Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg

Hepatol Int. 2018 Feb;12(Suppl 1):24-33. doi: 10.1007/s12072-017-9798-x. Epub 2017 May 26.

Abstract

The term gut-liver axis is used to highlight the close anatomical and functional relationship between the intestine and the liver. The intestine has a highly specialized epithelial membrane which regulates transport across the mucosa. Due to dysbiosis, impairment of the intestinal barrier and altered immunity status, bacterial products can reach the liver through the portal vein, where they are recognized by specific receptors, activate the immune system and lead to a proinflammatory response. Gut microbiota and bacterial translocation play an important role in the pathogenesis of chronic liver diseases, including alcoholic and non-alcoholic fatty liver disease, cirrhosis, and its complications, such as portal hypertension, spontaneous bacterial peritonitis and hepatic encephalopaty. The gut microbiota also plays a critical role as a modulator of bile acid metabolism which can also influence intestinal permeability and portal hypertension through the farnesoid-X receptor. On the other hand, cirrhosis and portal hypertension affect the microbiota and increase translocation, leading to a "chicken and egg" situation, where translocation increases portal pressure, and vice versa. A myriad of therapies targeting gut microbiota have been evaluated specifically in patients with chronic liver disease. Further studies targeting intestinal microbiota and its possible hemodynamic and metabolic effects are needed. This review summarizes the current knowledge about the role of gut microbiota in the pathogenesis of chronic liver diseases and portal hypertension.

Keywords: Bile acids; Cirrhosis; Endotoxemia; Gut–liver axis; LPS; Microbiota; Portal hypertension; Translocation.

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Bacterial Infections / complications
  • Bacterial Translocation / genetics
  • Bile Acids and Salts / metabolism
  • Endotoxemia / etiology
  • Endotoxemia / metabolism
  • Fecal Microbiota Transplantation / adverse effects
  • Fecal Microbiota Transplantation / methods
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Hepatic Encephalopathy / complications
  • Hepatic Encephalopathy / microbiology
  • Humans
  • Hypertension, Portal / etiology*
  • Hypertension, Portal / metabolism
  • Hypertension, Portal / microbiology
  • Intestinal Mucosa / metabolism
  • Intestines / microbiology*
  • Lipopolysaccharide Receptors / metabolism
  • Liver / metabolism*
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / therapy
  • Liver Diseases / metabolism
  • Liver Diseases / physiopathology*
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / prevention & control
  • Non-alcoholic Fatty Liver Disease / therapy
  • Peritonitis / microbiology
  • Probiotics / therapeutic use
  • Receptors, Cytoplasmic and Nuclear / metabolism

Substances

  • Adrenergic beta-Antagonists
  • Bile Acids and Salts
  • Lipopolysaccharide Receptors
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor