Lay Summary

Proposal No.   IBD-0098
Principal Investigator:  James Anderson, M.D., Ph.D.
Applicant Organization:   University of North Carolina at Chapel Hill (U.S.A.)
Project Title:  The role of intestinal flora in transcriptional and functional control of the tight junction barrier
Period of Award:  January 1, 2004 – February 28, 2005

The inner surface of the bowel creates a barrier to entry into the body of potentially harmful intestinal contents.  The first line of defense is formed sheets of cells and a specialized intercellular barrier between them called the “tight junction.”  While we are highly dependent on the normal resident bacteria for proper digestion, inflammatory bowel disease results from an abnormal immune response to these normal bacteria.

One hypothetical reason for this inappropriate response is that the barrier lining of the bowel becomes leaky and allows proinflammatory bacterial products to enter the body.  It was recently shown that bacteria can induce changes in gene expression of the bowel and this is a normal symbiotic response.  In addition, so-called “probiotic” species of bacteria have proven used in treating some aspects of human IBD and can protect genetically colitis-prone mice from colitis that is induced by colonization with normal bacteria.

Our studies will address whether bacteria can regulate the genes encoding tight junction proteins and barrier tightness and whether probiotic species can induce a tighter barrier as part of their ability to protect from colitis.  We will study mice with defined intestinal bacteria available from the University of North Carolina Gnotobiotic Rodent Core.  We predict the germ-free gut will have a leaky barrier and that normal bacteria and probiota will induce a tighter barrier.  Understanding the role of bacteria in controlling the barrier will provide insight into the therapeutic mechanism of probiotic bacteria in IBD and whether there exist a connection between a leaky barrier and inflammation.