When the equilibrium in the bowel is disturbed
The intestine is an important part of our immune system. Its protective layer, the intestinal epithelium, forms a barrier that decides which substances are allowed to enter the body and which are not. Essentially, it forms a protective barrier against the trillions of bacteria that live in the gut and ensures that they do not enter the body. However, scientists have discovered that intestinal flora communicate with the immune system, and interact with and influence each other. Around 70 percent of all immune cells in the human body are found in the intestinal wall under the epithelium.
A group of researchers led by Prof. Dr. Christoph Becker, Professor of Molecular Gastroenterology at FAU and Head of Research at the Department of Medicine 1 at Universitätsklinikum Erlangen and the Collaborative Research Centre TRR241 ‘Immune-Epithelial Communication in Inflammatory Bowel Diseases’ are investigating the fundamental processes behind abnormal communication between intestinal flora, the epithelium and immune cells. Becker and his team assume that these abnormal signalling pathways contribute to the development of chronic inflammatory bowel diseases (CIBD) such as Morbus Crohn or ulcerative colitis.
The interpreter in our intestines
The epithelial cells in our intestines work like interpreters as they translate the signals from the intestinal flora into signals the immune system can understand and vice versa. The immune system sends signals via the epithelial cells that directly or indirectly influence the intestinal flora. As a result, bacteria are destroyed or substances produced by the body are released that change the composition of the intestinal flora. The condition of the layer of mucus that covers the intestine can also change. ‘The signals of the immune system not only regulate the number of bacteria that live in the gut, but also which bacteria may live in which intestinal environment,’ says Becker.
The bacteria play a significant role in the maturity of the immune system – if the intestines are not colonised by bacteria, the immune system cannot develop properly. The signalling pathways that the epithelium passes on in order to keep all these processes in balance are not yet fully understood. ‘However, we believe that the function of the epithelium as an interpreter of the signals from the intestinal flora and the immune system is extremely important in order to maintain the equilibrium and ensure that the body remains healthy in a foreign and potentially hostile atmosphere,’ explains Becker.
A system out of balance
Bacteria can penetrate the intestinal barrier if the balance provided by the epithelium is thrown off track, causing the epithelium to use messengers to call on the immune system for help. The immune system detects the invaders and produces molecules that trigger inflammation. Whilst this is the normal process for killing off microorganisms, inflammation damages the epithelial cells and creates new gateways for bacteria to enter. The epithelium then produces more messengers in order to alert the immune system. If balance is not restored in the intestines, for example because the production of substances that promote inflammation is not stopped quickly enough due to disruptions to the signalling pathways, a self-perpetuating cycle ensues that can lead to chronic inflammatory bowel disease (CIBD), according to Becker.
Controlling cell death
According to the researchers at FAU, CIBD can also be triggered by a malfunction in cell death regulation. It is well known that apoptosis, a type of programmed cell death, is triggered in intestinal epithelium cells by high levels of activity of the enzyme caspase-8. If several cells are affected by apoptosis, this can cause damage to the intestinal barrier and contribute to the development of CIBD. Becker’s team assumed that this could be prevented by inhibiting caspase 8. However, they discovered the opposite is true. If caspase-8 was missing in the cells, this triggered a form of programmed cell death known as necroptosis that was discovered only a few years ago. The researchers are now investigating the influence of necroptosis on CIBD and other bowel diseases.
About the author
Simone Harland has been a freelance journalist and copywriter for 25 years. She writes for magazines, companies and publishing houses and lives by the sea.
FAU research magazine friedrich
This article first appeared in our research magazine friedrich. You can order the print issue (only available in German) free of charge at presse@fau.de.