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

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Antibiotics alter microbes in GI tract and increase lung sensitivity to

allergens, say U-M scientists

_http://www.med.umich.edu/opm/newspage/2004/allergies.htm_

(http://www.med.umich.edu/opm/newspage/2004/allergies.htm)

 

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.

 

 

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 Gary 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.**

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.**

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.

 

 

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.**

**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.**

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 .**

**f 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.**

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 Rachel 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