The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension

Abstract

Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension.

Keywords: Bacterial translocation; Kupffer cell; Leaky gut; Lipopolysaccharide; Toll-like receptor.

Figure 1

Schematic presentation of the gut-liver axis and bacterial translocation. In normal condition, bacterial translocation from the gut to the liver is effectively prevented by gut barrier function. Furthermore, although small amount of bacteria or its products, such as lipopolysaccharide (LPS), can enter into the liver, they are rapidly removed by cleansing and detoxifying function of the liver. Therefore, activation of the immune cells and subsequent induction of inflammation is effectively prevented. However, in the pathologic condition, bacterial translocation is increased by impaired barrier function, bacterial overgrowth, and compositional change of gut flora (the increase of pathologic bacteria). Therefore, large amount of LPS can enter into the liver and induce immune cell activation and inflammation. In liver immune cells, particularly in the Kupffer cells, LPS induces proinflammatory pathway via TLR4 to produce proinflammatory cytokines, chemokines, and interferons.