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Dissertation Defense: The gut microbiome: A contributing mechanism to the anti-seizure effect of topiramate

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Thai

Dissertation Defense: The gut microbiome: A contributing mechanism to the anti-seizure effect of topiramate

K'Ehleyr Thai

Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Campbell Lab
May 22, 2023 at 10 a.m.,  Room 101, Life Sciences 1

About this Dissertation

Epilepsy is one of the most common neurological disorders worldwide whereby individuals are prone to spontaneous recurrent seizures. As there is no cure for epilepsy, treatment is aimed at providing seizure freedom with antiepileptic drug (AED) treatment. While up to 65% of individuals with epilepsy will have seizures controlled with AEDs, about one third of epilepsy patients are drug resistant, a number that has remained steady despite the over 30 FDA approved AEDs. This represents the most important motivation for researchers to investigate new therapeutic strategies to treat seizures. One new therapeutic strategy that is currently being explored is the gut microbiome. The gut microbiome has received considerable interest in recent years and is implicated in human health and disease, including epilepsy. Growing research demonstrates that alteration of the gut microbiome in human patients with epilepsy and rodent epilepsy models can affect seizure occurrence. Although there are increasing studies investigating the relationship between the gut microbiome and epilepsy, the potential role of AEDs on the gut microbiome in the treatment of seizures has not been studied. This body of work investigates that role.

K'Ehleyr, working in the Campbell lab, demonstrated that the AED topiramate alters the gut microbiome to aid in its anti-seizure effect. The findings from this dissertation are the first to show that AEDs may alter the gut microbiome to aid in their anti-seizure effect, and highlights the potential for probiotics as an adjuvant therapy in seizure management.

More About the Candidate and Project

Education

Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate

Virginia Tech, B.S., Neuroscience, B.S. Psychology

Training

Graduate Research Assistant, Campbell Lab

 

Mentor

Susan Campbell, Assitant Professor, Department of Animal and Poultry Sciences

Committee Members

  • Timothy Jarome, Assistant Professor, Department of Animal and Poultry Science
  • Liwu Li, Professor, Department of Biological Sciences
  • Xin Luo, Associate Professor, Department of Biomedical Sciences and Pathobiology
  • Michelle Olsen, Professor, School of Neuroscience
  • Most Creative Pitch: Commercialization of a Scientific Patent (2017)

Peer-reviewed publications

 Thai, K., Taylor, M. W., Fernandes, T., Akinade, E. A., & Campbell, S. L. Topiramate alters the gut microbiome to aid in its anti-seizure effect. In preparation for submission to Epilepsia.

Kaiser, N., Guo, X., Thai, K., & Campbell, S. L. Infection-induced epilepsy and the gut microbiome. In preparation for submission.

Gallucci, A., Patel, D. C., Thai, K., Trinh, J., Gude, R., Shukla, D., & Campbell, S. L. (2021). Gut metabolite S-equol ameliorates hyperexcitability in entorhinal cortex neurons following Theiler murine encephalomyelitis virus-induced acute seizures. Epilepsia, 62(8), 1829–1841. https://doi.org/10.1111/epi.16979 

Presentations

Thai, K., Taylor, M. W., Fernandes, T., Akinade, E. A., & Campbell, S. L. Topiramate alters the gut microbiome to aid in its anti-seizure effect. (May 2023). Oral presentation at the annual School of Animal Sciences Research Day. Blacksburg, VA.

Thai, K., Taylor, M. W., Akinade, E. A., & Campbell, S. L. (October 2022). The antiepileptic drug topiramate increases Lactobacillus johnsonii which aids in reducing pentylenetetrazol-induced seizures. Poster presented at the CSHL Microbiome 2022 Meeting, Cold Spring Harbor, NY.

Thai, K., Orsi, S. A., Thompson, E., Nyitray, A., Jarome, T.J., & Campbell, S.L. (August 2019). Pediatric glioma have decreased BDNF expression and increased histone methylation at the BDNF promoter. Poster presented at the annual Advancing Neuroscience Research at Virginia Tech, Summer Symposium, Blacksburg, VA.

  • Graduate Student Assembly Delegate, TBMH Delegate (2018-2019)
  • Virginia Tech Campus Development Committee, GSA Delegate (2018-2019)