Authors :
Presenting Author: Susan Campbell, Phd – University of Alabama at Birmingham
Eunice Akinade, BS – School of Neuroscience – Virginia Tech; Michael Taylor, BS – School of Animal Science – Virginia Tech; K'Ehleyr Thai, PhD – Translational Biology, Medicine, and Health – Virginia Tech
Rationale:
As one of the most common neurological conditions world-wide, epilepsy imposes a significant burden on patients with consequences regarding quality of life, morbidity and premature mortality. Since only two-thirds of patients respond to anti-seizure medications (ASMs), 33% of patients are deemed drug-resistant, requiring alternative therapies. Ongoing research suggests a role of the gut microbiota in epilepsy. Studies have shown that epilepsy patients have altered gut microbiomes compared to healthy controls, and evidence suggests that gut microbiota alteration affects seizure susceptibility. However, it is unknown whether ASMs which are used to treat seizures, alter the gut microbiota to impact seizure outcomes.
Methods:
We sought to determine if the ASM, topiramate, alters the gut microbiota. C57BL/6J mice were administered a therapeutic dose of topiramate (80 mg/kg) in their drinking water for four weeks, ad libitum. Fresh stool pellets were collected at four weeks post topiramate treatment. A 16S rRNA based microbiome analysis was performed to identify differential abundance in bacteria in topiramate-treated mice compared to controls.
Results:
At the genus level, Lactobacillus was increased in the gut microbiome of topiramate-treated mice and Lactobacillus johnsonii was increased at the species level. To determine the impact of Lactobacillus johnsonii on seizure susceptibility, mice were orally gavage with Lactobacillus johnsonii with and without topiramate. Only the combination of topiramate and Lactobacillus johnsonii led to a reduction in pentylenetetrazol-induced seizures. In addition, there was also a significant increase in the GABA/glutamate ratio in the cortex of mice co-treated with Lactobacillus johnsonii and topiramate.
Conclusions:
These results pinpoint topiramate-induced changes at the species-level that contributes to seizure reduction; highlighting a potential role for the probiotic Lactobacillus johnsonii as an adjuvant therapy by potentiating the antiseizure effect of topiramate.
Funding:
NIH NINDS R01NS128421