Researchers at the University of Gothenburg have made a groundbreaking discovery that could open new avenues for treating Crohn’s disease, a chronic inflammatory bowel condition. Their research focuses on repairing the gut’s protective barrier to prevent the disease from worsening.
The study, which examines tissue samples from Crohn’s disease patients and includes mouse experiments, offers fresh insight into the early mechanisms that contribute to the development of the disease. The findings, published in the Journal of Clinical Investigation Insight, suggest that reinforcing the gut’s protective barrier may prevent harmful bacteria from penetrating epithelial cells in the intestine, potentially halting the onset and progression of Crohn’s disease.
“By strengthening the gut’s protective barrier, we could prevent bacteria from breaching the epithelial cells, which could stop both the onset and progression of the disease,” said Thaher Pelaseyed, Associate Professor at the Sahlgrenska Academy, University of Gothenburg.
A Vital Defense Against Bacteria
The protective barrier of the gut is formed by a carbohydrate-rich layer called the glycocalyx, which shields the epithelial cells lining the small intestine from direct bacterial contact. A critical component of this barrier is the transmembrane mucin MUC17, which creates a dense, protective network on the surface of the epithelial cells.
The new research highlights a potential treatment strategy that goes beyond symptom management, focusing on enhancing the gut’s natural defenses to combat Crohn’s disease.
Key Discovery: Disrupted Transport Weakens Gut Barrier
The study reveals that individuals with Crohn’s disease exhibit lower levels of MUC17 on their epithelial cell surfaces, leaving the cells more susceptible to bacterial invasion. Animal studies showed that, in the absence of this protective protein, bacteria — both harmful and beneficial — were able to penetrate intestinal cells more easily, leading to cell death and inflammation.
Further investigation uncovered that the reduced MUC17 levels were not due to a lack of protein production, but rather a disruption in the protein’s transport and stability within the cells. The researchers also identified three key proteins — MYO1B, MYO5B, and SNX27 — which are essential for positioning and stabilizing MUC17 on the surface of epithelial cells. When these processes fail, the glycocalyx becomes impaired, making it easier for bacteria to invade the intestinal tissue.
Implications for Future Treatments
Pelaseyed explained that understanding the transport and stabilization of MUC17 could lead to the development of new drug targets aimed at repairing the glycocalyx barrier in Crohn’s disease. This approach could offer an alternative to traditional anti-inflammatory treatments, which often have limited effectiveness and the potential for resistance.
The research presents a novel direction for Crohn’s disease therapy, emphasizing the restoration of the gut’s natural defenses rather than solely focusing on symptom management.
With the identification of new molecular targets, this breakthrough offers hope for more effective treatments for Crohn’s disease patients in the future.
Related Topics
