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Human Milk Oligosaccharides for Prevention of Alcohol-Associated Liver Disease

母乳低聚糖用于预防酒精相关性肝病

基本信息

批准号：
10266673
负责人：
Derrick E Fouts
金额：
$ 15.78万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-22 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10266673
关键词：
Acute Administrative Supplement Affect Alcohol abuse Alcoholic Hepatitis Alcoholic Liver Diseases Alcohols Bacteriophages Cessation of life Chronic Chronic Disease Cytolysins Data Developed Countries Development Dietary Supplementation Disease Enteral Enterococcus faecalis Epithelial Cells Ethanol Etiology Exotoxins Experimental Models Fucose Galactose Glycocalyx Glycoproteins Goals Health Hepatocyte Human Milk Infant formula Intestinal Mucosa Intestinal permeability Intestines Laboratories Liver Liver diseases Mediating Medical Monitor Morbidity - disease rate Mus Nature Nutrient Oligosaccharides Patients Polysaccharides Pre-Clinical Model Prevention strategy Preventive Publications Publishing Research Role Sampling Secretor blood group alpha-2-fucosyltransferase Severity of illness Steatohepatitis Surface Systems Biology Toxin United States alcohol prevention alcohol use disorder apical membrane bacteriome base chronic alcohol ingestion cost design dietary supplements dysbiosis gut colonization gut dysbiosis gut microbiome gut microbiota humanized mouse improved innovation insight intestinal epithelium liver injury microbiome research microbiota mortality novel pathobiont prevent resistance factors transcriptome

项目摘要

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.

项目总结