# Human Milk Oligosaccharides for Prevention of Alcohol-Associated Liver Disease

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $157,750

## Abstract

Project Summary
Alcohol associated health problems are a major medical burden in industrialized countries. Alcoholic
hepatitis 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 alcohol-associated liver disease is a gut dysbiosis driven disease. The mechanism of how the
microbiota contributes to alcohol-associated liver disease is largely unknown. Results from our laboratory
suggest that alterations in the bacterial microbiome contribute to the development of alcoholic liver disease.
We observed significantly greater numbers of cytolysin-positive Enterococcus faecalis (E. faecalis) in fecal
samples from patients with alcoholic hepatitis, which exacerbates alcoholic liver disease in preclinical
models. How chronic alcohol use results in increased cytolysin-positive E. faecalis in the intestine is not
known. This Administrative Supplement application will use Human Milk Oligosaccharides (HMOs) as
dietary supplement for prevention of alcohol-associated liver disease. We hypothesize that higher
numbers of intestinal E. faecalis in the intestine of patients with alcohol use disorder are facilitated by
alcohol-associated changes in the glycocalyx of intestinal epithelial cells. We predict that changes in the
intestinal glycocalyx can be compensated by dietary supplementation with HMOs. Through the proposed
study we will characterize the role of HMOs as important resistance factor for intestinal E. faecalis
colonization. Towards this goal, we will use different HMOs as dietary supplements to reduce intestinal E.
faecalis and prevent ethanol-induced liver disease in mice (Specific Aim). Our studies will gain novel
insights into the contributions of the intestinal microbiota to alcohol-related liver disease, and will find
innovative prevention strategies for these diseases. HMOs are ideal supplements, they are safe with a
precedent for FDA generally recognized as safe (GRAS) and available from multiple different supplies at
large scale and low costs.

## Key facts

- **NIH application ID:** 10266673
- **Project number:** 3U01AA026939-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Derrick E Fouts
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $157,750
- **Award type:** 3
- **Project period:** 2018-09-22 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10266673

## Citation

> US National Institutes of Health, RePORTER application 10266673, Human Milk Oligosaccharides for Prevention of Alcohol-Associated Liver Disease (3U01AA026939-04S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10266673. Licensed CC0.

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