Leaky gut and gut-liver axis in liver cirrhosis: Clinical studies update

Abstract

Portal blood flows into the liver containing the gut microbiome and its products such as endotoxin and bacterial DNA. The cirrhotic liver acts and detoxifies as the initial site of microbial products. In so-called "leaky gut," the increased intestinal permeability for bacteria and their products constitutes an important pathogenetic factor for major complications in patients with liver cirrhosis. Prolonged gastric and small intestinal transit may induce intestinal bacterial overgrowth, a condition in which colonic bacteria translocate into the small gut. Cirrhotic patients further show gut dysbiosis characterized by an overgrowth of potentially pathogenic bacteria and a decrease in autochthonous nonpathogenic bacteria. Pathological bacterial translocation (BT) is a contributing factor in the development of various severe complications. Bile acids (BAs) undergo extensive enterohepatic circulation and play important roles in the gut-liver axis. BT-induced inflammation prevents synthesis of BAs in the liver through inhibition of BA-synthesizing enzyme CYP7A1. A lower abundance of 7α-dehydroxylating gut bacteria leads to decreased conversion of primary to secondary BAs. Decreases in total and secondary BAs may play an important role in the gut dysbiosis characterized by a proinflammatory and toxic gut microbiome inducing BT and endotoxemia, as addressed in my previous reviews. Selective intestinal decontamination by the use of various antimicrobial drugs for management of complications has a long history. Lactobacillus GG decreasing endotoxemia is reported to improve the microbiome with beneficial changes in amino acid, vitamin and secondary BA metabolism. Current approaches for hepatic encephalopathy are the use of nonabsorbable antibiotics and disaccharides. Probiotics may become an additional therapeutic option for advanced liver cirrhosis.