Childhood asthma risk affected by bacteria in early infancy

​Children gain protection against asthma if exposed to four types of gut bacteria by the age of three months, as their immune system is being established, a team of B.C. researchers has discovered.

The researchers, from B.C. Children's Hospital, recognized asthma is the top reason for going to the hospital. It's suspected the way we're living exposes us to fewer microbes, which could contribute to the increase in asthma rates.

To explore this idea, Dr. Stuart Turvey and Prof. Brett Finlay of the University of British Columbia in Vancouver and his team studied 319 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. They used a powerful genetic technique to analyze fecal samples from the children when they were three months old.

"We're really excited about this study because we found that children at very high risk of asthma had low levels of four bacteria in their intestines," said Turvey.

Asthma is a chronic disease of the airways. It currently affects more than 300 million people worldwide and is thought to be caused by disregulation of the immune system. One in three Canadians will be diagnosed with asthma in their lifetime.

Low levels of four types of intestinal bacteria at three months were associated with children's risk of the condition, the team reports in Wednesday's issue of the journal Science Translational Medicine.

"Our ultimate goal is to look to prevent asthma in children and this is the first potential step on that journey wherein we might be able to supplement children with those bacteria. But I want to emphasize this is early days yet," Turvey said.

The four types of bacteria were Faecalibacterium, Lachnospira, Veillonella and Rothia, which the scientists nicknamed FLVR.

No one knows how the bacteria affect how a baby's immune system develops, but they have an impact in animal models, Finlay said.

Finlay said the researchers "were all blown away by how early in life" the difference occurred.

Of the children in the study, 22 were considered at very high risk of developing asthma because they showed early warning signs, such as wheezing. At three months, all of them showed low levels of the bacteria. So far, eight have been diagnosed with asthma.

To check if the missing bacteria are protective, the researchers inoculated germ-free mice with the FLVR  bacteria and found airway inflammation improved in adult offspring of the mice compared with those without the FLVR bacteria. 

The findings support the "hygiene hypothesis" of how sterilizing everything may come with a health cost in the long term.

"Maybe we've actually cleaned up things too much in our quest to get rid of all these infectious diseases," Finlay said. "I really do think we have to retool how we behave."

Early life 'crucible for healthy development'

Finlay said they aren't counselling people to shovel nasty things into the mouths of babes. But there are asthma studies suggesting if you drop a soother on the floor, for instance, it's better for the mother to put it into her own mouth and then back in the baby's mouth rather than wash it off.

"Let them crawl on the floor. Let them lick the floor. If you watch a kid in action they're basically hoovering everything they can into their mouth. Maybe there's a reason for that. Maybe they're trying to colonize themselves early in life."

Studies involving European families have shown having a pet in the house, and growing up on a farm and being exposed to bacteria in a farming environment help protect them against asthma.

"It's fine to get dirty. It's fine to play with the dog," Turvey said.

Martin Blaser and Maria Gloria Dominquez-Bello of New York University Langone Medical Center wrote a journal commentary published with the study.

"It is becoming clear that early life is indeed the crucible for healthy development," they said.

Important questions remain.

"When does the window open and when does it close? How can we recognize problems early enough to intervene? Stay tuned."

The investigators have started testing samples from 500 more Canadian babies as well as from infants in Ecuador to further explore how asthma develops. 

This research was  funded by the Canadian Institutes of Health Research.