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World J Gastroenterol. Nov 14, 2014; 20(42): 15518-15531
Published online Nov 14, 2014. doi: 10.3748/wjg.v20.i42.15518
Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease
Giulia Paolella, Claudia Mandato, Luca Pierri, Marco Poeta, Martina Di Stasi, Pietro Vajro
Giulia Paolella, Luca Pierri, Marco Poeta, Martina Di Stasi, Pietro Vajro, Department of Medicine and Surgery, University of Salerno, 84081 Baronissi (Salerno), Italy
Claudia Mandato, Pediatrics of AORN Santobono-Pausilipon, 80123 Naples, Italy
Pietro Vajro, ELFID European Laboratory for the Investigation of Food Induced Disease, 80138 Napoli, Italy
Author contributions: Paolella G and Mandato C contributed equally and prepared the first draft of the manuscript with Vajro P; Mandato C, Paolella G, Pierri L, Di Stasi M and Poeta M carried out the bibliographical search; Vajro P was the guarantor of the manuscript, as well as supervising and revising the manuscript; All authors read and approved the final version of the manuscript.
Supported by (in part) FARB-ex 60% 2012 of the University of Salerno grant to Vajro P
Correspondence to: Pietro Vajro, Professor, Chair of Pediatrics, Department of Medicine and Surgery, University of Salerno, via Allende, 84081 Baronissi (Salerno), Italy. pvajro@unisa.it
Telephone: +39-89-672409 Fax: +39-339-2361008
Received: December 28, 2013
Revised: April 29, 2014
Accepted: July 15, 2014
Published online: November 14, 2014
Abstract

The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.

Keywords: Probiotics, Gut-liver axis, Intestinal microbiota, Barrier function, Small intestinal bacterial overgrowth, Bacterial translocation, Non-alcoholic fatty liver disease

Core tip: Modulation of gut microbiota by probiotics is supported by a number of studies conducted with non-alcoholic fatty liver disease animal models and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising add-on therapeutic tool to be used in the context of a tailored multi-target therapy especially in cases where standard dietary and lifestyle changes have failed.