Researchers publish the first computational insights into colonic motility to advance understanding of ulcerative colitis

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes inflammation and sores (ulcers) in the digestive tract. Ulcerative colitis affects the inner lining of the large intestine, also called the colon and rectum. At least 40,000 people live with IBD in Ireland, and more than 5 million worldwide.

Recently in a new article published in Computers in biology and medicineresearchers from CÚRAM at the University of Galway and collaborators from the University of Birmingham present a new computer model that simulates the shear stress distribution in the colon with varying mucus thicknesses.

The colon, an essential part of our digestive system, relies on rhythmic contractions to move waste. These movements create mechanical forces on the mucus-lined surface of the colon. This mucus acts as a protective barrier, separating the inside of our bodies from the trillions of microbes in our intestines.

The research team’s computer model uses real-world data about these movements, mucus behavior and tissue characteristics to simulate the dynamic environment. Their research shows how the mucus layer acts as a lubricant, significantly increasing fecal velocity and facilitating waste movement through the colon. This effect is reduced in UC, where the mucus layer is thinner, potentially contributing to constipation.

The model emphasizes the protective function of mucus and protects the thin cell layer that carries out the colonic processes against mechanical forces.

When the research team, led by Dr. Yury Rochev, School of Physics, University of Galway, examined the mechanical distribution in the cell layer, they found that shear stress varies along the different functional zones, suggesting a possible role in regulating cell migration. differentiation and immune responses. However, when this protection is compromised, as in UC, it can contribute to inflammation and tissue damage.

Dr. Rochev said: “Our model shows that mucus acts as a lubricant, significantly increasing fecal velocity and facilitating waste movement through the colon. This effect is reduced in ulcerative colitis (UC), where the mucus layer becomes thinner, potentially contributing of constipation.”

The model’s revelations don’t stop there. It also emphasizes the protective function of mucus, protecting the delicate cells responsible for essential intestinal processes from the mechanical forces generated by bowel movements.

Dr. Rochev added: “When we examined the mechanical distribution in the cell layer, we found that shear stress varies along the different functional zones, suggesting a possible role in regulating cell migration, differentiation and immune responses. When this protection is compromised, as with UC, it could contribute to inflammation and tissue damage.”

The team does not rely solely on computer simulations. They are developing an experimental model using organ-on-a-chip technology to validate their findings.

Ibrahim Erbay, a researcher on the team, said: “We use intestinal organoids to create a replica of the thin cell layer on the surface of the colon. By actively flowing fluid with the organ-on-a-chip platform, we can experience mechanical forces similar to those in the colon.”

By combining computational modeling with robust experimental validation, the researchers aim to gain a comprehensive understanding of how mechanical forces influence biological events in both health and disease. This holistic approach promises to improve our understanding of gut health and pave the way for new, targeted therapies for inflammatory bowel disease and other digestive disorders.

Researcher Erbay added: “This study not only advances our understanding of the fundamental function of the colon at the cellular level, but also provides a powerful tool for developing new therapeutic approaches. We can now model different drug delivery systems and optimization, which could potentially lead to more effective therapies.” treatments for gut-related conditions.”