Sep. 11, 2000 A team of Emory University pathologists has discovered that non-pathogenic bacteria within the gastrointestinal tract may be responsible for blocking an immune pathway that otherwise could cause an unhealthy inflammatory response to the millions of bacteria normally present in the intestine. A breakdown in this mechanism for bacterial tolerance could play a fundamental role in the pathogenesis of inflammatory bowel disease (Crohn's disease and ulcerative colitis) and other infectious intestinal diseases. The research was reported in the September 1 issue of the journal Science.
The gastrointestinal tract of humans and other vertebrates is home to a delicate bacterial balancing act in which a diverse ecosystem of non-pathogenic bacteria co-exist among potential pathogens, all under the watchful guard of protective immune cells. Although the intestinal non-pathogenic bacteria, or normal flora, are known to play a biological role in enabling the breakdown of certain vitamins and other substances, scientists have generally believed these bacteria to be otherwise inert residents of the GI tract. The usually harmonious co-existence between intestinal organisms and immune cells dates back through millions of years of evolution, from the time of the earliest known vertebrates.
The Emory team of pathologists, including Andrew Neish, M.D., James Madara, M.D. and Andrew Gewirtz, Ph.D., and their colleagues, discovered that non-pathogenic bacteria in the G.I. tract are not merely the innocent intestinal wallflowers they were presumed to be, but that they actually deliver a signal that blocks an important immune-system pathway called NF-KB -- a transcription factor involved in activating genes in the immune system.
"It's fascinating that the epithelium (lining of the intestine) can tolerate the presence of this density of bacteria while also being quite permeable to nutrients and fluids," says Dr. Neish. "Almost all other tissue types in the body are exquisitely sensitive to bacteria and their products. Now we have found a mechanism by which non-pathogenic bacteria block the inflammatory pathway and prevent cells in the G.I tract from responding as any other cell would respond. This mechanism for tolerance also could be fundamental to the pathogenesis of inflammatory bowel disease (Crohn's disease and ulcerative colitis) and to other infectious intestinal diseases," he said.
Crohn's disease and ulcerative colitis are diseases in which individuals develop a chronic and debilitating intestinal inflammatory response. Inflammatory bowel disease is one of the last few major unexplained diseases, although scientists have long suspected that it is related to lack of tolerance to the community of intestinal organisms. There is a possibility that the balance of beneficial to non-beneficial bacteria is altered in these patients," explains Dr. Neish. "A genetic flaw in the epithelial lining of the G.I. tract could also cause an abnormal response to the non-pathogenic bacteria."
The discovery also may shed light on the growing field of probiotics, in which investigators are experimenting with various species of benign bacteria that can be ingested with foods, such as lacto-bacillus (found in yogurt), to improve the intestinal health of patients with inflammatory bowel disease. The Emory research could elucidate a potential mechanism for the positive effects of probiotics.
"It's interesting that the organisms we are studying are non-pathogenic and have no ability to elicit inflammation themselves, yet they are able to block inflammatory pathways and create tolerance for themselves and perhaps other organisms," said Dr. Neish. "It turns out that some non-pathogenic bacteria have a significant reciprocal ecological interaction with the host. The host can mount an immune response to control resident bacteria, but even non-pathogenic bacteria have an ability to influence that immune response."
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