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Gut. 2018 May;67(5):891-901. doi: 10.1136/gutjnl-2016-313432. Epub 2017 May 26.

Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease.

Author information

1
Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria.
2
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
3
Department of Inflammation, Chemokines and Immunopathology, INSERM UMR996, Clamart, France.
4
Center for Microbiome Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
5
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
6
Univ Paris-Sud, Univ Paris-Saclay, DHU Hepatinov, Labex Lermit, CHU Bicêtre, Kremlin-Bicêtre, France.
7
AP-HP, Hepatogastroenterology and Nutrition, Hôpital Antoine-Béclère, Clamart, France.
8
Department of Dermatology, University Hospital Zürich, Zürich, Switzerland.
9
Institute of Pathology, Medical University Innsbruck, Innsbruck, Austria.
#
Contributed equally

Abstract

OBJECTIVE:

Alcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. Akkermansia muciniphila, a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of A. muciniphila administration on the course of ALD.

DESIGN:

The intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal A. muciniphila abundance was determined in a cohort of patients with alcoholic steatohepatitis (ASH). The impact of A. muciniphila on the development of experimental acute and chronic ALD was determined in a preventive and therapeutic setting, and intestinal barrier integrity was analysed.

RESULTS:

Patients with ASH exhibited a decreased abundance of faecal A. muciniphila when compared with healthy controls that indirectly correlated with hepatic disease severity. Ethanol feeding of wild-type mice resulted in a prominent decline in A. muciniphila abundance. Ethanol-induced intestinal A. muciniphila depletion could be restored by oral A. muciniphila supplementation. Furthermore, A. muciniphila administration when performed in a preventive setting decreased hepatic injury, steatosis and neutrophil infiltration. A. muciniphila also protected against ethanol-induced gut leakiness, enhanced mucus thickness and tight-junction expression. In already established ALD, A. muciniphila used therapeutically ameliorated hepatic injury and neutrophil infiltration.

CONCLUSION:

Ethanol exposure diminishes intestinal A. muciniphila abundance in both mice and humans and can be recovered in experimental ALD by oral supplementation. A. muciniphila promotes intestinal barrier integrity and ameliorates experimental ALD. Our data suggest that patients with ALD might benefit from A. muciniphila supplementation.

KEYWORDS:

Akkermansia muciniphila ; alcoholic liver disease; alcoholic steatohepatitis; gut barrier; intestinal microbiota

PMID:
28550049
DOI:
10.1136/gutjnl-2016-313432
[Indexed for MEDLINE]

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