100,000€ 
investment
over 2 years

Inflammatory bowel diseases (IBDs) are the consequence of a long-term bowel inflammation, causing multiple symptoms such as abdominal pain, diarrhea or blood in the stool. Over time, the risk of evolution towards intestinal fibrosis increases (fibrous bowel, formation of scar tissue).
This evolution towards fibrosis must be specifically monitored as it may cause intestinal food bolus obstruction (bowel obstruction), necessitating surgery. In such case, the fibrosed part is removed. However, patients are at risk of recurrence and therefore face the need for multiple surgeries that will affect their quality of life.

Failure of proper gene interaction with our environment is the cause of IBDs. Millions of bacteria live in our intestine. In a healthy intestine, these bacteria are controlled and useful. With IBDs, these bacteria will activate the immune cells responsible for inflammation, intestinal wall injuries, excessive cicatrization and the formation of scar tissue. Our body can detect the presence of bacteria through a number of receptors acting as "antennas". Among these, Toll-like or Nod-like receptors are bacteria detectors that are found in significant amount in IBD patients whose response to the environment and bacteria is disrupted.

It is not known how bacteria can affect the onset of complications such as scar tissue development. The objective of this work is to demonstrate that mesenchymal cells, the main cause of scar tissue formation in the intestine, not only carry receptors for bacteria detection, but also respond to part of or all bacteria by causing fibrosis.

With this 1st grant, the Cleveland winning team will endeavor to understand precisely how mesenchymal cells detect bacteria, how they respond to their presence, and the mechanisms leading to the development of fibrosis in the intestine. This work will be performed both on human cells obtained from IBD patients and healthy individuals, and using an experimental animal model (mice) of intestinal fibrosis. This animal model, resulting from the latest technological developments, will allow to control a specific type of cells at every stages of the mouse's life, and to modify how mesenchymal cells detect the bacteria.

In addition, this work will provide information about whether and how bacteria affect the formation of scar tissue, thus opening the door for developing new therapeutic options. By altering the type of bacteria living in our intestine, we may be able in the future to control or treat the formation of fibrosis in IBD patients.