The liver is constantly exposed to gut microbiota-derived products that activate hepatic toll-like receptor 4 (TLR4), which has been implicated in the development of liver inflammation and fibrosis, and even hepatocellular carcinoma [5,6]. Obese subjects present distinct microbiota composition with relative low proportion of Bacteroidetes and predominance of Firmicutes . This predominance has been associated with a propensity to develop NAFLD features, such as fasting hyperglycemia, hyperinsulinemia, hepatic steatosis, and increased expression of genes involved in de novo lipogenesis, independently of the presence of obesity, in animals models . The microbiota composition of humans with NASH also presents lower proportion of Bacteroidetes independently of BMI and dietary fat intake. The low prevalence of Bacteroidetes may facilitate the development of other bacteria phyla that are more efficient in harvesting energy from the diet .
NAFLD patients present a high prevalence of small intestine bacterial overgrowth (SIBO) [10,11,12,13,14] and increased gut permeability [13,15] characterized by disruption of the intercellular tight junctions, which is likely to be the underlying mechanism of translocations of bacteria and their products . NASH subjects have elevated plasma levels of LPS associated with a rise in tumor necrosis factor (TNF)-α gene expression in the hepatic tissue, which supports a role of endotoxemia in the development of steatohepatitis . SIBO in NASH individuals is also associated with enhanced hepatic expression of TLR4 and release of interleukin (IL)-8 supporting the hypothesis that SIBO may have an important role in NASH development and progression .