Intestinal barrier dysfunction in cirrhosis: Current concepts in pathophysiology and clinical implications

Abstract

The intestinal lumen is a host place for a wide range of microbiota and sets a unique interplay between local immune system, inflammatory cells and intestinal epithelium, forming a physical barrier against microbial invaders and toxins. Bacterial translocation is the migration of viable or nonviable microorganisms or their pathogen-associated molecular patterns, such as lipopolysaccharide, from the gut lumen to the mesenteric lymph nodes, systemic circulation and other normally sterile extraintestinal sites. A series of studies have shown that translocation of bacteria and their products across the intestinal barrier is a commonplace in patients with liver disease. The deterioration of intestinal barrier integrity and the consulting increased intestinal permeability in cirrhotic patients play a pivotal pathophysiological role in the development of severe complications as high rate of infections, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, variceal bleeding, progression of liver injury and hepatocellular carcinoma. Nevertheless, the exact cellular and molecular mechanisms implicated in the phenomenon of microbial translocation in liver cirrhosis have not been fully elucidated yet.

Microbiota dysbiosis: a new piece in the understanding of the carcinogenesis puzzle

“…HCC is one of the most frequently diagnosed human cancers worldwide, with 80-90 % of cases being preceded by chronic liver disease, liver fibrosis and cirrhosis (Roh & Seki, 2013). Most HCC cases have developed as the result of chronic hepatic inflammation (Fung et al, 2014;Tsiaoussis et al, 2015). Chronic liver disease is the result of several aetiologies, from alcohol consumption to viral infection, which are related to the increased risk of fibrosis, cirrhosis and liver failure (Fung et al, 2014;Roh & Seki, 2013).…”

“…It has been proposed that products derived from microorganisms, such as LPS, participate in the progression of HCC through the release of pro-inflammatory cytokines (Hines et al, 2010). Increased intestinal permeability, bacterial translocation and LPS accumulation activating the NFkB pathway suggest a hallmark of chronic liver disease and contribute to hepatic inflammation, proinflammatory cytokines TNF-a, IL-6 and IL-1 release, oxidative damage and fibrosis (Tsiaoussis et al, 2015).…”

Bacterial translocation in critical illness

“…Damage to the GIT epithelium can allow passage of bacteria and endotoxin to the liver via the portal circulation (Tsiaoussis et al . ). Endothelial cells in the wall of the liver sinusoids, Kupffer cells in the periportal area and liver‐resident lymphocytes clear organisms and microbial products from the portal venous circulation (Jenne & Kubes ).…”

“…2015 ). Damage to the GIT epithelium can allow passage of bacteria and endotoxin to the liver via the portal circulation (Tsiaoussis et al . 2015 ).…”

NMR‐based urinary profiling of lactulose/mannitol ratio used to assess the altered intestinal permeability in acute on chronic liver failure (ACLF) patients

“…[6,8] The deterioration of intestinal epithelial barrier integrity in cirrhotic patients and the resulting altered IP plays a major pathophysiological role in the development of this medical emergency. [9,10] However so far, there are no prospective follow-up studies showing altered IP in patients with ACLF and if this altered IP resets back to normal in clinically improved patients-assessed based on Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) score. [11,12] Further, there are no well-established prognostic indicators available for predicting ACLF progression or outcome of a treatment.…”