To compare the gut microbiome among persons with epilepsy (PWE) with and without  depression.  

Epilepsy and depression are highly comorbid. Thus, many hypothesize that common neurobiological mechanisms underlie both conditions. The gut-brain-axis has been proposed to be involved individually in epileptogenesis and major depressive disorder. The present study bridges these two lines of research by investigating the gut microbiome in comorbid epilepsy and depression.    

Eighty-five PWE with various epilepsy types collected a stool sample after seizure freedom for ≥7 days. Medical records were reviewed for clinical characteristics and documentation of a depression diagnosis, and participants completed depression screeners and a food-frequency-questionnaire. We extracted microbial DNA and performed Shotgun Metagenomic sequencing using an Illumina NextSeq 1000. The KneadData pipeline was used for quality control on paired-end raw sequencing reads (2x150 bp) in FASTQ format. We used the following programs to profile microbial species and metabolic pathways: MetaPhlAn4.2.2 and HUMAnN 3.9.

Individuals with (n=36) and without depression (n=49) did not differ on demographic variables, epilepsy diagnostic variables, including drug-resistance, and diet. A lower proportion of individuals with depression (n=27, 33.33%) were taking Levetiracetam than those without depression (not depressed: n=24, 48.98%; p=.042, φ=.243). Bacterial taxonomic and functional pathway beta-diversity differed between individuals with depression or without (p=.018) but did not differ between those who were and were not taking Levetiracetam (p=.065). Individuals with depression were depleted of the following microbiota: Roseburia faecis (p=.022), Ruminococcin bicirculans (p=.049), and Blautia Obeum (p=.006) and displayed higher levels of the following microbiota: Ruminococcus torques (p=.048), Phocaeicola dorei (p=.041), and Faecalimonas umbilicata (p=.005).

The gut microbiome differs in individuals with comorbid depression and epilepsy from those without depression. Gut dysbiosis may be a potential treatment target for comorbid depression and epilepsy.