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Gut bacteria could be key in preventing asthma in children

Four species of bacteria may play a role in protecting infants from the disease

V. Altounian / Science Translational Medicine

The bacteria in a baby's gut might play a big role in preventing an asthma diagnosis later in life, according to a study published in Science Translational Medicine today.

The guts of infants who are at high risk for asthma display low levels of four specific bacterial species when they are three months old, scientists have discovered. The finding could lead to a test that can more accurately predict which children might develop asthma, but the upshot of the study is even bigger. The scientists think their study could lead to a microbe-based treatment that might prevent the development of asthma in infants.

Asthma is a long-term lung disease characterized by inflamed and narrow airways. About 18.7 million people in the US suffer from asthma, whereas 300 million suffer from the condition worldwide. Scientists aren't sure what's causing the disease in so many people, but they think the bacteria that lives in the human gut might have something to do with it. A sample of recent studies shows that bacteria found in farm dust can trigger an immune system response in the lungs of mice that may protect them from asthma, whereas babies who are given bacteria-killing antibiotics early in life have a higher risk of developing asthma. But until now, researchers haven't been able to show that gut bacteria really do a play a role in a child's likelihood of developing asthma.

The gut microbiome seems "very important in influencing the immune responses."

"What I think is important and not so surprising to pediatricians was how important the very early life is," says Stuart Turvey, pediatric immunologist at the University of British Columbia and a co-author of the study. "And our study emphasizes that in that first 100 days the structure of the gut microbiome seems to be very important in influencing the immune responses that cause or protect us from asthma."

Scientists tested 319 infants enrolled in the Canadian Healthy Infant Longitudinal Development study to see if they were at risk of developing asthma later in life. To do that, the scientists gave them an allergy test and checked to see if the kids were wheezing. Children who displayed both symptoms were deemed most at risk for asthma. Then, the researchers analyzed stool samples taken from all 319 infants at three months of age.

The researchers found that the thee-month-olds who were most at risk for asthma — 22 in total — had much lower amounts of four specific bacterial species in their stool samples compared with kids who didn't show these symptoms. But by the time they turned a year old, the difference in gut microbe composition was much smaller. For the researchers, this result was a sign that the presence of those four microbes very early in life might have a hand in protecting kids from asthma later on.

In a second experiment, the scientists found that giving a combination of the four microbes — plus a samples of feces from one of the at-risk kids — to mice with asthma decreased inflammation in their lungs. And microbe-treated newborn mice actually developed less severe asthma than their untreated counterparts.

"This is an exciting article," says Joan Reibman, an asthma researcher at New York University. Being able to study a group of children from birth provides "invaluable information" about the presence of specific gut bacteria, and the importance of the timing of exposure to these gut bacteria.

"Five years is a short time in asthma history."

The group of children the scientists studied are now approaching age five, and are still contributing to research. Of the 22 infants who were deemed most at risk for asthma — all of which had not received antibiotics before age one — eight have been diagnosed with the lung disease. That means that even though the association appears to be a strong one, the researchers can't actually claim that these four species prevent asthma in children. For now, the association is just a link, and it's one that's only relevant for asthma risk. "Five years is a short time in asthma history," Reibman says; she wants to know what will happen as the children mature.

The results in mice hint that humans might one day have a microbe-based asthma preventative on their hands. But a lot of questions need to be answered before that can happen. For instance, the researchers don't know if a microbe-based treatment like the one used in the study will have a long-lasting effect on humans — or mice for that matter (the asthma-inducing treatment that the mice received is lethal, the researchers say). In addition, the scientists need to figure out if a microbe-based preventative can be safely administered to kids. Taken together, it's clear that any treatment that starts with this study will take a while to develop.

UBC has filed for patent protection

Still, the University of British Columbia isn't wasting any time. The institution has already filed for patent protection for this specific combination of microbes, says Brett Finlay, a microbiologist at UBC and a co-author of the study. "A company would [have to] strike a deal with UBC to license that technology and then go and develop the products" — but commercialization will "certainly take a few years." In the meantime, the findings might help scientists make a test that can determine a child's chance of developing asthma.

Overall, the study shows that the microbes that live in the human gut probably play a much bigger role in the development and regulation of the immune system than scientists thought. For Turvey, that means that pediatricians should continue to be vigilant when they prescribe antibiotics to infants. "For a virus or a cold or something else" — conditions that aren't bacterial, and therefore don't require antibiotics — "we should be much more prudent with that, because the data absolutely suggests that antibiotics and particularly multiple courses of antibiotics in the first year of life are associated with increased risk of asthma."