Medication‐resistant epilepsy is associated with a unique gut microbiota signature

Abstract

Abstract Objective Dysfunction of the microbiota–gut–brain axis is emerging as a new pathogenic mechanism in epilepsy, potentially impacting on medication response and disease outcome. We investigated the composition of the gut microbiota in a cohort of medication‐resistant (MR) and medication‐sensitive (MS) pediatric patients with epilepsy. Methods Children with epilepsy of genetic and presumed genetic etiologies were evaluated clinically and subgrouped into MR and MS. Age‐matched healthy controls (HCs) were also recruited. A food diary was used to evaluate nutritional habits, and the Rome IV questionnaire was used to record gastrointestinal symptoms. The microbiota composition was assessed in stool samples through 16S rRNA. α‐Diversity (AD) and β‐diversity (BD) were calculated, and differential abundance analysis was performed using linear multivariable models (significance: p .adj < .05). Results Forty‐one patients (MR:MS = 20:21) with a mean age of 7.2 years (±4.6 SD) and 27 age‐matched HCs were recruited. No significant differences in AD were found when comparing patients and HCs. Significant positive correlation was found between AD and age (Chao1 p .adj = .0004, Shannon p .adj = .0004, Simpson p .adj = .0028). BD depicted a different bacterial profile in the epilepsy groups compared to HCs (MS vs. HC: Bray–Curtis F = 1.783, p = .001; Jaccard F = 1.24, p = .001; MR vs. HC: Bray–Curtis F = 2.24, p = .001; Jaccard F = 1.364, p = .001). At the genus level, the epilepsy groups were characterized by a significant increase in Hungatella (MS vs. HC: +4.95 log 2 change; MR vs. HC: +6.72 log 2 change); the [Eubacterium] siraeum group changed between the MR and MS subgroups. Significance Epileptic patients display unique gut metagenomic signatures compared to HCs. Moreover, a different ratio of the butyrate‐producing [Eubacterium] siraeum group suggests dissimilarities between patients based on the response to antiseizure medications.