Antibiotics and lung sensitivity to allergens linked

Allergies making your life miserable? Tired of popping antihistamines like candy? Can't go anywhere without your inhaler? The real problem may not be your stuffed-up head. It could be the microbes in your gut.

Aspergillis fumigatus mold releasing its tiny spores. (Photo by Mairi Noverr And Gary Huffnagle, Medical School)

At the American Society for Microbiology meeting in New Orleans last month, scientists from the Medical School presented results of experiments with laboratory mice indicating that antibiotic-induced changes in microbes in the gastrointestinal tract can affect how the immune system responds to common allergens in the lungs.

"We all have a unique microbial fingerprint—a specific mix of bacteria and fungi living in our stomach and intestines," says Gary Huffnagle, associate professor of internal medicine and of microbiology and immunology. "Antibiotics knock out bacteria in the gut, allowing fungi to take over temporarily until the bacteria grow back after the antibiotics are stopped. Our research indicates that altering intestinal microflora 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 his research findings could help explain why cases of chronic inflammatory diseases, such as asthma and allergies, have been increasing rapidly during the last 40 years—a time period that corresponds with widespread use of antibiotics.

To understand the implications of the research, it's important to know something about the complex relationship between the gastrointestinal, respiratory and immune system in the human body.

Every time you inhale, air flows past mucus-producing cells and tiny hairs designed to trap bits of pollen, dust and spores before they enter the lungs. These trapped particles are swept into the stomach with saliva and mucus as you swallow.

"Anything you inhale, you also swallow," Huffnagle says. "So the immune cells in your GI tract are exposed directly to airborne allergens and particulates. This triggers a response from immune cells in the GI tract to generate regulatory T cells, which then travel through the bloodstream searching the body for these antigens. These regulatory T cells block the development of allergic T cell responses in the lungs and sinuses."

Most of the time, in ways scientists don't understand completely, the GI tract immune system modulates or dampens down the allergic T cells' response to incoming allergens in the lungs, Huffnagle says. But when antibiotics reduce the bacterial population in the GI tract, the number of yeast and other fungal organisms increases.

In an experiment, Mairi Noverr, research fellow in internal medicine, gave a five-day course of oral antibiotics to normal lab mice followed by a single oral introduction of the yeast.

"After antibiotics changed the mix of microbes in the GI tract, the mice developed an allergic response in the lungs when exposed to common mold spores," Huffnagle explains. "Mice that didn't receive the antibiotics were able to fight off the mold spores."

Complete data from the study have been submitted for publication in a future issue of Infection and Immunity.

Huffnagle emphasizes the importance of a healthy low-sugar diet, with lots of raw fruits and vegetables, after being treated with antibiotics to help restore the normal mix of microbes in your GI tract as quickly as possible.

Huffnagle's research has been funded by the National Institutes of Health and a New Investigator Award from the Burroughs-Wellcome Fund. Other collaborators include Dennis Lindell, a graduate student in immunology, and Rachel Noggle, a research assistant in internal medicine.