Defense Date

2019

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Dr. Janina Lewis

Abstract

Opioids are prescribed to millions of people each year, especially to help patients cope with chronic pain, something from which more than a fifth of U.S. adults suffer (CDC). Unfortunately, opioid use and abuse has become a national emergency as the number of opioid prescriptions, opioid misuse, and opioid-related drug overdoses and death have drastically increased in the last twenty years (HHS). Because of the emergent state surrounding opioid use and misuse, the effects of opioids on all aspects of the human body has been an increasingly large focus of research scientists. This study focuses on the possible effect of repeated opioid administration on the gut microbiome.

The human gut microbiome has also been a significant focus for researchers recently as more evidence is unveiling the effects of the gut microbiome on several organs of the body, especially the brain (Galland). It remains unclear the mechanism by which opioids affect humans beyond pain management, particularly cognitive function, mood and behavior. Given the similarities of side effects between gut microbial dysbiosis and chronic opioid use, including decreased gut motility, increased inflammation, altered cognitive function, and behavioral changes, it is possible that some of the effects of opioids on the brain’s cognitive functions are mediated through microbial effectors due to alterations in gut microbial composition upon prolonged usage of opioids. Therefore, our lab took special interest in the possible link between opioids, the gut, and the brain.

It was our aim to provide evidence that repeated Buprenorphine, a partial µ-opioid receptor agonist, dosing alters gut microbial composition. By first isolating DNA from non-human primate fecal samples and analyzing DNA quality we were able to prepare DNA libraries and perform DNA Illumina Next-Generation shotgun sequencing. At the phylum level we observed a fairly common trend in treated subjects of increased Firmicutes during dosing followed by a decrease toward baseline after one week post-dosing. We also observed increases and decreases in the sub-dominant phylum in treated subjects at two weeks of dosing followed by a respective decrease or increase toward baseline after one week post-dosing; however, these trends were less consistent. At the genus level we were unable to observe any trends as a result of opioid administration. Upon performing a non-parametric Wilcoxin Signed-Rank Test, it was determined that there was no significant differential abundance between time points in treated subjects. Quantitative PCR was also performed to validate our sequencing results, but considering the lack of trends we observed, it proved to be difficult to validate anything.

In the end, we were unable to provide significant evidence for our hypothesis. The gut microbiome varies so greatly among and within individuals that finding a significant and consistent alteration in bacterial abundance across all treated subjects proved nearly impossible. What we were able to take away from the study was the observation of some alteration in the microbiome which will need to be studied further by incorporating predicted experimental improvements gleaned from our pilot studies. Despite our results, it is still our hypothesis that opioids affect the microbiome and we encourage future researchers to use our findings as a guide for their experimental design.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-8-2019

Rowe_Anne_MS.pdf (2843 kB)

Available for download on Monday, May 06, 2024

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