Immune Defect Makes Gut Bacteria Turn Bad

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The findings emphasize the importance of the interplay among the gut, its microbes, and its immune squad. The model opens new avenues to study inflammatory bowel disease and to test potential new therapies for people, said senior author Laurie Glimcher, the Irene Heinz Given professor of immunology at HSPH, and her colleagues. The study appears in the Oct. 5 Cell.

"To my knowledge, this is the first paper to show that a host immune defect can shape the composition of microflora in a way that results in pathology," said Lora Hooper, assistant professor of immunology and microbiology at the University of Texas Southwestern Medical Center in Dallas.

"That's interesting in and of itself, but they went one step further and induced this inflammation in healthy mice by transferring the microflora," said Hooper, who was not involved in the study. "The implications of that are profound."

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The researchers did not identify a specific disease-causing bacterial species, said lead author Wendy Garrett, a postdoctoral fellow in the Glimcher lab. They ruled out known troublemakers, such as Helicobacter pylori, Salmonella, and E. coli. Antibiotic experiments narrowed the probable menace down to an anaerobic species. Hooper speculates that a complex change in the community of bacteria likely unleashes renegade behavior among several species. The Glimcher lab is trying to unmask the culprits in collaboration with Jeff Gordon at Washington University in St. Louis, whose group may be best known for finding evidence that intestinal bacterial composition may contribute to obesity.

Except for isolated reports, there is little evidence that inflammatory bowel disease is contagious among people, said Richard Blumberg, chief of gastroenterology at Brigham and Women's Hospital. In the study, the maleficent microbial mix may have passed from mother to pup during birth and by feces-eating habits of unrelated mice.

No one knows exactly what causes inflammatory bowel disease. There is no cure, only treatment for symptoms, such as relieving the inflammation, and supportive therapies, such as nutrition, said Wayne Lencer, chief of gastroenterology at Children's Hospital Boston. Antibiotics may work in some patients for one major type--Crohn's disease--but not for the other--ulcerative colitis.

"We have pretty good genetic evidence that it's an abnormality of the immune system at one level and that the disease is due to a dysregulated immune response within mucosal tissues to bacteria normally resident in the intestines," said Blumberg, HMS professor of medicine. But the primary cause--immune system or bacteria--is debated, he said. This study knits together the two concepts.

"What's amazing here is that the microbe appears to be coming from the normal commensal bacteria population," said Lencer, HMS associate professor of pediatrics. "We live symbiotically with microbes. They're essential. We typically don't think of commensals as invasive. The study really makes poignant how important this dialogue is between commensals and our cells."

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