Deficiency of Intestinal α1-2-Fucosylation Exacerbates Ethanol-Induced Liver Disease in Mice.

Alcoholism / genetics Animals Central Nervous System Depressants / toxicity Disease Models, Animal Dysbiosis / genetics Ethanol / toxicity Fucosyltransferases / genetics Gastrointestinal Microbiome / drug effects Glycocalyx / drug effects Intestinal Mucosa / drug effects Liver / drug effects Liver Diseases, Alcoholic / genetics Mice Galactoside 2-alpha-L-fucosyltransferase
Alcoholic Liver Disease Cytolysin Fucosyltransferase 2 Microbiome Microbiota

Journal

Alcoholism, clinical and experimental research
ISSN: 1530-0277
Titre abrégé: Alcohol Clin Exp Res
Pays: England
ID NLM: 7707242

Informations de publication

Date de publication:
09 2020
Historique:
received: 10 05 2020
revised: 09 06 2020
accepted: 19 06 2020
pubmed: 7 7 2020
medline: 8 10 2021
entrez: 7 7 2020
Statut: ppublish

Résumé

Fucosyltransferase 2 (Fut2)-mediated intestinal α1-2-fucosylation is important in maintaining a symbiotic host-microbiota relationship and can protect against several pathogens. Intestinal dysbiosis is an important factor for the progression of experimental ethanol (EtOH)-induced liver disease, but the role of Fut2 in modulating the intestinal glycocalyx during alcohol-associated liver disease is unknown. We investigated the role of Fut2-mediated intestinal α1-2-fucosylation for the development of alcohol-associated liver disease. Immunohistochemistry staining was applied to evaluate α1-2-fucosylation in duodenal biopsies from patients with alcohol use disorder. Wild-type (WT) and Fut2-deficient littermate mice were subjected to Lieber-DeCarli models of chronic EtOH administration and the chronic-binge EtOH diet (NIAAA model). Intestinal α1-2-fucosylation was down-regulated in patients with alcohol use disorder. Lack of α1-2-fucosylation in Fut2-deficient mice exacerbates chronic EtOH-induced liver injury, steatosis, and inflammation without affecting EtOH metabolism. Dietary supplementation of the α1-2-fucosylated glycan 2'-fucosyllactose (2'-FL) ameliorates EtOH-induced liver disease in Fut2-deficient mice in the NIAAA model. Despite no direct effects on growth of Enterococcus faecalis in vitro, intestinal α1-2-fucosylation reduces colonization of cytolysin-positive E. faecalis in the intestine of EtOH-fed mice. Intestinal α1-2-fucosylation acts as a host-protective mechanism against EtOH-induced liver disease. 2'-FL is an oligosaccharide naturally present in human milk that could be considered as therapeutic agent for alcohol-associated liver disease.

Sections du résumé

BACKGROUND
Fucosyltransferase 2 (Fut2)-mediated intestinal α1-2-fucosylation is important in maintaining a symbiotic host-microbiota relationship and can protect against several pathogens. Intestinal dysbiosis is an important factor for the progression of experimental ethanol (EtOH)-induced liver disease, but the role of Fut2 in modulating the intestinal glycocalyx during alcohol-associated liver disease is unknown. We investigated the role of Fut2-mediated intestinal α1-2-fucosylation for the development of alcohol-associated liver disease.
METHODS
Immunohistochemistry staining was applied to evaluate α1-2-fucosylation in duodenal biopsies from patients with alcohol use disorder. Wild-type (WT) and Fut2-deficient littermate mice were subjected to Lieber-DeCarli models of chronic EtOH administration and the chronic-binge EtOH diet (NIAAA model).
RESULTS
Intestinal α1-2-fucosylation was down-regulated in patients with alcohol use disorder. Lack of α1-2-fucosylation in Fut2-deficient mice exacerbates chronic EtOH-induced liver injury, steatosis, and inflammation without affecting EtOH metabolism. Dietary supplementation of the α1-2-fucosylated glycan 2'-fucosyllactose (2'-FL) ameliorates EtOH-induced liver disease in Fut2-deficient mice in the NIAAA model. Despite no direct effects on growth of Enterococcus faecalis in vitro, intestinal α1-2-fucosylation reduces colonization of cytolysin-positive E. faecalis in the intestine of EtOH-fed mice.
CONCLUSIONS
Intestinal α1-2-fucosylation acts as a host-protective mechanism against EtOH-induced liver disease. 2'-FL is an oligosaccharide naturally present in human milk that could be considered as therapeutic agent for alcohol-associated liver disease.

