Gut microbiome modulation and seizure outcomes following modified Atkins diet in drug-resistant epilepsy

Background and objectives Drug-resistant epilepsy (DRE) affects nearly one-third of individuals with epilepsy. Ketogenic dietary therapies have shown benefit, and emerging evidence suggests a potential role of the gut microbiome in mediating anti-seizure effects. This study evaluated the clinical efficacy of the modified Atkins diet in DRE and explored associated gut microbiome changes. Methods Fifteen patients with DRE were enrolled, of whom 11 adhered to modified Atkins diet for 3 mo. Seizure frequency, ketone levels, and clinical parameters were monitored. Stool samples collected at baseline, 1, and 3 mo underwent 16S rRNA sequencing. Microbiome analyses included alpha diversity, differential abundance, functional prediction using KEGG pathways, and correlation of taxa with seizure frequency. Serum gamma-glutamyl transferase was assessed as a safety marker. Results At 3 mo, 9 of 15 patients (60%) achieved ≥50% reduction in seizure frequency, including 4 with ≥85% reduction. Ketone levels increased significantly over time. Alpha diversity did not differ significantly. Increased relative abundance of Akkermansia and Parabacteroides was observed. Several short-chain fatty acid–producing taxa showed negative correlations with seizure frequency, whereas Subdoligranulum variable demonstrated a positive correlation. Functional predictions suggested enrichment of GABA-related pathways. Interpretations and conclusions Modified Atkins diet was associated with seizure reduction and gut microbial alterations in DRE. These microbiome changes may represent potential correlations of clinical response; however, findings are preliminary and warrant confirmation in larger controlled studies.