Date of Award

Spring 4-18-2024

Embargo Period

5-18-2025

Document Type

Dissertation - MUSC Only

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

College

College of Graduate Studies

First Advisor

Lindsay Squeglia

Second Advisor

Mindy Engevik

Third Advisor

Jens Jensen

Fourth Advisor

Jennifer Rinker

Fifth Advisor

Lawrence Chandler

Abstract

Early alcohol use is an important risk factor for alcohol and substance use disorders, but the neurobiological changes that lead to increased vulnerability are not well understood. Alcohol-induced alterations in the microbiome at an early age may lead to neural changes that affect the escalation of alcohol use. Consequently, the microbiome is a novel area of research for adolescent alcohol use disorder (AUD). The present studies investigated differences in the oral microbiome of human adolescents (ages 17-19) who engage in heavy drinking (n=21, 52.4% female) compared to non-drinking control participants (n=18, 44.4% female). We explored associations between the oral microbiome, oral cytokine mRNA levels (interleukin 6 [IL-6], interleukin 1 beta [IL-1β], tumor necrosis factor alpha [TNF-α]), and proton magnetic resonance spectroscopy markers of neuroinflammation (myo-inositol, total choline, total creatine, N-Acetylaspartate). As hypothesized, adolescents who engaged in heavy drinking had significant differences in the diversity and composition of the oral microbiome. Compared to the control group, the alcohol-using group exhibited lower evenness and higher abundances of Rothia and Corynebacterium. We observed no significant differences in cytokine mRNA levels between the groups; however, levels of IL-1β correlated with the abundances of several genera in both groups, including abundances of Rothia. IL-1β was also associated with a higher number of alcohol use days in the past 90 days and phosphatidylethanol concentrations in the alcohol-using group. While there were no significant group differences in neuroinflammation markers, abundances of Rothia were associated with significantly higher concentrations of total creatine-containing metabolites across the whole sample. The associations between Rothia, mRNA cytokine levels, and neurometabolite levels are intriguing, as Rothia is well known for its high capacity to covert alcohol into acetaldehyde, suggesting a potential link between the oral microbiome and neurobiological processes related to alcohol use. Taken together, these studies indicate that the oral microbiome may be affected by alcohol use and is associated with cytokine mRNA levels and neurometabolite concentrations in individuals who use alcohol and controls. The microbiome may aid in prevention and intervention efforts for adolescent AUD by providing new targets for treatment and/or diagnostic and therapeutic response biomarkers.

Rights

Copyright is held by the author. All rights reserved.

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