An inner mucus layer prevents bacteria from causing inflammation in the large intestine

In the absence of the molecule that builds these two mucus layers allows the bacteria can reach the epithelial cells, cause inflammation and later on colon cancer as shown by research at the Sahlgrenska Academy at University of Gothenburg in collaboration with Uppsala University and Albert Einstein, New York.

All human beings have more than two pounds of bacteria in their large intestine and the number of bacteria outnumbers the total number of cells in the body by a factor of 10. How we can live with all these bacteria without deleterious effects or diseases have not been understood until now.

A couple of years ago, the research group of Lena Holm at Uppsala University could show that that there were two mucus layers in the colon that together gave a millimeter thick mucus layer.

– We understood already at that time that this must be important for protecting the large intestine, but we could not guess that the inner layer was such a good barrier for bacteria, says Professor Lena Holm at Uppsala University that has taken part in the current research.

In the article it is shown that both mucus layers have an identical composition where an enormous mucin protein called Muc2 is the main constituent. This is a protein that the Gothenburg group has been working on for more than 10 years to understand its function. The Muc2 mucin and other components is formed in the goblet cells where the inner mucus layer is attached. This layer is continuously renewed from below and after a tenth of a millimeter it is released and expanded in volume at least four times. This outer layer can then be transported away together with the intestinal content.

When the authors studied were all the intestinal bacteria were located, it was observed that the inner mucus layer was devoid of bacteria and that all bacteria were in the outer layer.

– It was really fascinating to find that the inner mucus layer lacked bacteria and that it was such a sharp border between the inner and outer mucus layers, says Ph.D. student Malin Johansson that has done most of the studies.

The mucus layer of colon build by the Muc2 mucin is a dense network that makes a physical obstacle for the bacteria to penetrate down through the mucus to reach the intestinal cells. When this mucus layer expands in volume in the outer layer it becomes a thriving milieu for the intestinal bacteria that also feed on the Muc2 mucin.

When the research group studied what happens in mice that lack the Muc2 mucin, the bacteria were not only found to be in direct contact with the intestinal cells, but could also penetrate down into the crypts and into the intestinal epithelial cells. These animals got an inflammation and later on colon cancer, a scenario that is similar to the human disease ulcerative colitis.

– Ulcerative colitis is a serious disease, but researchers have still not understood the cause of this disease. We believe that the solution to this puzzle is to be found in defects in the mucus layer that protects the large intestine, says Professor Gunnar C. Hansson that has directed the current research.

Journal: Proceedings of the National Academy of Sciences USA
Title: The inner of the two Muc2 mucin dependent mucus layers in colon is devoid of bacteria

Authors: Malin E.V. Johansson, Mia Phillipson, Joel Petterson, Anna Velcich, Lena Holm, and Gunnar C. Hansson

For more information, please contact:
Professor Gunnar C. Hansson, Dept. Medical Biochemistry, University of Gothenburg, tel: +46-31-773 3488, email: gunnar.hansson@medkem.gu.se

Ph. D. student Malin Johansson, Dept. Medical Biochemistry, University of Gothenburg, tel: +46-31-773 3070, email: malin.johansson@medkem.gu.se

Professor Lena Holm, Dept. Medical cellbiology, Uppsala University, tel: +46-18-471 43 25, email: lena.holm@mcb.uu.se