Antibiotics alter GI tract microbes, increase lung sensitivity to allergens

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Sun, 9 Jan 2005 19:25:11 -0800

Antibiotics alter GI tract microbes,

increase lung sensitivity to allergens

 

 

 

 

Antibiotics alter GI tract microbes, increase lung sensitivity to

allergens

 

 

Posted on Wednesday, May 26, 2004 @ 8:20 AM PDT

Topic: Bio and Medicine

 

 

 

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 meeting held here this week,

scientists from the University of Michigan Medical School 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.

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 to

allergens

 

Study could help explain increasing rates of asthma, allergies and

inflammatory diseases

 

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 meeting held here this week,

scientists from the University of Michigan Medical School 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 and allergies, 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.

 

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.''

 

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.