Uncovering the interplay between gut microbiota and the immune system in cirrhotic patients (TIPINF)
Bacterial infections are one of the most severe complications in patients with decompensated liver cirrhosis. The immune system of this patient group is weakened due to a complex dysfunction of the immune system (cirrhosis-associated immune dysfunction, CAID). The cause of the immune system dysfunction is mainly due to the fact that the liver is severely damaged and the patients also suffer from continuous systemic inflammation. This, in turn, leads to a fourfold increased risk of bacterial infections. Infections are the most common trigger of acute liver decompensation in people with cirrhosis. The main factor for systemic inflammation and bacterial infections in liver cirrhosis is an increased migration of intestinal bacteria and their metabolic products through the intestinal wall into the blood.
It is assumed that an unfavourable change (dysbiosis) in the composition of the intestinal microbiome plays a crucial role here: the colonisation of (potential) pathogens is favoured, the intestinal mucosa is damaged and the balance of the immune system is altered.
Another very important trigger is portal hypertension in the liver. In addition to liver transplantation, the insertion of a permanent artificial connection between the portal vein and the hepatic vein, known as a transjugular intrahepatic portosystemic shunt (TIPS), is considered an effective treatment. Shortly after TIPS insertion, infections remain a critical risk for about half of the patients. The long-term effects of reduced portal hypertension on cirrhosis-associated immune dysfunction, systemic inflammation and the risk of bacterial infection have not yet been studied in detail, and the role of the gut microbiota in this context is unknown. In the study, the researchers will investigate the relationships between the composition and function of the gut microbiota and the risk of infection and other complications associated with cirrhosis after TIPS implantation. In addition, they will examine the extent to which treatment of portal hypertension with a TIPS leads to changes in systemic inflammation and the composition of the gut microbiota, and whether these changes affect the immune status.
