One possibility is that bacterial ligands are not as accessible to enterocytes to stimulate the expression of antimicrobials. Reg3g expression has been shown to be TLR5 and IL-22–dependent and can be induced by flagellin,34, 44, 45 but intestinal IL-22 did not correlate with Reg3 protein expression in our study. Indeed, Reg3g expression

is induced through cell-autonomous MyD88-dependent TLR activation in intestinal Paneth cells.46 Thus, when the body is challenged with alcohol, the thickness of the intestinal mucus layer increases, and less antimicrobial molecules reach the lumen to control proliferation of intestinal bacteria. An apparently good reaction of the body to respond to alcohol-induced epithelial cell damage impairs the mucosal PLX-4720 in vitro innate immune system and results in the intestinal homeostasis system to fail. One should note that this is not a general response in Muc2-deficient mice upon intestinal injury or inflammation, but is rather specific for alcohol. Other studies have shown that colitis induced selleck screening library by the pathogen Citrobacter rodentium is exacerbated in Muc2-deficient mice.43 Our study demonstrates that deficiency of one host gene Muc2 that is not expressed in the liver or in inflammatory cells, but largely restricted to the intestine, decreases alcoholic steatohepatitis. Our findings

are consistent with the large body of evidence that experimental alcoholic liver disease is driven by the gut. Alcohol-associated changes in the microbiome, and in particular intestinal bacterial overgrowth, contributes to

alcohol-induced liver injury. Taken together, our study emphasizes again the importance of the gut-liver axis. Treatment targeting the mucosal innate immune system and intestinal bacterial overgrowth might contribute to the clinical management of alcohol-induced liver disease. We thank Akiko Ueno and Raul Lazaro from the Animal Core facility of the Southern California Research Center 上海皓元 for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, University of Southern California, for performing animal studies described in this study. We also thank Derick Han for tissue sharing and Yaron Niv and Anna Velcich for helpful discussion and careful reading of the manuscript. Additional Supporting Information may be found in the online version of this article. “
“Aim:  Diabetes mellitus (DM) has been reported to worsen the long-term prognosis of cirrhotic patients, and many studies have reported that DM is an independent risk factor for hepatocellular carcinoma. However, an accurate diagnosis of DM is sometimes difficult in cirrhotic patients. Recently, a novel non-invasive 13C-glucose breath test has been reported to be useful for diagnosing insulin resistance in non-cirrhotic patients. The aim of this study was to evaluate the efficacy of this tool for the identification of DM in cirrhotic patients.