# The role of the gut microbiome as a non-genetic factor in influencing excessive alcohol drinking.

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $201,523

## Abstract

Alcohol Use Disorder (AUD) is a devastating disease with negative health, social, and economic
consequences. AUD susceptibility is regulated by both genetic and non-genetic factors. While
advances in genetics and genomics have allowed us to gain insight into the role of host genes in
AUD, environmental contributions to AUD such as the microbiome, have not been well defined.
The gut microbiome represents a non-genetic contributor to many neuro-psychological conditions.
Although several studies have established that acute and chronic alcohol use is associated with
dysbiosis of the gut microbiome, no study has investigated whether the basal gut microbiome
(before drinking) influences the risk of developing excessive drinking. Work by us and others
showed that genetically identical C57BL/6J (B6J) mice varied widely in alcohol intake and blood
ethanol concentration (BEC). Our microbiome and metabolite analysis showed mice with lower
levels of butyrate in stool, prior to alcohol intake, had higher levels of alcohol intake and BEC, and
harbored a lower level of Clostridia bacteria, compared to low-drinking mice. Butyrate is a group
of short-chain fatty acids (SCFAs) produced by gut microbes through fermentation. Clostridia
possess strong immune-modulatory properties and are a major producer of butyrate. Butyrate
can function as histone deacetylase inhibitors (HDACi), which affect gene expression by histone
modification. Epigenetic regulation of gene expression has emerged as a potentially important
mechanism in the regulation of alcohol intake. We hypothesize that the gut microbiome /microbial
metabolites can regulate chromatin plasticity in brain, and subsequently altering neuronal
transcription and eventually affecting behavior. In Aim 1, we will establish correlations between
the gut microbiome/metabolites, alcohol drinking, and epigenetic alterations of B6J mice. This aim
will confirm our preliminary findings with a large sample size and extend to epigenetic
characterization of mice with differential drinking. In Aim 2, we will test whether high- and low-
drinking phenotypes are transmissible using fecal transplantation, and further test whether
specific microbes and/or metabolites are responsible for differential drinking behavior. Epigenetic
characterization including histone modification and global gene expression will be performed to
gain mechanistic insight into the influence of the microbiome on alcohol preference. Our proposed
work will test the role of the gut microbiome in alcohol preference, improve our understanding of
the etiology of AUD, and lay the groundwork to develop novel therapeutic strategies for AUD,
including pro- and/or prebiotic manipulation of the gut microbiome.

## Key facts

- **NIH application ID:** 10166734
- **Project number:** 5R21AA027858-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Yanjiao Zhou
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $201,523
- **Award type:** 5
- **Project period:** 2020-05-20 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166734

## Citation

> US National Institutes of Health, RePORTER application 10166734, The role of the gut microbiome as a non-genetic factor in influencing excessive alcohol drinking. (5R21AA027858-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166734. Licensed CC0.

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