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Author ORCID Identifier
https://orcid.org/0000-0002-1515-1894
Date Available
5-19-2026
Year of Publication
2026
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Pharmacy
Department/School/Program
Pharmaceutical Sciences
Faculty
Ilhem Messaoudi
Faculty
David Feola
Abstract
Alcohol consumption is widespread in the United States, with 80% of individuals aged 12 and older reporting alcohol use and 1-in-4 engaging in risky drinking behaviors. Alcohol misuse heightens susceptibility to infections and delays wound healing, indicating a disrupted immune system. Previous studies show alcohol rewires immune cells, especially monocytes and macrophages, which play critical roles in tissue homeostasis and host defense.
Using a rhesus macaque model of ethanol self-administration, we demonstrate that after 6-months of drinking, monocytes exhibit decreased cytokine production and significant transcriptomic changes, indicating a hypo-inflammatory state. In contrast, 12-months of chronic alcohol use induces hyperinflammatory responses, evidenced by increased secretion of immune mediators and expression of inflammatory genes.
Mechanisms underlying these changes are incompletely understood, but mounting evidence suggests translocation of intestinal bacterial products/metabolites can train monocytes. However, specific microbial and metabolite changes remain undefined. Using fecal samples, we found 6-months of drinking alters the abundance of short-chain fatty acid (SCFA) producers and increases intestinal microbes linked to negative regulation of inflammation. In contrast, chronic alcohol use decreases SCFA-producing bacteria and disrupts fatty- and amino-acid metabolites. These results highlight a duration-dependent effect of alcohol on gut microbes and metabolites, which may influence variations in monocyte profiles.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2026.305
Archival?
Archival
Funding Information
This work was supported by National Institutes of Health R01AA028735 (Messaoudi), U01AA013510 (Grant), and R24AA019431 (Grant). MB is supported by National Institutes of Health 1F31AA031600-01A1.
Recommended Citation
Blanton, Madison B., "The Immune Hangover: Understanding the Influence of Alcohol Use, Abstinence, and Post-Abstinence Drinking on Monocyte Plasticity" (2026). Theses and Dissertations--Pharmacy. 178.
https://uknowledge.uky.edu/pharmacy_etds/178
SuppTable2_2_List_of_differentially_expressed_genes_6moMono.xlsx (67 kB)
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