Antibiotics alter GI tract microbes, increase lung sensitivity to allergens

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Antibiotics alter GI tract microbes, increase lung sensitivity toallergensPosted on Wednesday, May 26, 2004 @ 8:20 AM PDTTopic: Bio and MedicineAllergies making your life miserable? Tired of popping antihistamineslike candy? Can't go anywhere without your inhaler? The real problemmay not be your stuffed-up head. It could be the microbes in your gut.At the American Society for Microbiology meeting held here this week,scientists from the University of Michigan Medical School will presentresults of experiments with laboratory mice indicating thatantibiotic-induced changes in microbes in the gastrointestinal tractcan affect how the immune system responds to common allergens in thelungs.http://www.scienceblog.com/community/modules.php?name=News & file=article & sid=2774 From the University of Michigan Health System :Antibiotics alter GI tract microbes and increase lung sensitivity toallergensStudy could help explain increasing rates of asthma, allergies andinflammatory diseasesAllergies making your life miserable? Tired of popping antihistamineslike candy? Can't go anywhere without your inhaler? The real problemmay not be your stuffed-up head. It could be the microbes in your gut.At the American Society for Microbiology meeting held here this week,scientists from the University of Michigan Medical School will presentresults of experiments with laboratory mice indicating thatantibiotic-induced changes in microbes in the gastrointestinal tractcan affect how the immune system responds to common allergens in thelungs.''We all have a unique microbial fingerprint – a specific mix ofbacteria and fungi living in our stomach and intestines,'' says GaryB. Huffnagle, Ph.D., an associate professor of internal medicine andof microbiology and immunology in the U-M Medical School.''Antibiotics knock out bacteria in the gut, allowing fungi to takeover temporarily until the bacteria grow back after the antibioticsare stopped. Our research indicates that altering intestinalmicroflora this way can lead to changes in the entire immune system,which may produce symptoms elsewhere in the body.''If confirmed in human clinical studies, Huffnagle believes hisresearch findings could help explain why cases of chronic inflammatorydiseases, like asthma and allergies, have been increasing rapidly overthe last 40 years – a time period that corresponds with widespread useof antibiotics.To understand the implications of the U-M research, it's important toknow something about the complex relationship between thegastrointestinal, respiratory and immune system in the human body.Every time you inhale, air flows past mucus-producing cells and tinyhairs designed to trap bits of pollen, dust and spores before theyenter the lungs. These trapped particles are swept into the stomachwith saliva and mucus as you swallow.''Anything you inhale, you also swallow,'' Huffnagle says. ''So theimmune cells in your GI tract are exposed directly to airborneallergens and particulates. This triggers a response from immune cellsin the GI tract to generate regulatory T cells, which then travelthrough the bloodstream searching the body for these antigens. Theseregulatory T cells block the development of allergic T cell responsesin the lungs and sinuses.''Most of the time, in ways scientists don't completely understand, theGI tract immune system modulates or dampens down the allergic T cells'response to incoming allergens in the lungs, according to Huffnagle.But when antibiotics reduce the bacterial population in the GI tract,the number of yeast and other fungal organisms increases.In previous studies, researchers in Huffnagle's lab discovered thatfungi secrete molecules called oxylipins, which can control the typeand intensity of immune responses. Huffnagle says this suggests theintriguing possibility that fungal oxylipins in the GI tract preventthe development of regulatory T cells for swallowed allergens. In theabsence of regulatory T cells from the GI tract, T cells in the lungsbecome sensitized to the presence of ordinary mold spores, pollen orother allergens. The result is a hyperactive immune response, whichcan produce allergy symptoms or even asthma.To test Huffnagle's hypothesis, Mairi C. Noverr, Ph.D., a U-M researchfellow in internal medicine, gave a five-day course of oralantibiotics to normal lab mice followed by a single oral introductionof the yeast, Candida albicans, to create a consistent, reproduciblecolony of microbes in the stomach and intestines. C. albicans isnormally found in the GI tract, and increased growth of C. albicans inthe gut is a common side-effect of antibiotics.Two days after stopping the antibiotics – at a time when the gutbacteria were growing back - Noverr exposed the mice to a common moldallergen called Aspergillus fumigatus by inoculating spores into thenasal cavities of all the mice in her study. She then examined themice for the presence of an allergic response in the airways andcompared results between the mice that received antibiotics and thosethat did not.''Mice treated with antibiotics and colonized with C. albicans showedincreased pulmonary hypersensitivity to A. fumigatus compared withmice that didn't receive antibiotics,'' Noverr says. ''Theinflammatory response grew stronger with every exposure to the allergen.''''After antibiotics changed the mix of microbes in the GI tract, themice developed an allergic response in the lungs when exposed tocommon mold spores,'' Huffnagle explains. ''Mice that didn't receivethe antibiotics were able to fight off the mold spores.''Huffnagle and Noverr will discuss details of the experiment in asymposia lecture and poster presentation at the ASM meeting. Completedata from the study has been submitted for publication in a futureissue of Infection and Immunity.Huffnagle maintains that disruptions in the growth of bacteria andfungi in the GI tract somehow interfere with the ability of regulatoryT cells to dampen the immune response to respiratory allergens. Infuture research, he hopes to determine exactly how gastrointestinalmicrobes are involved in the process of immune system modulation.''We know from laboratory experiments that dietary antioxidants calledpolyphenols, which are found in fruits and vegetables, can limitfungal growth and that a diet high in saturated fats and sugars slowsthe recovery of normal gut microflora,'' Huffnagle adds. ''TheMediterranean diet is rich in sources of polyphenols, so it'sintriguing that Mediterranean-diet countries have lower rates ofallergies, asthma and other inflammatory diseases than Western-dietcountries like the United States, Canada and England.''If we can determine exactly how microflora in the GI tract affectthe immune system, it may be possible one day to prevent or treatallergies and inflammatory diseases with diet changes or probiotics –dietary supplements of 'healthy' bacteria designed to restore thenormal balance of microbes in the gut,'' Huffnagle adds. ''In themedical community, probiotic therapy is becoming an area of increasinginterest.''Until then, Huffnagle emphasizes the importance of a healthy low-sugardiet, with lots of raw fruits and vegetables, after being treated withantibiotics to help restore the normal mix of microbes in your GItract as quickly as possible. ''The old saying, 'an apple a day keepsthe doctor away' may be more true than we thought,'' he says.Huffnagle's research has been funded by the National Institutes ofHealth and a New Investigator Award from the Burroughs-Wellcome Fund.Other collaborators in the research include Dennis M. Lindell, a U-Mgraduate student in immunology, and Rachel Noggle, a researchassistant in internal medicine.