. Scientific Frontline: Attack from the intestine

Thursday, March 23, 2023

Attack from the intestine

After an operation, bacteria can enter the organism from the intestine. Combat special cells of the immune system that are located in the liver.
Illustration Credit: Mercedes Gomez de Agüero

Darmbacteria are more common triggers of complications after surgery. This is shown by a new study by research teams from Würzburg and Bern. A solution to this problem could come from the liver.

German hospitals carried out almost 16 million operations in 2021. In Switzerland there are around 1.1 million. Even if the actual procedure is going well, it is not uncommon for a wound infection to occur afterwards, which can have dramatic consequences for those affected. In extreme cases, such infections are fatal.

A new study now shows that the causes of these infections are in a large part of the cases bacteria from the patient's intestine itself. To do this, the intestine does not even have to be injured during the operation. In this way, too, these pathogens overcome the intestinal barrier postoperatively and spread throughout the body through the blood and lymphatic pathways. They can be stopped by special immune cells that patrol all organs, including the liver.

This study was published in the current issue of the trade journal Cell reports. Professor Guido Beldi, chief physician visceral surgery at the University Clinic for Visceral Surgery and Medicine at the Inselspital in Bern, and Dr. Mercedes Gomez de Agüero, head of a junior research group at the Institute for Systems Immunology at the Julius Maximilians University in Würzburg (JMU).

“It has long been known that accompanying infections increase mortality invasive procedures. For this reason, extensive hygiene and asepsis measures are carried out to eliminate microorganisms in the field of operation,” explains Guido Beldi. However, as it now turns out, the danger comes from a completely different corner: the patient's intestine.

100 trillion microorganisms live in the intestine

“In the human intestine, several hundred strains of different bacteria live with around one hundred trillion microorganisms. They form the natural intestinal flora, also called the microbiome,” explains the participating scientist Gomez de Agüero. Their existence is an advantage for humans: they help with digestion, eliminate pathogens and train the immune system. However, this only applies as long as these bacteria do not overcome the so-called intestinal barrier and spread in the body.

After an operation, however, this can happen: "In our study, we analyzed the microorganisms that caused concomitant infections in almost 4,000 patients after a major surgical procedure," explains Guido Beldi. It was found that in almost all cases the pathogens were bacteria from the patient's intestine, such as Enterococcus, Escherichia coli and Clostridium.

These most often caused infections after surgery on the liver, pancreas and biliary tract, as well as during operations on the small and large intestine. Patients in particular who had to undergo a large liver resection - i.e. the removal of large parts of the liver - suffered such an infection, which significantly delayed the healing process.

Important actors sit in the liver

That the liver actually plays a special role in this infection, the researchers were able to demonstrate in the mouse model: “We know, that special cells of the immune system, who are resident in the liver, are responsible for the control of these spreading bacteria and for the healing process after major operations”, says Gomez de Agüero. They are a group of lymphocytes, the so-called "Innate Lymphoid Cells" (ILCs), which are important players in the innate immune system.

If bacteria get from the intestine into the liver via the blood flow, these ILCs are activated and release special messenger substances, such as interleukin 22, a protein that can trigger and regulate immune reactions. In this way, they stimulate liver cells to produce antimicrobial substances. "In this way, congenital lymphatic cells located in the liver control the systemic spread of intestinal bacteria and effectively combat accompanying infections after operations," said the scientist.

"The strengthening of immunity is therefore a sensible prophylactic and therapeutic alternative strategy to the usual antimicrobial therapies to prevent accompanying infections after operations," Guido Beldi suggests. At least until it is clear which factors are responsible for the fact that after an operation, the intestinal barrier no longer prevents intestinal bacteria from penetrating the interior of the body. The research team now wants to investigate these questions.

Published in journalCell reports

Source/CreditUniversity of Würzburg | Gunnar Bartsch

Reference Number: mcb032323_02

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