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Bacterial factor can interfere with the protective layer in the intestine

22.11.2017

Human enzyme regulates detachment of the mucus layer in the intestine

The inside of the human intestine is covered with a vital protective layer of mucus. In addition, around 1,000 different species of bacteria live in the intestine, which are essential for human health. The interaction between bacteria and their human hosts is increasingly the focus of scientific research. Because the "communication" between the two sides changes under the influence of diet, illness and medication - but also with increasing age. Christoph Becker-Pauly, Professor at Kiel University and a member of the Cluster of Excellence "Inflammation at Interfaces", investigates the molecular interface between humans and bacteria.

If the balance between "good" and "bad" bacteria in the gut is disturbed, then serious diseases can result, because diverse bacterial colonization of the intestine is essential for us humans. There is an enzyme in the intestine, a so-called metalloprotease named Meprin β. This enzyme is found on the surface of intestinal cells in organisms. Its normal function is to cleave certain proteins - for example, growth factors and their receptors - which are also anchored in the cell membrane. In this way, Meprin β releases protein fragments into the cell surroundings, which can trigger a response from the immune system. This is a completely normal and natural process - as long as it occurs with a not too high or not too low intensity. Meprin β is also present in the intestine as a soluble enzyme. In this form, it cleaves certain proteins (mucins) in the mucus layer, and thus ensures the important renewal of the mucosal barrier. The amount of soluble and membrane-bound Meprin β is strictly regulated.

In a recent publication in Cell Reports, the Kiel biochemist Becker-Pauly, a member of the Collaborative Research Centre (CRC) 877 "Proteolysis as a Regulatory Event in Pathophysiology", together with experts from Germany, the United States and Sweden, examined how Meprin β regulates the structure of the intestinal mucosal barrier. "If this enzyme is not converted into the soluble form in sufficient quantities, then renewal of the mucus layer in the gut only occurs to a limited extent," explained Becker-Pauly. This means that the mucus layer becomes too thick, which creates an ideal breeding ground for bad bacteria. Chronic inflammatory bowel disease, which is one of the priority research areas of the Cluster of Excellence "Inflammation at Interfaces", may be the result.

The team led by Becker-Pauly discovered that Meprin β is regulated by a complex interplay of different human enzymes. "In the current study, we were able to show that a certain factor of the 'good' microbiome can favor the dissolution of Meprin β from the cell surface. Interestingly, however, the enzyme of a disease-causing bacteria was able to prevent precisely this step. This, of course, has consequences for the renewal of the mucus layer in the intestine," said the biochemist Becker-Pauly.

Today, the complex interaction of bacteria living in the body with the human metabolism is considered to be a key to understanding the development of illnesses such as chronic inflammatory bowel disease. The microbiome, i.e. the community of bacteria living in and on humans, is therefore a very interesting topic for research in this field. We know that certain bacterial compositions can tend to encourage the development of Crohn's disease, for example, while others more prevent the emergence of this disease. But is it really the composition of the microbiome which can cause disease? Or is it rather the interaction between bacteria and their human host that is decisive? Scientists from around the world are trying to understand the complex relationship between these two aspects. "Our findings provide useful information towards understanding molecular interactions between bacteria and their human host organism. Further studies within the framework of the Cluster of Excellence "Inflammation at Interfaces" and the CRC 877 will show whether and how these findings are beneficial to patients," concluded Becker-Pauly.

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More information:
Current publication by Prof. Becker-Pauly in “Cell Reports”:
http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31550-4

Collaborative Research Centre (SFB) 877 at Kiel University:
www.uni-kiel.de/Biochemie/sfb877/


The bacterial colonization of the human intestine regulates the ratio of the enzyme Meprin β in its soluble and membrane-bound forms. Only soluble Meprin β can - after its activation - cleave mucus proteins and thereby regulate and renew the mucus layer of the intestine. Disease-causing bacteria (pathogens) prevent the release of Meprin β from the cell surface, so that the mucus layer can no longer be renewed. The bacteria use the thick layer of mucus as a breeding ground and can thus trigger inflammatory bowel diseases.
Image: Rielana Wichert and Christoph Becker-Pauly
Dr Rielana Wichert, first author of the Cell Reports study, working with a confocal microscope. The monitor shows tissue samples taken from the small intestine, which are highlighted in color using fluorescent antibodies against two proteins. The mucosal protein (MUC2), which is located above the cell membrane, is colored green. The enzyme Meprin β investigated in this study is colored red, and is localized on the surface of the intestinal epithelial cells, so that it is in close proximity to the layer of mucus. The nuclei of the intestinal cells are colored blue, and show the typical structure of the intestinal epithelium consisting of villi and crypts.
Photo: Christoph Becker-Pauly



Press contact:
Dr Tebke Böschen
Tel.: +49 (0)431 880-4682, e-mail: tboeschen@uv.uni-kiel.de
Website: www.inflammation-at-interfaces.de



The Cluster of Excellence "Inflammation at Interfaces" has been promoted since 2007 by the Excellence Initiative of the Federation and the German States with a total budget of 68 million euros; currently, it is in its second phase. The 300 cluster members at four locations in Kiel (Kiel University, University Medical Center Schleswig-Holstein), Lübeck (Universität zu Lübeck, UKSH), Plön (Max-Planck-Institute for Evolutionary Biology) and Borstel (Research Center  Borstel - Leibniz-Center for Medicine and Biosciences) conduct research in an innovative, systemic approach to the phenomenon of inflammation, which can invade all barrier organs such as intestines, lungs and skin.

Cluster of Excellence Inflammation at Interfaces
Scientific Office, Management: Dr. habil. Susanne Holstein
Address: Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Phone: +49 431 880-4850, Fax: +49 431 880-4894
e-mail: spetermann@uv.uni-kiel.de
Twitter: I@I @medinflame

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Kiel University (CAU)
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