Mr Edwin Charles Clark

Title: Cellular and molecular mechanisms of nutritional modulation of intestinal barrier function

Project Start Date: 1 November 2000

Completion Date: October 2002

Summary:

All human beings carry vast numbers of bacteria within their gut. Under normal circumstances these cause no problems and may even be beneficial to health. However when people become seriously ill these bacteria can leak out of the gut and cause life threatening infection. Many of these seriously ill patients lack vital nutrients, as these can be difficult to provide. Lack of specific nutrients is known to be a factor in the passage of bacteria out of the gut and into the body, though little is known about the specific mechanisms of how this happens.

The long-term aim of my project is that by understanding some of the mechanisms surrounding the escape of bacteria, we might provide better nutrition for seriously ill patients and reduce infectious complications.

I will model the lining of the gut, using cells grown in culture. I have already shown that, starving these cells for short periods of vital nutrients renders them very vulnerable to damage from chemicals, produced by the body during serious illness, that cause inflammation. This damage makes the cells leaky and allows bacteria to pass through, which they would not do under normal circumstances. It is not known whether the nutrients or their metabolites are important in this process. I plan to investigate the mechanisms involved in bacteria escaping from the gut and to focus on which particular nutrients or metabolites are most important in this process.