# Microbiome as therapeutic target in alcoholic hepatitis

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $301,538

## Abstract

Project Summary
Alcohol associated health problems are a major medical burden in industrialized countries. Alcoholic
hepatitis (AH) is a distinct acute on chronic disease with significant morbidity and mortality. Patients with
alcoholic hepatitis show intestinal dysbiosis and increased intestinal permeability. Recent evidence
suggests that AH is a gut dysbiosis driven disease. The mechanism of how the microbiota contributes to AH
is largely unknown. Results from our laboratories suggest that alterations in the bacterial microbiome
contribute to the development of alcoholic liver disease. We observed significantly greater numbers of
Enterococcus faecalis in fecal samples from AH patients, which exacerbates alcoholic liver disease in
preclinical models. Although the intestinal microbiome consists of bacteria, fungi, bacteriophages and
viruses, research in the field of alcoholic liver disease has almost exclusively focused on the interaction
between the host and bacteria. We demonstrate alcohol-associated compositional changes in gut fungal
populations with reduced fungal diversity and overgrowth of Candida albicans in AH patients. The degree of
exposure to fungal products such as β-glucan correlates with mortality in patients with cirrhosis due to
alcohol abuse. We have generated a testable central hypothesis of this proposed collaborative research
application that implicates disturbances in intestinal bacteria, bacteriophages and fungi as important
etiological factors for the development of AH. We predict that the degree of dysbiosis and translocated
microbial products correlate with levels of systemic and hepatic inflammation, and with AH severity.
Through the proposed study we will characterize gut bacteriophages and bacteria in patients with AH.
Towards this goal, we will use lytic bacteriophages to reduce intestinal Enterococcus faecalis and improve
liver disease in a humanized AH model (Aim 1). We will characterize the intestinal mycobiome in patients
with AH. Reducing intestinal fungal overgrowth with antifungals or supplementation with probiotic
Saccharomyces boulardii will ameliorate liver disease in a humanized AH model (Aim 2). We believe these
studies will provide important insights into the contribution of the intestinal microbiome to AH. Eventually this
approach will lead to new therapeutics for patients with alcoholic hepatitis.

## Key facts

- **NIH application ID:** 10427256
- **Project number:** 5U01AA026939-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Derrick E Fouts
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $301,538
- **Award type:** 5
- **Project period:** 2018-09-22 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427256

## Citation

> US National Institutes of Health, RePORTER application 10427256, Microbiome as therapeutic target in alcoholic hepatitis (5U01AA026939-05). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10427256. Licensed CC0.

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