18 On the other hand, if bacterial overgrowth is induced experimentally in the small intestine, this causes liver inflammation and injury.40 We speculate that activation of the mucosal innate immune system, as demonstrated by increased levels of Reg3b and Reg3g, contributes to reduced intestinal bacterial overgrowth in Muc2−/− mice. Prebiotics restore Reg3b and Reg3g expression, limit bacterial overgrowth and ameliorate alcohol-induced steatohepatitis.28 However, other antimicrobial molecules or components of

the mucosal innate immune system might work in concert with Reg3b and Reg3g, and future studies are required for further investigations. Thus, based on our study, we propose a concept in which NVP-LDE225 suppression of intestinal bacterial overgrowth by host antimicrobial molecules results in a decreased availability learn more of intraluminal bacterial products. Less of these products are able to cross the intestinal barrier into the portal circulation, which eventually limits alcoholic liver disease. We have also recently demonstrated qualitative changes in the enteric microbiome (dysbiosis) using a model of intragastric

alcohol feeding in mice. Alcohol-associated dysbiosis is characterized by a profound suppression of commensal probiotic bacteria, including Lactobacillus.28 Several studies have shown that a restoration of eubiosis using supplemental probiotic Lactobacillus ameliorates alcoholic steatohepatitis in rodents.41, 42 Interestingly, Muc2−/− mice are protected from alcohol-associated changes in the microbial composition, including a suppression of Lactobacillus. In addition, Muc2 deficiency limits the proliferation of bacteria (such as

gram-negative A. muciniphila) that use mucins as carbon source. Thus, the absence of Muc2 prevents alcohol-associated dysbiosis, restores intestinal homeostasis, and inhibits experimental alcoholic liver disease. selleck inhibitor The mucus layer has a very important role in the intestine. It largely prevents the translocation of viable bacteria from the gut lumen to extraintestinal organs such as lymph nodes and the systemic circulation.43 The absence of Muc2 as a major component of the intestinal mucus layer has no obvious adverse effect for the gut-liver axis at baseline without challenge. The thickness of the mucus layer increases in alcoholics as shown in our study and by others in rodents,27 which could be interpreted as a defense against alcohol or more likely against intestinal epithelial cell injury. And indeed, enteric infections also increase the Muc2 production and the mucus layer.43 A downside of this obvious good reaction of the intestine of increasing the mucus layer is that the vigorous immune defense system of enterocytes against bacteria is impaired.