Abstracts

Rationale: There is growing evidence for the role that the gut-brain axis may play in epileptogenesis and drug resistance in epilepsy. While studies have demonstrated differences in gut microbiome biodiversity between people with epilepsy and healthy controls, no known study has explored gut microbiota as a monitoring biomarker (Russo, 2022). The present report is a preliminary analysis of an ongoing study investigating differences in gut microbiota pre and post focal-impaired awareness (FIA) and tonic-clonic convulsions (TCC).

Methods: Participants were adult patients diagnosed with epilepsy presenting to the epilepsy monitoring unit (EMU) for seizure provocation (N = 18). Exclusion criteria included recent antibiotic use (< 30 days), ketogenic diet, BMI ≥40, and IBD diagnosis. Participants were asked to collect a stool sample using the OMNIgene-GUT kit >7 days after their last seizure (pre-ictal/baseline sample), then four to twenty four hours and two to seven days after experiencing a seizure at the EMU. Microbial DNA was extracted from the stool samples and Shotgun Metagenomic sequencing was performed using Illumina NextSeq 1000. Paired end raw sequencing reads (2x150 bp) in FASTQ format were quality controlled using KneadData pipeline. Processed metagenomic reads were then classified using Kraken2 pipeline for microbial community taxonomic profiling. HUMAnN 3.0 pipeline was used to profile the abundance of UniRef90 gene families and microbial metabolic pathways in the samples.

Results: There were no significant differences observed in the overall beta diversity in the gut microbiome before and after a seizure (PERMANOVA, p = 0.9) and between FIAs and TCCs (PERMANOVA, p = 0.2). However, differential abundance analysis (Wilcoxon rank sum test, p < 0.05) indicated that there were significant differences in the taxa relative abundance. Following a seizure, there was an overrepresentation of Catenibacterium, Faecalicatena, Flintibacter, Amedibacterium, and Solibaculum genera. Additionally, postictal gut microbial composition differed according to seizure type: Anaerostipes and Olsenella were overrepresented among those experiencing TCCs, while Desulfovibrio, Prevotella, Butyrycimonas, Leuconostoc, Simiaoa, and Weissella were underrepresented after TCCs compared to FIAs. Analysis of the functional pathways (Wilcoxon rank sum test, p < 0.05) in the gut microbiota demonstrated a postictal depletion of gut microbes associated with biosynthesis of certain fatty acids (palmitate, stearate, palmitoleate) and sugars (rhamnose), as well as the Entner-Doudoroff and formaldehyde oxidation pathways.