Antibiotics alter microbes in GI tract and increase lung sensitivity to allergen

[Guest guest]

Antibiotics alter microbes in GI tract and increase lung sensitivity to

allergens, say U-M scientists

Study could help explain increasing rates of asthma, allergies and

inflammatory diseases

NEW ORLEANS – 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.

At the _American Society for Microbiology_ (http://www.asm.org/) meeting

held here this week, scientists from the _University of Michigan Medical

School_ (http://www.med.umich.edu/medschool) will present 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 B. Huffnagle,

Ph.D.,

an associate professor of internal medicine and of microbiology and

immunology in the U-M Medical School . “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.â€

If confirmed in human clinical studies, Huffnagle believes his research

findings could help explain why cases of chronic inflammatory diseases, like

_asthma_ (http://www.med.umich.edu/1libr/aha/umastfacts.htm) and _allergies_

(http://www.med.umich.edu/1libr/aha/umalerg03.htm) , have been increasing

rapidly

over the last 40 years – a time period that corresponds with widespread use

of antibiotics.

To understand the implications of the U-M 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.â€

Most of the time, in ways scientists don't completely understand, the GI

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 that fungi

secrete molecules called oxylipins, which can control the type and intensity of

immune responses. Huffnagle says this suggests the intriguing possibility

that fungal oxylipins in the GI tract prevent the development of regulatory T

cells for swallowed allergens. In the absence of regulatory T cells from the

GI tract, T cells in the lungs become sensitized to the presence of ordinary

mold spores, pollen or other allergens. The result is a hyperactive immune

response, which can produce allergy symptoms or even asthma.

To test Huffnagle's hypothesis, Mairi C. Noverr, Ph.D., a U-M 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, Candida

albicans, to create a consistent, reproducible colony of microbes in the

stomach and

intestines. C. albicans is normally found in the GI tract, and increased

growth of C. albicans in the gut is a common side-effect of antibiotics.

An

allergic response in the airways of a mouse. The dark staining is excess

mucus being secreted into the airways - a result of the underlying allergic

inflammation.

Two days after stopping the antibiotics – at a time when the gut bacteria

were growing back - Noverr exposed the mice to a common mold allergen called

Aspergillus fumigatus by inoculating spores into the nasal cavities of all the

mice in her study. She then examined the mice for the presence of an allergic

response in the airways and compared results between the mice that received

antibiotics and those that did not.

“Mice treated with antibiotics and colonized with C. albicans showed

increased pulmonary hypersensitivity to A. fumigatus compared with mice that

didn't

receive antibiotics,†Noverr says. “The inflammatory response grew stronger

with every exposure to the allergen.â€

“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,â€

Huffnagle explains. “Mice that didn't receive the antibiotics were able to

fight off the mold spores.â€

Huffnagle and Noverr will discuss details of the experiment in a symposia

lecture and poster presentation at the ASM meeting. Complete data from the

study has been submitted for publication in a future issue of _Infection and

Immunity_ (http://iai.asm.org/) .

Huffnagle maintains that disruptions in the growth of bacteria and fungi in

the GI tract somehow interfere with the ability of regulatory T cells to

dampen the immune response to respiratory allergens. In future research, he

hopes

to determine exactly how gastrointestinal microbes are involved in the

process of immune system modulation.

“We know from laboratory experiments that dietary antioxidants called

polyphenols, which are found in fruits and vegetables, can limit fungal growth

and

that a diet high in saturated fats and sugars slows the recovery of normal

gut microflora,†Huffnagle adds. “The Mediterranean diet is rich in sources

of

polyphenols, so it's intriguing that Mediterranean-diet countries have lower

rates of allergies, asthma and other inflammatory diseases than Western-diet

countries like the United States , Canada and England .

“If we can determine exactly how microflora in the GI tract affect the

immune system, it may be possible one day to prevent or treat allergies and

inflammatory diseases with diet changes or probiotics – dietary supplements

of ‘

healthy' bacteria designed to restore the normal balance of microbes in the

gut,

†Huffnagle adds. “In the medical community, probiotic therapy is becoming

an area of increasing interest.â€

Until then, 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. “The old saying, ‘an apple a day keeps the doctor away' may be

more

true than we thought,†he says.

Huffnagle's research has been funded by the National Institutes of Health

and a New Investigator Award from the Burroughs-Wellcome Fund. Other

collaborators in the research include Dennis M. Lindell, a U-M graduate student

in

immunology, and Noggle, a research assistant in internal medicine.

Note This is a basic scientific research study conducted in laboratory mice.

Much additional research will be required before scientists will know if

these results can be applied directly to people. Your physician is the best

source of advice for questions about antibiotics and treatment of asthma,

allergies and other inflammatory diseases.

Contact: Sally Pobojewski