Review
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World J Gastroenterol. Jun 7, 2012; 18(21): 2609-2618
Published online Jun 7, 2012. doi: 10.3748/wjg.v18.i21.2609
Leaky gut and the liver: A role for bacterial translocation in nonalcoholic steatohepatitis
Yaron Ilan
Yaron Ilan, Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
Author contributions: Ilan Y wrote the review.
Supported by Immuron, Nasvax, Plantylight, Desert Labs, Teva Pharmaceutical and ENZO Biochem
Correspondence to: Yaron Ilan, MD, Gastroenterology and Liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel. ilan@hadassah.org.il
Telephone: +972-2-6778231 Fax: +972-2-6431021
Received: June 19, 2011
Revised: January 31, 2012
Accepted: April 21, 2012
Published online: June 7, 2012
Abstract

Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.

Keywords: Nonalcoholic steatohepatitis; Bacterial translocation; Insulin resistance; Leaky gut; Lipopolysaccharide