Abstract Details

Previous studies used 16S-rRNA gene sequencing to study GM among patients with epilepsy (PWE). Whole-genome shotgun metagenomic sequencing allows more comprehensive characterization of taxonomic composition, functional contribution, and relative abundance of gut microbiota.

To study the role of gut microbiome (GM) in epilepsy, and its possible correlation with treatment refractoriness.

Patients aged >18 with focal-onset epilepsy were recruited, including 17 with drug-resistant (DRE) and 20 with drug-sensitive epilepsy (DSE). Stool samples were collected with OMNIgeneGUT devices, followed by DNA extraction and shotgun metagenomic sequencing on Illumina NovaSeq 6000 platform. These were compared against GM metagenomic data from 132 healthy controls.

Significant heterogeneity in relative abundance of GM was noted. At genus level, Phocaeicola and Bacteroidetes were increased in all PWE, while Blautia and Ruminococcus were decreased compared to healthy controls. The Firmicutes/Bacteroidetes ratio, a measure of GM dysbiosis, was significantly lower in both DSE and DRE compared to healthy controls (p<0.01), with no significant difference between DSE and DRE (p=0.36). Alpha diversity indices of gut microbiota were significantly lower in PWE compared to healthy controls (p<0.01) but were not significantly different between DSE and DRE. Pairwise PERMANOVA showed significant difference between PWE and healthy controls in terms of beta diversity.

Lefse analysis revealed that 23 taxonomic units differed significantly between DSE and DRE. Univariate linear regression models further showed that Clostridium sp AT4 and Acidaminococcus intestini (p<0.01) were independently associated with DRE regardless of age and sex-adjustment. 

PWE were associated with gut dysbiosis compared with healthy controls. Significant heterogeneity in relative abundance of GM was noted between DSE and DRE, where Clostridium sp AT4 and Acidaminococcus intestini were independently associated with drug-resistant status. A full-scale metagenomic study with a larger sample size will shed light on the role of gut dysbiosis in epilepsy, and thus potential treatment options in DRE.