Useful intestinal germ can also make you sick

Researchers are discovering new triggers of chronic intestinal inflammation

Permeable protective barrier: If the sealing protein E-cadherin (light green) is missing, it causes intestinal inflammation (right). © TU Munich
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Researchers have discovered why a normally useful intestinal germ makes some people ill: The bacterium Enterococcus faecalis produces an enzyme that is harmless to healthy people. However, if a person has a genetic susceptibility to bowel inflammation, the enzyme perforates their intestinal mucosa and triggers such chronic inflammatory bowel disease as Crohn's disease and ulcerative colitis.

This previously unknown interaction between beneficial intestinal bacteria, genetic predisposition and the onset of the disease has been elucidated by scientists of the Technical University of Munich (TUM) in mice. As they report in the journal "Gastroenterology", they now want to develop new treatments for inflammatory bowel disease based on these findings.

Many riddles about Crohn's disease and ulcerative colitis

The newly discovered mechanism is helping to better understand the complex causes of chronic inflammatory bowel disease, researchers say. Because how Crohn's disease and ulcerative colitis in humans, is still largely unexplained. Although it is known that about 100 genes or gene segments increase the susceptibility to it. Whether the disease actually breaks out, however, can not be reliably deduced from this.

"In the development of chronic intestinal inflammation, the complex interaction between the genetic predisposition and the microbial environment in the intestine is crucial, " says study director Dirk Haller of the Technical University of Munich. Other trigger factors are also a weakness of the immune system or certain dietary habits. The fact that the enzyme gelatinase produced by the intestinal germ Enterococcus faecalis plays an important role in the onset of chronic intestinal inflammation has now been established for the first time in experiments on mice.

Track the bacterial enzyme traced in the mouse gut

For their study, the researchers followed the path of the produced by Enterococcus faecalis enzyme gelatinase in the intestine of mice: In healthy mice, it proved to be safe for the intestinal mucous wall. However, it is different in genetically modified mice with an increased susceptibility to intestinal inflammation: Here, the enzyme attacks certain molecules in the intestinal wall. These sit like glue between the mucosal cells of the intestine and seal the tissue. If they are destroyed, this makes the intestinal wall permeable, say the scientists. display

Upon breakthrough of the protective barrier, the immune system of the mouse reacts with inflammation, as the researchers report. These, in turn, weaken the intestinal wall, opening the door for further germs. Chronic diseases are the result.

The next step is research with humans

The researchers now want to make the new findings from the mouse experiments applicable to medicine. Next, they plan to study the effect of gut bacteria and their enzyme in treating patients with chronic bowel disease. This should be done in cooperation with the Klinikum rechts der Isar of the University of Munich.

The aim of the scientists in this follow-up project is to develop new methods to inhibit the enzyme production of Enterococcus faecalis bacteria. If so, such an approach could help prevent the onset of chronic bowel disease in genetically susceptible humans.

Darmkeim with health-promoting effect

At one trillion bacteria per square meter, the human gut is the most densely populated ecosystem. Its inhabitants include Enterococcus faecalis, a lactic acid bacterium found in fermented cheese and sausages. In probiotic foods this germ is even attributed a health-promoting effect.

"Bacteria, such as Enterococcus faecalis, have an invigorating effect on both sides: they can increase or promote the diseases, " explains Haller. The direction in which the pendulum swings depends also on the genetic make-up of the host organism. (Gastroenterology, 2011; doi: 10.1053 / j.gastro.2011.05.035)

(Gastroenterology / dapd, 01.12.2011 - NPO)