# Role of gut microbial ethanol production in alcohol use disorder and alcohol-associated liver disease

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $175,691

## Abstract

PROJECT SUMMARY/ABSTRACT
Excessive alcohol use and alcohol-associated liver disease are two of the leading causes of morbidity and
mortality worldwide. The gut microbiome can modify an individual’s risk for progression of alcohol-associated
liver disease via microbe-derived metabolites such as ethanol. Patients with Autobrewery Syndrome (ABS), a
condition where dysregulated gut microbiota produce high levels of ethanol that is then absorbed into the
bloodstream leading to symptoms of intoxication, are a unique and ideal population for studying the host effects
of gut microbial ethanol production. My preliminary data confirms that gut microbiota from ABS patients produce
more ethanol in culture than that of their controls. Because chronic alcohol consumption can increase gut
permeability, which is associated with persistent psychological symptoms of alcohol withdrawal and increased
bacterial translocation to the liver resulting in liver disease progression, we hypothesized that endogenous gut
microbial ethanol production could cause similar effects. Indeed, my additional preliminary data demonstrates
that gnotobiotic mice humanized with high ethanol-producing gut microbiota from ABS patients demonstrated
increased voluntary alcohol use behavior compared with control-humanized mice and increased hepatic
inflammatory gene expression. I then confirmed that the gut microbiota of a subset of patients with alcohol use
disorder also produce significant amounts of ethanol in culture. These observations have led to my central
hypothesis that pathologic gut microbial ethanol production is an independent risk factor for increased alcohol
consumption and exacerbation of liver disease. Hence, the aims of this application are to 1) characterize the
gut microbiota of patients with ABS and identify microbes responsible for high levels of ethanol production, 2)
examine how pathologic gut microbial ethanol production affects host alcohol use and liver disease progression
and test antimicrobials as a therapeutic strategy, and 3) establish gut-microbial ethanol production as an
independent risk factor for a subset of patients with alcohol use disorder and alcohol-associated liver disease.
My proposed studies will advance our understanding of the biological mechanisms that drive ABS and
predisposition for increased alcohol use and liver disease progression, and test potential therapies. The
proposed research and career development plan, along with my mentors, advisory committee, and resources at
the University of California, San Diego, will provide the support and additional training necessary for me to
become an independent physician scientist studying the gut-liver-brain axis in an academic research
environment.

## Key facts

- **NIH application ID:** 10931622
- **Project number:** 5K99AA031328-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Cynthia Li-Shin Hsu
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $175,691
- **Award type:** 5
- **Project period:** 2023-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931622

## Citation

> US National Institutes of Health, RePORTER application 10931622, Role of gut microbial ethanol production in alcohol use disorder and alcohol-associated liver disease (5K99AA031328-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10931622. Licensed CC0.

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