Protect the mucus layer of intestine to avoid trigger for Inflammatory Bowel Disease (IBD).
A Mystery Unfolding:
Chronic inflammatory bowel diseases (IBD) like Crohn’s disease and ulcerative colitis remain shrouded in mystery, leaving sufferers battling agonizing symptoms with limited treatment options.
However, a groundbreaking discovery by a research team at MedUni Vienna unveils a promising new target for potential therapies – the very surface of intestinal epithelial cells.
The Brush Border Under the Microscope:
Published in the esteemed journal EMBO Reports, the study reveals a crucial link between changes in the intestinal epithelial cell surface and the development of IBD. These cells, forming the outermost layer of the intestine, boast dense finger-like protrusions called microvilli. A protein complex known as the intermicrovillar adhesion complex (IMAC) keeps these microvilli neatly organized, resembling a well-combed head of hair.
Missing Pieces and Disappearing Order:
Prior research identified reduced levels of a specific IMAC protein (CDHR5) in IBD patients. To unravel the hidden connections, the research team used a mouse model lacking CDHR5. Electron microscopy revealed a startling sight – shortened, disorganized microvilli, akin to unkempt hair.
Beyond Appearances:
Surprisingly, this disarray alone wasn’t enough to trigger IBD or invite harmful bacteria. The crucial turning point came when the protective mucus layer above the epithelial cells was made artificially permeable.
The Perfect Storm:
“The combination of reduced IMAC protein, disorganized brush border, and a permeable mucus layer appears to be the perfect storm for triggering chronic inflammatory bowel diseases,” explains study leader Robert Eferl. This finding opens exciting possibilities for developing novel IBD therapies.
Boosting the Brush Border Defenders:
Drugs that stimulate IMAC protein production in intestinal epithelial cells could become the key to fighting IBD at its root. Additionally, the study sheds light on the link between unhealthy, high-fat diets and IBD risk. Such diets weaken the intestinal mucus layer, potentially pushing individuals predisposed to low CDHR5 production over the edge into full-blown IBD.
A Brighter Future for IBD Patients:
While further research is necessary, this groundbreaking study offers a ray of hope for millions suffering from IBD. By unveiling the intricate details of how the intestinal surface contributes to disease, it paves the way for the development of targeted therapies that address the root cause of IBD, empowering patients to reclaim their lives from the clutches of this chronic illness.
More information:
Bernadette Mödl et al, Defects in microvillus crosslinking sensitize to colitis and inflammatory bowel disease, EMBO reports (2023). DOI: 10.15252/embr.202357084