S. Zouganeli, EK. Mitsou, M. Yannakoulia, E. Intze, KC. Mountzouris, S. Fessatou, A. Attilakos, A. Kyriacou, et al. (2026). Gut microbiota shifts and short-chain fatty acids alterations in pediatric epilepsy patients on a Mediterranean ketogenic diet. Epileptic disorders : international epilepsy journal with videotape. https://doi.org/10.1002/epd2.70269

PubMed 42096323

[Abstract]
OBJECTIVE: The olive oil-based Mediterranean ketogenic diet (MedKD) may support patients with drug-resistant epilepsy (DRE) or neurometabolic disorders by integrating ketogenic therapy with the cardiometabolic and neuroprotective advantages of the Mediterranean diet. This study assessed alterations in gut microbiota composition and short-chain fatty acids (SCFAs) in Greek pediatric epilepsy patients under a 3-month MedKD.

METHODS: Patients eligible for ketogenic diet therapy and one parent per patient as controls were enrolled. An olive oil-based KD aligned with Mediterranean principles was initiated during a 5-7-day hospital stay. Anthropometric, nutritional, biochemical and clinical data were recorded at baseline and after 3 months. Fecal samples were collected from patients at both time points, and parents provided a single baseline sample. Microbiota composition was analyzed using 16S rRNA gene next-generation sequencing, and SCFAs were quantified via gas chromatography. Written informed consent was obtained from all parents. The study was registered at ClinicalTrials.gov (NCT05898438).

RESULTS: The study enrolled 18 pediatric/adolescent patients (aged 2.5-15.5 years) and 17 parents at baseline (T1). After 3 months (T2), 13 patient-parent pairs completed follow-up. MedKD adherence was high, with mean ketone levels of 2.6 mmol/L and a clinical response in 85% of patients. Anthropometric measurements improved, and lipid changes were modest. No significant α-diversity differences were detected between patients and parents at T1 or between T1 and T2 in patients, whereas β-diversity differed significantly between parents and patients at baseline. Epilepsy-associated genera were more abundant in patients. At T2, patients exhibited shifts including increased members of Eggerthellaceae and decreased Lachnospira and Bifidobacterium. Major SCFAs remained stable, with increases limited to minor protein-derived SCFAs.

SIGNIFICANCE: The MedKD was associated with high adherence, efficacy, and anthropometric improvements, along with modest effects on the lipid profile. Microbial and SCFA changes reflected both the epilepsy-related milieu and potential influences of the diet's high olive oil content.