# The Role of the Intestinal Mycobiome in Alcoholic Liver Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $327,904

## Abstract

Project Summary
Alcohol associated health problems are a major medical burden in industrialized countries. Patients with
alcoholic liver disease show intestinal bacterial dysbiosis and increased intestinal permeability. Disease
severity correlates with systemic levels of translocated bacterial products. Although there is considerable
progress in understanding the interaction between the host and intestinal bacteria, the role of the intestinal
fungal microbiome (also called mycobiome) in alcoholic liver disease has not been investigated. Results
from an international collaboration by Schnabl, Stärkel and Fouts laboratories suggest that quantitative
changes in the intestinal mycobiome and translocation of fungal products occur in a mouse model of
alcoholic liver disease, while deep sequencing demonstrates intestinal fungal dysbiosis in patients with
chronic alcohol abuse. Reducing intestinal fungal overgrowth with antifungals or restoring intestinal barrier
function using probiotic Saccharomyces boulardii ameliorates experimental alcoholic liver disease. The
central hypothesis of this proposed collaborative research application implicates disturbances in the
intestinal mycobiome as an important etiological factor in the modulation of hepatic and systemic
inflammation, and the development of alcoholic liver disease. We predict that chronic alcohol suppresses
the intestinal immune system and facilitates qualitative and quantitative changes in the intestinal
mycobiome. Fungal products such as β-glucan translocate to the portal circulation and liver, and cause
progression of alcoholic liver disease. Towards this goal, we will use pharmacological interventions,
supplementation of probiotics and genetically modified mice in preclinical mouse models of alcoholic liver
disease (Aim 1). We will characterize the intestinal mycobiome in patients with alcohol abuse, mild and
progressive alcoholic liver disease. We predict that translocated fungal products correlate with levels of
systemic and hepatic inflammation, and with the degree of liver disease (Aim 2). We believe these studies
will provide important insights into alcohol-mediated changes of the intestinal mycobiome that result in
fungal translocation. Eventually this approach might lead to new therapeutic targets for patients with
alcoholic liver disease.

## Key facts

- **NIH application ID:** 10130423
- **Project number:** 5R01AA024726-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Bernd G. Schnabl
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $327,904
- **Award type:** 5
- **Project period:** 2017-04-10 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130423

## Citation

> US National Institutes of Health, RePORTER application 10130423, The Role of the Intestinal Mycobiome in Alcoholic Liver Disease (5R01AA024726-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130423. Licensed CC0.

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