Non-alcoholic fatty liver and the gut microbiota

Stavros Bashiardes, Hagit Shapiro, Shachar Rozin, Oren Shibolet, Eran Elinav*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background Non-alcoholic fatty liver (NAFLD) is a common, multi-factorial, and poorly understood liver disease whose incidence is globally rising. NAFLD is generally asymptomatic and associated with other manifestations of the metabolic syndrome. Yet, up to 25% of NAFLD patients develop a progressive inflammatory liver disease termed non-alcoholic steatohepatitis (NASH) that may progress towards cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. In recent years, several lines of evidence suggest that the gut microbiome represents a significant environmental factor contributing to NAFLD development and its progression into NASH. Suggested microbiome-associated mechanisms contributing to NAFLD and NASH include dysbiosis-induced deregulation of the gut endothelial barrier function, which facilitates systemic bacterial translocation, and intestinal and hepatic inflammation. Furthermore, increased microbiome-modulated metabolites such as lipopolysaccharides, short chain fatty acids (SCFAs), bile acids, and ethanol, may affect liver pathology through multiple direct and indirect mechanisms. Scope of review Herein, we discuss the associations, mechanisms, and clinical implications of the microbiome's contribution to NAFLD and NASH. Understanding these contributions to the development of fatty liver pathogenesis and its clinical course may serve as a basis for development of therapeutic microbiome-targeting approaches for treatment and prevention of NAFLD and NASH. Major conclusions Intestinal host–microbiome interactions play diverse roles in the pathogenesis and progression of NAFLD and NASH. Elucidation of the mechanisms driving these microbial effects on the pathogenesis of NAFLD and NASH may enable to identify new diagnostic and therapeutic targets of these common metabolic liver diseases. This article is part of a special issue on microbiota.

Original languageEnglish
Pages (from-to)782-794
Number of pages13
JournalMolecular Metabolism
Volume5
Issue number9
DOIs
StatePublished - 1 Sep 2016

Funding

FundersFunder number
Benoziyo Endowment Fund for the Advancement of Science
Crown Endowment Fund for Immunological Research
European Foundation
Gurwin Family Fund for Scientific Research
Achelis Foundation
Leona M. and Harry B. Helmsley Charitable Trust
European Research Council
Minerva Foundation
German-Israeli Foundation for Scientific Research and Development
Israel Science Foundation
Centre National de la Recherche Scientifique
Abisch-Frenkel-Stiftung
Helmholtz Association
Rising Tide Foundation

    Keywords

    • Liver
    • Microbiome
    • NAFLD
    • NASH

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