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2016 ; 5
(9
): 782-94
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Non-alcoholic fatty liver and the gut microbiota
#MMPMID27617201
Bashiardes S
; Shapiro H
; Rozin S
; Shibolet O
; Elinav E
Mol Metab
2016[Sep]; 5
(9
): 782-94
PMID27617201
show ga
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.
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