title: 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.affiliation: Discipline of Pediatrics, Department of Mother and Child Medicine, University of Medicine and Pharmacy, Grigore T. Popa, Iasi, Iasi, Romania.
authors.forename: Otilia E
authors.initials: OE
authors.lastname: Frasinariu
authors.forename: Sara
authors.initials: S
authors.lastname: Ceccarelli
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
authors.forename: Evelina
authors.initials: E
authors.lastname: Moraru
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
mesh_terms: D000818:Animals; D018899:CpG Islands / Q000276:immunology; D004269:DNA, Bacterial / Q000276:immunology; D005234:Fatty Liver / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007113:Immunity, Innate; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D064307:Microbiota / Q000276:immunology*; D065626:Non-alcoholic Fatty Liver Disease; D010539:Permeability; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D004269:DNA, Bacterial; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4