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World J Gastroenterol. Nov 28, 2014; 20(44): 16639-16648
Published online Nov 28, 2014. doi: 10.3748/wjg.v20.i44.16639
Gut microbiota in alcoholic liver disease: Pathogenetic role and therapeutic perspectives
Giulia Malaguarnera, Maria Giordano, Giuseppe Nunnari, Gaetano Bertino, Michele Malaguarnera
Giulia Malaguarnera, Michele Malaguarnera, Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, 95100 Catania, Italy
Maria Giordano, Research Centre “The Great Senescence”, University of Catania, Cannizzaro Hospital, 95100 Catania, Italy
Giuseppe Nunnari, Infective Diseases, Department of Clinical and Molecular Biomedicine, Garibaldi Hospital of Nesima, 95100 Catania, Italy
Gaetano Bertino, Hepatology Unit, Department of Medical and Pediatric Science, University of Catania, Policlinico, 95100 Catania, Italy
Author contributions: Malaguarnera G, Nunnari G, Giordano M, Bertino G and Malaguarnera M contributed equally to this work; all authors designed and performed the research and wrote the paper.
Correspondence to: Maria Giordano, MD, Research Centre “The Great Senescence”, University of Catania, Cannizzaro Hospital, 829 Via Messina, 95100 Catania, Italy. maria-gior@hotmail.it
Telephone: +39-95-7262008 Fax: +39-95-7262011
Received: February 25, 2014
Revised: June 4, 2014
Accepted: July 11, 2014
Published online: November 28, 2014
Processing time: 280 Days and 6.3 Hours
Abstract

Alcoholic liver disease (ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.

Keywords: Alcoholic liver disease; Bacterial translocation; Dysbiosis; Prebiotics; Probiotics; Synbiotic; Gut microbiota; Endotoxin

Core tip: A close anatomical and functional relationship between gut and liver exists. Blood circulated in the portal vein transfers various toxic compounds for filtration by liver. Endotoxin is a lipopolysaccharide derived from the cell wall of Gram negative bacteria presents in the intestine, which is absorbed from intestinal epithelium and transported to the liver and Kupffer cells through the portal vein. A qualitative (dysbiosis) and quantitative (bacterial overgrowth) alteration of intestinal microbiome are the causes of an increase of endotoxins and subsequently, liver damage. The new treatments try to contrast dysbiosis and bacterial overgrowth decreasing evolution of alcohol liver disease.