Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Microbiology
First Advisor
Goodman, Andrew
Abstract
Medical drugs, especially orally delivered medical drugs, remain one of the most w¬idely used methods for treating diseases and ameliorating disease symptoms. Furthermore, all humans are colonized with a diverse representation of bacteria in their gastrointestinal tracts. As such, medical drugs administered to patients will encounter the gut microbiome. This dissertation describes some possible interactions occurring between host, drug, and the gut microbiome, and how these interactions can affect hos¬¬t health. The first example I present describes the intertwining of Parkinson’s disease (PD) drug-based therapies with the gut microbiome through a complex network of interactions. One group of PD drugs, catechol-O-methyltransferase inhibitors (COMT-I’s) aim to increase the efficacy of the main drug used in PD therapy, levodopa. However, I have uncovered the counterintuitive actions that COMT-I drugs may have on levodopa therapy through altering the gut microbiome via antibiotic-like effects of these host-targeted drugs. In another example, I describe a discovery in which bacterial nitroreduction of the COMT-I tolcapone disrupts its ability to inhibit host COMT enzymes. I also present another set of examples to which I have contributed throughout my tenure. These studies investigate different aspects of the host, the microbiome, xenobiotic compounds, and how these all can contribute to previously unknown effects on host health or microbiome dynamics. Taken together, this thesis further advances our knowledge surrounding the complex interactions between medical drugs, the host, and the gut microbiome.
Recommended Citation
Verdegaal, Andrew Albert, "Impact of Medical Drugs on Microbiome Dynamics" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1289.
https://elischolar.library.yale.edu/gsas_dissertations/1289
