Researchers at KU Leuven have discovered that specific immune cells in the gut play a crucial role in the development of bacterial infections in liver cirrhosis. The findings help explain why patients with liver cirrhosis are so susceptible to infections and open the door to research into how these infections can be prevented. The results of the study were published in Gut.

Liver cirrhosis affects millions of people worldwide and is a common cause of death. Patients with liver cirrhosis are susceptible to bacterial infections, which usually originate in the gut. When gut bacteria enter the liver and bloodstream, they can cause severe liver damage and organ failure. Until now, it was unclear exactly how these bacteria breach the intestinal barrier and reach the liver.

A team of KU Leuven researchers led by Professor Schalk van der Merwe, Professor Guy Boeckxstaens and research coordinator Hannelie Korf investigated which factors play a role in breaching the intestinal barrier. In collaboration with international partners, they studied both mouse models and intestinal samples from people with liver cirrhosis.

We can conclude that not only does the intestinal wall itself form a barrier against gut bacteria, but that the immune cells within it also play an important role.

Research coordinator Hannelie Korf

Weakened immune cells clear the way for bacteria

The study focused on macrophages, a type of immune cell located in the walls of intestinal blood vessels. These cells destroy bacteria that escape from the gut, preventing them from spreading further throughout the body. The intestines contain millions of bacteria that are essential for healthy digestion but can cause infections if they reach other parts of the body.

In mice with liver cirrhosis, these protective immune cells were found to function less effectively: they destroyed fewer gut bacteria, communicated less effectively with surrounding cells, and lost their fixed position along the blood vessels. As a result, gut bacteria could enter the bloodstream more easily and spread to other parts of the body, including the liver.

This is particularly harmful for patients with liver cirrhosis. A bacterial infection can cause severe liver damage more rapidly in these patients and can also lead to the failure of other organs.

Researcher Lena Smets

Also observed in patients

The findings in mice were confirmed in people with liver cirrhosis. By analysing intestinal samples from patients, the researchers found that blood vessel-associated macrophages were also disrupted in humans.

“We now have a better understanding of why bacteria can spread throughout the body in patients with liver cirrhosis,” says Professor of Hepatology Schalk van der Merwe. “Our results show that strengthening these immune cells is important for restoring the intestinal barrier and protecting patients from life-threatening infections.”

A simple infection can quickly escalate into organ failure or hospitalisation in people with liver cirrhosis. For this vulnerable group of patients, every infection poses a major risk. Identifying the cause of these infections is a major step in the right direction.

Researcher Maria Viola

More information

• The study, “Intestinal blood vessel-associated macrophages and gut-vascular barrier dysfunction in cirrhosis” by Smets et al., was published in the journal Gut (doi: 10.1136/gutjnl-2025-335745). The research was supported by, among others, the FWO, KU Leuven, the German Research Foundation, the Swiss National Science Foundation and an ERC Advanced Grant.
• The team consisted of researchers from KU Leuven, the Flanders Institute for Biotechnology (VIB), the University of Basel, Humanitas University in Milan, the Cardiovascular Research Institute Maastricht, IfADo in Dortmund and South Valley University in Egypt.
• KU Leuven conducts fundamental and translational scientific research that also involves the use of laboratory animals. Studies seeking to use laboratory animals must first receive approval from an ethics committee, which carefully reviews each application. More information is available on KU Leuven’s policy regarding scientific research involving laboratory animals.

Image: liver cirrhosis

Blood vessel (red) with macrophages (green). The immune cells are located farther away from the blood vessel and are no longer closely attached to it, disrupting the immune barrier. © KU Leuven

Source: KU Leuven – University of Leuven