the ketogenic diet will reshape the microbiome, with drug interactions also playing a role in its overall impact on this adaptable community. Two-way signals create layers of complexity. Untangling these issues is an ongoing challenge, and it may take some time before we fully understand their interactions. What we do know is that the Western diet has many features that can promote dysbiosis and affect function, including a tendency to increase levels of endotoxin-producing bacteria. Food processing provides acellular nutrients that affect absorption, and food additives such as emulsifiers can affect the human (host) microbiome and physiology (5).
Finally, the human gut has been shown to be inherently flexible, able to adapt to a wide range of foods, and flexibility may be an indicator of gut health (6). Higher-fat diets, such as the ketogenic diet, rapidly produce adaptations in the microbiome that complement the dietary change. The reduction in complex carbohydrates that gut bacteria metabolize to produce short-chain fatty acids (such as acetate, propionate, and butyrate) may be compensated by the production of a similar metabolite, isobutyrate, as well as differences due to ketone body metabolism. Focusing on a real food or whole food approach remains an important feature of therapeutic carbohydrate reduction. Improvements in gut health often coincide with the orchestra of metabolic changes that occur with this dietary change.
A whole foods, reduced carb approach can work with a range of eating patterns and gut sensitivities. Removing processed foods and replacing them with whole, lower-carb foods allows the two-way pathways of metabolism and gut to work together to improve health. Well-formulated ketogenic diets can provide additional benefits through ketone body metabolism, immune regulation, and gut-brain signaling. Microbiome research remains an exciting but complex field to navigate, with many unanswered questions driving continued research.
The Nutrition Network is launching a new training course: Gut Health: The Microbiome, Metabolism, and Modern Disease. This training examines how industrialized food systems, environmental changes, metabolic dysfunction and modern lifestyles have profoundly altered the ecology of the human gut. Practical frameworks guide clinicians in restoring gut health and promote a deeper understanding of gut-metabolism pathways.
- Mu, C., Rho, JM and Shearer, J. (2025) ‘The interaction between the gut and the ketogenic diet in health and disease’, Advanced Science, 12(36), pp. e04249. Available in:
- Campbell-McBride, N., Rice, SM and Murphy, T. (2023) ‘Chapter 8 – Gastrointestinal health and therapeutic carbohydrate restriction’, in TD Noakes et al. (ed.) Ketogenic. Academic Press, pp. 383–413. Available in:
- Kowalcze, K. et al. (2026) ‘Modulation of Gut Microbiome and Metabolome as One of the Potential Mechanisms of Ketogenic Diet Effect in the Treatment of Epilepsy’, Nutrients, 18(1), p 31. Available at:
- Dahlin, M., Wheelock, CE and Prast-Nielsen, S. (2024) ‘Association between seizure reduction during ketogenic diet treatment of epilepsy and changes in circulating metabolites and gut microbial composition’, eBioMedicine, 109, pp. 105400. Available at:
- Zinöcker, MK and Lindseth, IA (2018) ‘The Western diet-microbe-host interaction and its role in metabolic disease’, Nutrients, 10(3), p 365. Available at: https://doi.org/10.3390/nu10030365.
- Sholl, J., Mailing, LJ and Wood, TR (2021) ‘Reframing Nutritional Microbiota Studies To Reflect an Inherent Metabolic Flexibility of the Human Gut: a Narrative Review Focusing on High-Fat Diets’, mBio, 12(2). Available in:
