According to the researchers, their unexpected findings suggest that the practice of giving antibiotics to cancer patients to prevent infections might render the gut more vulnerable to damage a danger that might be overcome by administering substances that mimic the protective presence of gut bacteria. The findings may also revise thinking about the treatment of inflammatory bowel disease (IBD), in which the intestine is believed to mount an inflammatory response to benign, or commensal, bacteria.

The researchers, led by Howard Hughes Medical Institute investigator Ruslan Medzhitov at Yale University School of Medicine, reported their studies in the July 23, 2004, issue of the journal Cell.

"Until now, almost everything we knew about the benefits of commensal bacteria had to do with their biological activity," said Medzhitov. "They metabolize nutrients to enable us to absorb them more readily. They aid in the early development of the gastrointestinal system. And they produce factors that prevent colonization by pathogenic bacteria. Our work, however, has revealed a role that is quite different."

Specifically, Medzhitov and his colleagues discovered that beneficial bacteria trigger proteins called Toll-like receptors (TLRs) to maintain the health of intestinal epithelial cells and to activate machinery that responds to injury. Previously, TLRs were thought to function strictly as assassins, recognizing molecules on the surface of pathogenic bacteria and triggering the innate immune system to attack.

"It's always been a major paradox that our immune system evolved to recognize pathogenic microorganisms and to react to them with a powerful, des
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
22-Jul-2004