Pathological bacterial translocation in liver cirrhosis

Humans harbor nearly 100 trillion intestinal bacteria, which in terms of numbers, represents around ten times more microbial cells than eukaryotic cells. The gastrointestinal (GI) tract, the largest surface area of the body with an epithelial surface of approximately 400 m, is in constant exposure to these live microorganisms. Their peaceful coexistence demonstrated by the lack of pro-inflammatory responses against commensal bacteria implicates the presence of clearly defined lines of communication. In fact, bacterial translocation (BT), being defined as translocation of bacteria and/or bacterial products (lipopolysaccharides, peptidoglycans, muramyl-dipeptides, bacterial DNA, etc.) from the gut to mesenteric lymph nodes (MLN) [1], is a physiological process in healthy conditions and crucial for host immunity. In contrast, in cirrhosis ‘‘pathological’’ BT develops with a sustained increase in quantity (rate and/or degree) of BT. However, at least in humans, lack of access to MLN and/or upstream compartments towards the mucosal barrier until now hamper establishment of ‘‘cut-off’’ levels for physiological levels of BT in individual patients. Nonetheless, there appears to exist a hierarchy of three barriers against pathological BT, each of which encompasses a distinct set of mechanisms (Fig. 1). First, there are mediators that limit direct contact between the intestinal bacteria and the epithelial cell surface. Secondly, a layer of immune protection involves the rapid detection and killing of bacteria that manage to penetrate. Finally, a set of immune responses minimizes exposure of bacteria to the systemic immune system. In advanced liver cirrhosis, at each of these