# The role of Enterococcus faecalis in alcoholic liver disease

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2020 · —

## Abstract

Alcohol abuse and alcohol-related diseases are a major cause of morbidity and mortality among Veterans.
Chronic alcoholism is associated with changes in the intestinal microbiota, increased intestinal permeability,
and elevated systemic levels of bacterial products. How chronic alcohol use results in intestinal dysbiosis and
whether specific bacterial species mediate alcoholic liver disease is not known. Results from our laboratory
indicate that Enterococcus faecalis (E faecalis) is sufficient to cause mild steatotic liver disease and to
exacerbate alcoholic liver disease in mice. Most importantly, we observed significantly greater numbers of E
faecalis in fecal samples from alcohol-dependent patients with or without liver disease than healthy controls.
Our preliminary data further shows that alcohol-mediated suppression of the antimicrobial protein regenerating
islet derived-3 (REG3G) allows E faecalis colonization of intestinal mucosal surfaces and translocation to the
liver. E faecalis induces liver inflammation via binding to pathogen recognition receptors on Kupffer cells. A
subsequent increase in expression and secretion of the inflammatory cytokine interleukin (IL)-1β contributes to
the development of ethanol-induced liver disease. This is supported by our findings that chimeric mice lacking
toll-like receptor (TLR)-2 on bone-marrow derived cells have reduced E faecalis-exacerbated alcoholic liver
disease. The focus of this application is to characterize the role of E faecalis in preclinical models of alcoholic
liver disease and Veterans with alcohol abuse. We hypothesize that E faecalis is an important etiological factor
in the modulation of hepatic inflammation and the development of alcoholic liver disease. Our experimental
approach is to use mouse models of chronic alcohol feeding to investigate the role of alcohol-induced
suppression of intestinal REG3G. Lower intestinal REG3G facilitates overgrowth of E faecalis on mucosal
surfaces in the intestine and translocation to the liver (Aim 1). We will investigate the molecular mechanism of
how translocation of E faecalis contributes to hepatic inflammation and hepatocyte death during alcoholic liver
disease (Aim 2). Using a precision-microbiome approach, we will test the hypothesis that targeted manipulation
of alcohol-associated dysbiosis can ameliorate alcoholic liver disease (Aim 3). We believe these studies will
provide novel insights into the contribution of the microbiota to alcoholic liver disease. Innovative and novel
strategies will be developed to prevent or ameliorate alcoholic liver disease in Veterans.

## Key facts

- **NIH application ID:** 9842266
- **Project number:** 5I01BX004594-02
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Bernd G. Schnabl
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842266

## Citation

> US National Institutes of Health, RePORTER application 9842266, The role of Enterococcus faecalis in alcoholic liver disease (5I01BX004594-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842266. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*