Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: an input for novel therapies.

Abstract

Non-alcoholic fatty liver disease is a multifactorial condition, ranging from simple steatosis to non-alcoholic steatohepatitis with or without fibrosis. In non-alcoholic fatty liver disease, alteration of gut microbiota and increased intestinal permeability increase exposure of the liver to gut-derived bacterial products: lipopolysaccharides and unmethylated CpG DNA. These products stimulate innate immune receptors, namely Toll-like receptors, which activate signalling pathways involved in liver inflammation and fibrogenesis. Currently, there are several studies on the involvement of lipopolysaccharide-activated Toll-like receptor 4 signalling in non-alcoholic fatty liver disease pathogenesis. There has been widespread interest in the study of the involvement of resident hepatic stellate cells and Kupffer cells activation in liver fibrogenesis upon TLR4 stimulation. Although the best evidence to support a role for gut microbiota in non-alcoholic fatty liver disease-induced fibrosis comes largely from animal models, data from human studies are accumulating and could lead to new therapeutic approaches. Therapeutic modulation of gut microflora may be an alternative strategy to develop an anti-fibrotic therapy. In this review, we discuss the relevant role of gut-liver axis in non-alcoholic liver disease-associated liver fibrosis and discuss the evidence on novel anti-fibrotic therapeutic approaches.

• Authors: Otilia E Frasinariu, Sara Ceccarelli, Anna Alisi, Evelina Moraru, Valerio Nobili
• Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (Dig Liver Dis) Vol. 45 Issue 7 Pg. 543-51 (Jul 2013) ISSN: 1878-3562 [Electronic] Netherlands
• PMID: 23280158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chemical References

• DNA, Bacterial
• Lipopolysaccharides
• Toll-Like Receptor 4

Topics

• Animals
• CpG Islands (immunology)
• DNA, Bacterial (immunology)
• Fatty Liver (immunology, metabolism, therapy)
• Humans
• Immunity, Innate
• Intestinal Absorption
• Intestinal Mucosa (immunology, microbiology)
• Lipopolysaccharides (immunology)
• Liver Cirrhosis (immunology, metabolism, therapy)
• Microbiota (immunology)
• Non-alcoholic Fatty Liver Disease
• Permeability
• Toll-Like Receptor 4 (immunology)