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

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    Authors
    Lowe, Patrick
    Gyongyosi, Benedek
    Ward, Doyle V.
    Szabo, Gyongyi
    UMass Chan Affiliations
    UMass Metabolic Network
    Department of Microbiology and Physiological Systems
    Center for Microbiome Research
    Department of Medicine, Division of Gastroenterology
    Document Type
    Journal Article
    Publication Date
    2017-05-26
    Keywords
    Akkermansia muciniphila
    alcoholic liver disease
    alcoholic steatohepatitis
    gut barrier
    intestinal microbiota
    Biochemistry
    Cell Biology
    Cellular and Molecular Physiology
    Gastroenterology
    Molecular Biology
    
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    Link to Full Text
    https://doi.org/10.1136/gutjnl-2016-313432
    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.
    Source
    Gut. 2017 May 26. pii: gutjnl-2016-313432. doi: 10.1136/gutjnl-2016-313432. Link to article on publisher's site
    DOI
    10.1136/gutjnl-2016-313432
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/36591
    PubMed ID
    28550049
    Notes

    Full author list omitted for brevity. For the full list of authors, see article.

    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1136/gutjnl-2016-313432
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