Early treatment with rifaximin during epileptogenesis reverses gut alterations and reduces seizure duration in a mouse model of acquired epilepsy

• DOI: 10.1016/j.bbi.2024.04.007
• Publication Date: 2024-04-10T06:54:10Z
• Authors: Valentina Kebede; Teresa Ravizza; Silvia Balosso; Rossella Di Sapia; Luca Canali; Sara Soldi; Serena Galletti; Christina Papazla...; Panagiotis A. Karas; Sotirios Vasileiadis; Annalisa Sforzini; Laura Pasetto; Valentina Bonetto; Annamaria Vezzani; Loredana Vesci
• Keywords: Rifaximin; Neuropathology

The gut microbiota is altered in epilepsy and emerging as a potential target for new therapies. We studied the effects of rifaximin, gastrointestinal tract-specific antibiotic, on seizures neuropathology alterations its mouse model temporal lobe (TLE). Epilepsy was induced by intra-amygdala kainate injection causing status epilepticus (SE) C57Bl6 adult male mice. Sham mice were injected with vehicle. Two cohorts SE fed rifaximin-supplemented diet 21 days, starting either at 24 h post-SE (early disease stage) or day 51 (chronic stage). Corresponding groups (one each standard (control) diet. Cortical ECoG recording done stage (24/7) days all to measure number duration spontaneous during rifaximin treatment control Then, epileptic ± respective sham sacrificed brain, feces collected. Biospecimens used for: (i) quantitative histological analysis structural cellular components; (ii) markers inflammation intestinal barrier integrity RTqPCR; (iii) 16S rRNA metagenomics feces. Hippocampal neuronal cell loss assessed killed early phase. Rifaximin administered reduced seizure (p < 0.01) prevented hilar mossy cells hippocampus compared Epileptic showed reduction both villus height height/crypt depth ratio decreased goblet duodenum, well increased macrophage (Iba1)-immunostaining jejunum 0.05), Rifaximin's effect associated reversal changes, except which remained reduced. Seizure negatively correlated 0.05). Rifaximin-treated also tight junctions (occludin ZO-1, p TNF mRNA expression duodenum chronic did not change Chronic an crypt 0.05) affect these changes. At stages, modified α- β-diversity composition mice, phylum, family genus levels, depended disease. During phase, abundance specific taxa positively In conclusion, gut-related reflecting dysfunctional state, occur development TLE model. A short-term phase disease, neuropathology, reversed some strengthening therapeutic gut-based therapies epilepsy.