Identifiants

DOI: 10.1111/acer.14405 PMID: 32628772 PMC: PMC7808344
pubmed: 32628772
doi: 10.1111/acer.14405
pmc: PMC7808344
mid: NIHMS1621304
doi:

Substances chimiques

Central Nervous System Depressants 0
Ethanol 3K9958V90M
Fucosyltransferases EC 2.4.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1842-1851

Subventions

Organisme : NIAAA NIH HHS
ID : R01 AA020703
Pays : United States
Organisme : BLRD VA
ID : I01 BX004594
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK120515
Pays : United States
Organisme : NIAAA NIH HHS
ID : R37 AA020703
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA011999
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA020864
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA026939
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA024726
Pays : United States
Organisme : Biomedical Laboratory Research & Development Service of the VA Office of Research and Development
ID : BX004594
Pays : International

Informations de copyright

© 2020 by the Research Society on Alcoholism. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

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Auteurs

Rongrong Zhou (R)

From the Department of Infectious Diseases, Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China.
Department of Medicine, University of California San Diego, La Jolla, California, USA.

Cristina Llorente (C)

Department of Medicine, University of California San Diego, La Jolla, California, USA.

Jinling Cao (J)

Department of Medicine, University of California San Diego, La Jolla, California, USA.
College of Food Science and Engineering, Shanxi Agricultural University, Taigu, China.

Bei Gao (B)

Department of Medicine, University of California San Diego, La Jolla, California, USA.

Yi Duan (Y)

Department of Medicine, University of California San Diego, La Jolla, California, USA.

Lu Jiang (L)

Department of Medicine, University of California San Diego, La Jolla, California, USA.

Yanhan Wang (Y)

Department of Medicine, University of California San Diego, La Jolla, California, USA.

Vipin Kumar (V)

Department of Medicine, University of California San Diego, La Jolla, California, USA.
ORCID: 0000-0002-2838-2472

Peter Stärkel (P)

St Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium.

Lars Bode (L)

Department of Pediatrics and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), University of California San Diego, La Jolla, California, USA.

Xuegong Fan (X)

From the Department of Infectious Diseases, Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China.

Bernd Schnabl (B)

Department of Medicine, University of California San Diego, La Jolla, California, USA.
Department of Medicine, VA San Diego Healthcare System, San Diego, California, USA.
ORCID: 0000-0002-6281-825X

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Classifications MeSH

questionsmedicales.fr › Troubles mentaux › Troubles liés à une substance › Troubles liés à l'alcool › Alcoolisme › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Eucaryotes › Animaux › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Dépresseurs du système nerveux central › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Dysbiose › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Composés chimiques organiques › Alcools › Éthanol › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Glycosyltransferase › Hexosyltransferases › Fucosyltransferases › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Environnement et santé publique › Environnement › Écosystème › Biodiversité › Biote › Microbiote › Microbiome gastro-intestinal › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Glycocalyx › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Tissus › Membranes › Muqueuse › Muqueuse intestinale › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Système digestif › Foie › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Troubles dus à des produits chimiques › Troubles dus à l'abus d'alcool › Maladies alcooliques du foie › Deficiency of Intestinal α1-2-Fucosylation...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Deficiency of Intestinal α1-2-Fucosylation...