The pathogenesis of these disease processes shows some Sunitinib supplier shared features, including inflammatory cell infiltration in liver tissue, elevated serum transaminases suggesting hepatocyte damage, and increased serum levels of pro-inflammatory cytokines. The proposed mechanisms of gut–liver interaction

in these diseases (Fig. 1) include alterations in composition of gut microbiota, small intestine bacterial overgrowth, increase in permeability of small bowel, and alterations in mucosal and systemic immunity. Relationship of gut flora with liver disease may be influenced by several other factors, such as diet, toxin exposure, environmental factors, and probably genetic predisposition of an individual. Further, the alterations in microbiota may influence not only the likelihood of liver disease, but also the rate of its progression or of the development of its complications. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of abnormalities, ranging from simple steatosis, characterized by excessive fat deposition in hepatocytes without

any inflammation or necrosis, to NASH characterized by steatosis-associated with liver inflammation. The condition is often associated BI-6727 with obesity and metabolic syndrome or its individual components. A proportion of individuals with NAFLD, particularly those with NASH, progress to liver cirrhosis and portal hypertension, and may carry an increased risk of HCC. Gut microbiota may be involved in the pathogenesis of NAFLD in several ways, namely predisposition to obesity, induction of insulin resistance, or induction of liver inflammation.[20] Relationship of gut flora with obesity is quite strong in mice, whose gut flora resembles that of humans in predominance of Firmicutes and Bacteroidetes. Progesterone GF mice resist development of obesity when fed a high-fat, high-sugar diet.[21] Introduction of gut flora in GF mice has been shown to lead to increased harvesting of energy from diet with increased intestinal monosaccharide uptake, development of insulin resistance, induction

of hepatic lipogenesis and fat deposition, and increased weight and body fat content.[22] More importantly, GF mice inoculated with gut flora from genetically obese mice harvest energy more efficiently and develop larger body fat stores than their control mates inoculated with gut flora from genetically lean mice.[23] Taken together, these animal studies strongly suggest a role for gut microbes in the development of obesity. This evidence is supported by human studies showing a relative excess of Firmicutes and reduction of Bacteroidetes in the gut flora of obese persons than those from lean persons.[24] In addition, reduction of weight in the former group was associated with partial restoration of gut bacterial composition to the lean pattern.[24, 25] However, the relationship of gut microbes with obesity and NAFLD is complex.