Gut microbiome and intestinal barrier failure – The “Achilles heel” in hepatology?

Abstract

Bacterial translocation (BT) includes themigrationof viablemicroorganisms but also all microbial products (endotoxins such as lipopolysaccharide [LPS], lipoteichoic acid, bacterial DNA, peptidoglycans, and fragments, e.g. muramyldipeptide, etc.) across an even, anatomically intact intestinal barrier from the intestinal lumen tomesenteric lymph nodes (MLN) and other extraintestinal organs and sites [2]. Although the term ‘‘BT’’ summarizes all these various bacterial products, the route, and site as well as the immunological response between themaremost likely very different. BT in liver disease has been extensively studied in the past, mainly due to its long known role as an underlying mechanism in the development of spontaneous bacterial infections such as spontaneous bacterial peritonitis (SBP) in decompensated cirrhosis [17]. Moreover, in advanced cirrhosis, pathological BT most likely impacts on the natural course of liver cirrhosis via triggering and/ or aggravatinghepatic failure, encephalopathy or hepatorenal syndrome. On this background, it has been proposed that intestinal decontamination could improve disease severity in cirrhotic patients [7]. Concerning the mechanisms promoting BT in chronic liver disease, the majority of the studies have been performed in decompensated cirrhosis unraveling threemain factors: intestinal bacterial overgrowth (IBO), increased intestinal permeability (IP), and impaired immunity. IBO has usually been evaluated at only one site, namely the upper small intestine, by applying culture techniques since it is defined as >10 CFU/ml aspirate. However, it needs to be stressed that only a minority of the enteral flora can be cultured by conventional techniques andwhether the small intestine is the site of most prevalent translocation has not been addressed so far. Nonetheless, in advanced liver cirrhosis IBO is a very frequent finding and has been linked to the development of BT, endotoxemia, and SBP [1,12]. Indeed, bacteria causing SBP are not only normal commensal gut bacteria but most frequently exactly those overgrowing in the small intestine. So it has been said that BT is caused by ‘‘too much of the good guys at the wrong place’’ since, the upper intestine is not made to host this load of bacteria. Increases in IP in cirrhosis have been reported by various