> tryin again Mike [you are so kind and patient]. it should be RTF and if
> there is an hmtl too, I dont see how. davido

Thanks Davido. In case anybody is uncomfortable with opening the rtf 
formatted file, here it is in plain text...

Mike D.

>>>>>begin included message

I think the following is very interesting, particularly seein's we were 
recently talking about it here. 

davido 

Healthy Mix of GI Tract Microbes Are Key to Preventing Allergies, 
Asthma Libraries Medical News 

Keywords ALLERGIES ASTHMA ANTIBIOTICS GASTROINTESTINAL MICROFLORA 
Contact Information 

If you want to avoid allergies or asthma, scientists at the University 
of Michigan Medical School suggest you start paying more attention to 
what's in your gut. 

Editors: Color images of C. albicans and inflammatory cells from the 
lungs of mice in the U-M study are available on request. 

Newswise - If you want to avoid allergies or asthma, scientists at the 
University of Michigan Medical School suggest you start paying more 
attention to what's in your gut. 

In the January 2005 issue of Infection & Immunity, U-M researchers 
report new evidence suggesting that changes in the normal mixture of 
microflora - bacteria and fungi in the gastrointestinal tract - can 
intensify the immune system's reaction to common allergens, like pollen 
or animal dander, in the lung and increase the risk of developing 
chronic allergies or asthma. 

"Our research indicates that microflora lining the walls of the 
gastrointestinal tract are a major underlying factor responsible for 
the immune system's ability to ignore inhaled allergens," says Gary 
Huffnagle, Ph.D., an associate professor of internal medicine and of 
microbiology and immunology in the U-M Medical School. "Change the 
microflora in the gut and you upset the immune system's balance between 
tolerance and sensitization." 

To test their hypothesis, Huffnagle and Mairi C. Noverr, Ph.D., a U-M 
post-doctoral fellow, have developed the first mouse model designed to 
mimic how humans develop allergies following antibiotic therapy. In a 
just-published study in the current issue of Infection & Immunity, they 
report results of new experiments linking changes in GI tract 
microflora to an overzealous allergic response in the lung. 

Instead of sensitizing them to an allergen in advance, Noverr gave 
normal Balb/C laboratory mice a five-day course of antibiotics, which 
killed their gut bacteria, followed by a single oral introduction of 
the yeast Candida albicans. Increased growth of C. albicans in the gut 
is a common side-effect of antibiotics. 

After stopping the antibiotics, Noverr inserted ovalbumin - a commonly 
used experimental allergen derived from egg whites - via the nasal 
cavities of all the mice in the study. Then, she examined the mice for 
the presence of an allergic response in the airways and compared 
results between mice that received antibiotics and those that did not. 

"The antibiotic-treated mice showed increased airway hypersensitivity 
to ovalbumin compared to mice that didn't receive antibiotics," Noverr 
says. "These results confirm our previous experiments, in which we used 
a genetically different strain of laboratory mice [C57BL/6] and a 
different type of allergen - mold spores, instead of ovalbumin." 

Results of Huffnagle and Noverr's previous work were published in the 
August, 2004 issue of Infection & Immunity. It was the first study 
linking changes in GI tract microflora to an allergic response in the 
lung. 

"In our new study, we found that differences in host genetics and the 
type of allergen used didn't matter. The immune responses were 
literally identical," Huffnagle says. "It confirms our earlier findings 
that gut microflora are the key to maintaining a balanced immune 
response, that changing the composition of microflora in the gut 
predisposes animals to allergic airway disease, and that allergic 
sensitization can occur outside the lungs." 

Noverr and Huffnagle suspect that changes in gut microflora caused by 
widespread use of antibiotics and a modern high-fat, high-sugar, low-
fiber diet could be responsible for a major increase, over the last 40 
years, in cases of chronic asthma and allergies in Western 
industrialized countries. 

"The recent increase in allergies and asthma has been attributed to 
what's called the 'hygiene hypothesis,' the idea that children in 
Western countries are not exposed to enough infections early in life to 
prevent the immune system from reacting to harmless antigens," Noverr 
explains. "We're coming at it from a different angle. Our emphasis is 
on what's going on in the GI tract." 

The link between lung and gut may not seem obvious at first. But 
Huffnagle points out that every time we swallow, particles of dust, 
pollen and spores - trapped by mucus-producing cells and tiny hairs 
lining the respiratory tract - are washed into the stomach where they 
come in direct contact with immune cells in the GI tract. 

"Think of the body as a big tube with everything from nose to rear end 
exposed to allergens from the outside world," Huffnagle says. "The 
immune system's normal response to all this stuff we constantly inhale 
is to actively ignore it - a reaction we call tolerance. The key to 
tolerance is an immune cell called a regulatory T cell." 

Discovered just a few years ago, regulatory T cells are under intense 
research scrutiny, because of their ability to moderate or cool down 
the immune response. 

"If lungs are repeatedly exposed to an allergen, regulatory T cells 
learn to recognize the allergen as not dangerous and something that can 
be safely ignored," Huffnagle says. "Most researchers think that 
tolerance develops in the lungs, but we believe it actually occurs in 
the gut. When immune cells in the GI tract come in contact with 
swallowed allergens, that interaction triggers the development of 
regulatory T cells, which then migrate to the lungs." 

Everyone has a personal microbial fingerprint - a unique mix of 
bacteria and fungi living in the stomach and intestines - which 
develops in the first years of life. As long as the balance of gut 
microflora remains stable, tolerance continues. But anything that 
alters this intestinal balance - taking antibiotics, switching from 
breast milk to formula, eating a high-sugar, low-fat diet - interferes 
with the system and can lead to problems. 

"One short course of antibiotics is not going to give everyone 
allergies," Huffnagle says. "But if you are taking antibiotics while 
your diet consists of white bread and fried food, you are not going to 
maintain the healthy microflora balance you need to maintain tolerance. 
If you inhale mold spores or pollen during this period, our studies 
indicate you are much more likely to become sensitized to them." In 
future research, Huffnagle hopes to learn whether changing only the 
diet of his experimental mice will alter gut microflora and change the 
immune response to allergens in the same way as antibiotics. Noverr 
plans to focus on identifying the microbial compounds that activate the 
immune response and learning how bacterial dietary supplements called 
probiotics can affect this microbial balance in a positive way. 

"We are not advocating that people stop using antibiotics when they are 
medically necessary," Huffnagle cautions. "But we are advocating that 
people understand the importance of eating a healthy diet, with lots of 
fruits and vegetables, after taking antibiotics to help restore the 
normal mix of GI microflora as quickly as possible." 

Noverr and Huffnagle's research is funded by the National Institutes of 
Health and a New Investigator Award from the Burroughs-Wellcome Fund. 
Other U-M collaborators in the study were Nicole R. Falkowski and Rod 
A. McDonald, research associates, and Andrew N. McKenzie of the Medical 
Research Council Laboratory of Molecular Biology in Cambridge, UK. 



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