New gut bacteria regulate immunity

An abundant type of bacteria that resides in the intestines is critical for keeping the immune system of the colon in check, according to a study published online today (December 23) in ScienceExpress.

Clostridium perfringens
Image: Wikimedia commons, CDC

The results add to the growing body of literature that commensal microbes in the gut are key regulators of host immunity, and may provide potential therapeutic avenues for inflammatory bowel disease (IBD), allergies, and autoimmune diseases."This is a big step forward in understanding how the commensal microbiota shapes the host immune system," immunologist linkurl:Paul Forsythe;http://fhs.mcmaster.ca/medicine/respirology/faculty_member_forsythe.htm of McMaster University in Ontario, who was not involved in the study, told The Scientist in an email. "These results suggest that not only are there specific immune responses to distinct bacterial species, but that these responses are region-specific within the intestine."Over the past several years, evidence has been accumulating that the gut microbiome affects the balanced host immune system. Segmented filamentous bacteria (SFB), for example, appear to induce the production of intestinal Th17 cells, helper T cells that are critical to fighting pathogens. Too many Th17 cells, however, can promote autoimmunity without the proper balance of regulatory T cells (Tregs) to suppress the immune response against one's own cells. To see whether certain commensal bacterial species might regulate the production of Tregs in the intestines, immunologist Kenya Honda of the University of Tokyo and his colleagues compared normal mice to germ-free mice that harbored no bacteria. They found no major differences in the the small intestine, but significantly fewer Tregs in the colon, suggesting that the missing bacteria may be inducing Treg production.Antibiotic and chloroform-based tests revealed that the responsible microbes were likely spore-forming, Gram-positive bacteria. As Clostridia are one of the most abundant gut bacteria that fit this description, Honda and his colleagues colonized germ-free mice with a cocktail of 46 different strains of Clostridia. The results confirmed their suspicion -- the bacterial treatment resulted in the accumulation of Tregs in the colon. Treg levels in the small intestine did not change, however, suggesting that Clostridia only affect the production of Tregs in the lower part of the digestive tract."This is one of the first studies that identifies a specific example of a commensal microbe affecting regulatory T cells," said coauthor Ivaylo Ivanov, an immunologist at the Columbia University Medical Center in New York. There was a study published earlier this year, he noted, that suggested another bacteria, Bacteroides fragilis, could also induce Treg production in the gut, but those researchers "saw a very marginal induction of regulatory T cells," said Ivanov, who collaborated on the research while at New York University School of Medicine. "This study identifies Clostridia as a really strong inducer."If these results are representative of the human microbiome's effects on immunity, researchers might one day be able to manipulate the gut microbiota for therapeutic purposes, Forsythe added. Certain species of Clostridium are less abundant in IBD patients than healthy controls, for example, suggesting a role for the bacteria in healthy digestion. Furthermore, "your Treg response has been shown to be very important in allergy and asthma and a lot of chronic disease states, so it could be critically important that you have enough of these organisms and others to maintain this proper microbial balance, which then contributes to a proper immunological balance," said immunologist Liam O'Mahony of the Swiss Institute of Allergy and Asthma Research, who did not participate in the research."I think if we can determine how these bacteria mediate their immune effects, this may open the door to new therapeutic strategies for IBD and perhaps other disorders including allergic disease," Forsythe agreed.Indeed, at least one clinical study published in 2005 has already demonstrated a therapeutic effect of an individual microbe, O'Mahony said. Symptoms of irritable bowel syndrome improved significantly when the patients received doses of live Bifidobacterium infantis cells for eight weeks, a change accompanied by normalization of the ratios of anti-inflammatory to proinflammatory cytokines. The new study provides "tantalizing data that fits with this story," he said. "Some bugs are important for one type of immunity and other bugs are important for another type of immunity, and it's really the balance of these bugs that gives the perfect immune system."K. Atarashi, et al., "Induction of colonic regulatory T cells by indigenous Clostridium species," ScienceExpress, 10.1126/science. 1198469, 2010.
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