New protein discovery gives hope to bowel disease sufferers
intestinal against microbial invaders offering new insights into
how the intestine fends off pathogens and potentially leading to
new inflammatory bowel disease medications.
According to Espicom business intelligence, by 2010 total prevalence of inflammatory bowel disease will increase by approximately 221,000 worldwide, 137,000 with ulcerative colitis and 74,000 with Crohn's disease. This will bring the total number to 2.2m identified cases worldwide.
Researchers at UT Southwestern Medical Center used mice raised inside sterile plastic bubbles. Because they are never in contact with the outer, microbe-filled world, these mice do not have the bacteria that normally colonise the gut.
By exposing these "germ-free" mice to different types of gut bacteria, the researchers were able to observe how the epithelial cells lining the intestine react to microbial invaders.
"We found that when the gut lining comes into contact with bacteria, it produces a protein that binds to sugars that are part of the bacterial outer surfaces," said Lora Hooper, assistant professor of immunology and the paper's senior author.
"Once bound, these proteins quickly destroy their bacterial targets."
Microbial cells in the human gut outnumber the body's own cells by about 10 to 1. Humans offer a safe haven to these microbes because they help us to break down food that we can't digest by ourselves.
But it hasn't been clear how we keep these microscopic gut dwellers from invading our tissues and causing infections.
The protein, called RegIIIgamma in mice and HIP/PAP in humans, belongs to a protein class called lectins, which bind to sugar molecules. These particular lectins' seek-and-destroy mission may help to create an "electric fence" that shields the intestinal surface from invading bacteria.
Crohn's disease and ulcerative colitis are inflammatory disorders affecting the gastrointestinal tract, and are collectively known as inflammatory bowel disease.
Currently, the management of IBD has relied on NSAI drugs such as 5-aminosalicylates (5-ASAs), glucocorticoids, and antibiotics.
These therapies are limited by a slow onset of action, incomplete response rate and significant risk of adverse effects.
In addition to these compounds immunoregulatory agents used in IBD were expanded to include methotrexate and cyclosporine in select patient populations
The study, published today in the journal Science, commented that the findings of this study could offer researchers new clues about the causes of inflammatory bowel disease.
The study may also help scientists devise more effective treatments for intestinal infections.
"We are now working to understand the mechanism by which the intestinal lining senses bacterial threats. What turns this protein antibiotic on?"
"We want to explore whether this is something we can stimulate artificially to stave off pathogenic infections," Hooper commented.
