Topiramate alters the gut microbiome to aid in its anti-seizure effect

Frontiers in Microbiology

Microbiology

K'Ehleyr Thai¹  Michael W. Taylor²  Tatiane Fernandes²  Susan L. Campbell³  Eunice A. Akinade⁴ 

[1] Graduate Program in Translational Biology Medicine and Health, Virginia Tech, Roanoke, VA, United States;School of Animal Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States;School of Animal Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States;School of Animal Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States;School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States;School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States;

关键词: Lactobacillus johnsonii;    anti-epileptic drugs;    anti-seizure medication;    PTZ;    butyrate;    epilepsy;    gut microbiome;    gut microbiota;   

DOI  :  10.3389/fmicb.2023.1242856

 received in 2023-06-19, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThere is a growing interest in the role of the gut microbiota in epilepsy, however, it is unclear if anti-seizure medications (ASMs) play a role in the gut-brain axis. To test this, we investigated the impact of the ASM topiramate on the gut microbiome of mice.MethodsC57BL/6J mice were administered topiramate in their drinking water for 5 weeks. 16S ribosomal RNA gene sequencing was performed on fecal samples collected at 5 weeks. Analysis of alpha diversity, beta diversity, and differential abundance were performed. Cecal contents were analyzed for short-chain fatty acids (SCFAs) composition. Pentylenetetrazol (PTZ)-kindling was performed in saline, topiramate, Lactobacillus johnsonii, and topiramate and Lactobacillus johnsonii treated mice. Mice received PTZ injection every other day for a total of twelve injections, seizure activity was video monitored for 30 minutes and scored.Results and discussionOur study revealed that topiramate ingestion significantly increased Lactobacillus johnsonii in the gut microbiome of naïve mice. Treatment with topiramate and Lactobacillus johnsonii together, but not alone, reduced susceptibility to PTZ-induced seizures. Co-treatment also significantly increased the percent of butyrate and the abundance of butyrate-producing family Lachnospiraceae in the gut, and elevated the GABA/glutamate ratio in the cortex. Our results demonstrate that an ASM can alter the gut microbiome to aid in their anti-seizure effect in vivo and suggest the potential of the probiotic Lactobacillus johnsonii as an adjunct therapy with topiramate in reducing seizure susceptibility.

【 授权许可】

Unknown   
Copyright © 2023 Thai, Taylor, Fernandes, Akinade and Campbell.