Abstract found in Wiley Online Library
Objective: We examined whether post-traumatic epilepsy (PTE) is associated with measurable perturbations in gut microbiome.
Methods: Adult Sprague-Dawley rats were subjected to Lateral Fluid Percussion Injury (LFPI). PTE was examined 7 months after LFPI, during a 4-week continuous video-EEG monitoring. 16S ribosomal ribonucleic acid gene sequencing was performed in fecal samples collected before LFPI/sham-LFPI and 1 week, 1 and 7 months thereafter. Longitudinal analyses of alpha diversity, beta diversity, and differential microbial abundance were performed. Short-chain fatty acids (SCFA) were measured in fecal samples collected before LFPI by Liquid Chromatography with Tandem Mass Spectrometry.
Results: Alpha diversity changed over time in both LFPI and sham-LFPI subjects; no association was observed between alpha diversity and LFPI, the severity of post-LFPI neuromotor impairments, and PTE. LFPI produced significant changes in beta diversity and selective changes in microbial abundances associated with the severity of neuromotor impairments. No association between LFPI-dependent microbial perturbations and PTE was detected. PTE was associated with beta diversity irrespective of timepoint vis-à-vis LFPI, including at baseline. Preexistent fecal microbial abundances of four amplicon sequence variants belonging to the Lachnospiraceae family (three enriched and one depleted) predicted the risk of PTE with area under the curve (AUC) of 0.73. Global SCFA content was associated with the increased risk of PTE with AUC of 0.722, and with 2-Methylbutyric (depleted), valeric (depleted), isobutyric (enriched) and isovaleric (enriched) acids being most important factors (AUC of 0.717). When the analyses of baseline microbial and SCFA compositions were combined, AUC to predict PTE increased to 0.78.
Significance: While lateral fluid percussion injury produces no perturbations in the gut microbiome that are associated with PTE, the risk of PTE can be stratified based on preexistent microbial abundances and short-chain fatty acid content.