Lay Summary

Proposal No.   IBD-0040R
Principal Investigator:  Subrata Ghosh, M.D.
Applicant Organization:  Imperial College School of Science, Technology and Medicine (London, United Kingdom)
Project Title: Do dietary microparticles modulate macrophage activation and phagocytosis in Crohn's disease?
Period of Award:  September 1, 2003 - April 30, 2005

Increase in the incidence of Crohn’s disease in certain populations, especially children, suggests environmental factors that initiate or perpetuate gut inflammation in genetically susceptible individuals.  Microparticles (i.e., microscopic grit) of aluminium, titanium, chromium and silicon have been demonstrated within the gut lining in patients with Crohn’s disease.  These particles, which are mostly food additives in the modern diet, are absorbed into key immune cells called macrophages.  Macrophages play an important role in the inflammation characterising Crohn’s disease, and can both kindle inflammation and, in some situations, play a part in extinguishing it.  Based on some previous findings, we propose that microparticles interfere with the ability to extinguish inflammation in individuals susceptible to Crohn’s disease.
 
Western diets contain enormous amounts of microparticles, mostly in processed food. Microparticle–free diets have been shown to benefit some patients with Crohn’s disease, but it is not clear how microparticles might affect macrophage function.  Understanding this aspect will not only give biological plausibility to the hypothesis that microparticles may initiate or perpetuate gut inflammation, but also open up avenues to prevent amplification of gut inflammation.  We propose to investigate how microparticles might affect macrophage function in Crohn’s disease, and whether this might influence inflammatory activity.