The microbiota in cirrhosis and its role in hepatic decompensation

Abstract

Cirrhosis - the common end-stage of chronic liver disease - is associated with a cascade of events, of which intestinal bacterial overgrowth and dysbiosis are central. Bacterial toxins entering the portal or systemic circulation can directly cause hepatocyte death, while dysbiosis also affects gut barrier function and increases bacterial translocation, leading to infections, systemic inflammation and vasodilation, which contribute to acute decompensation and organ failure. Acute decompensation and its severe forms, pre-acute-on-chronic liver failure (ACLF) and ACLF, are characterised by sudden organ dysfunction (and failure) and high short-term mortality. Patients with pre-ACLF and ACLF present with high-grade systemic inflammation, usually precipitated by proven bacterial infection and/or severe alcoholic hepatitis. However, no precipitant is identified in 30% of these patients, in whom bacterial translocation from the gut microbiota is assumed to be responsible for systemic inflammation and decompensation. Different microbiota profiles may influence the rate of decompensation and thereby outcome in these patients. Thus, targeting the microbiota is a promising strategy for the prevention and treatment of acute decompensation, pre-ACLF and ACLF. Approaches include the use of antibiotics such as rifaximin, faecal microbial transplantation and enterosorbents (e.g. Yaq-001), which bind microbial factors without exerting a direct effect on bacterial growth kinetics. This review focuses on the role of microbiota in decompensation and strategies targeting microbiota to prevent acute decompensation.

Keywords: Acute decompensation; Acute-on-chronic liver failure; Cirrhosis; Gut-liver-axis; Portal hypertension.

Figure 1.. Microbiome and decompensated cirrhosis.

Changes during progression of liver cirrhosis affect to a large extent the microbiota. Especially alcohol and diet, decreased bile flow, portal hypertension and activation of sympathetic nervous system impair gut motility and permeability, lead to decreased diversity, but increased bacterial load and bacterial overgrowth, dysbalance in bacterial species and finally increased bacterial translocation.

Figure 2. Microbiome and hepatic decompensation.

Worsening of liver disease initiates a cascade of events with intestinal bacterial overgrowth and dysbiosis as central events. Intestinal dysbiosis contributes to gut barrier function via several mechanisms. Increases bacterial translocation leads to upregulation of systemic inflammation and infections, vasodilation and contributes to hepatic decompensation and multi organ failure. Toxins produced by the microbiota can directly cause hepatocyte death and worsening of liver function.