Could asthma start with your gut?

How our gut bugs can influence our health

April 8, 2016

It's a puzzle: Asthma rates are skyrocketing in developed countries, but not elsewhere.

In Canada, the number of children diagnosed with asthma has quadrupled in the past 20 years. It's the leading cause of pediatric hospitalizations, resulting in 275,000 emergency room visits each year, and it's the top reason for physician billing for children in Canada. But it isn't just children: nearly three million Canadians—or 8.3% of the general population aged 12 and over—are affected.

Although the exact cause of asthma is unknown, new research is uncovering the ways in which this disease of the lungs could actually be linked to the bacteria living in our guts.

There is growing evidence that microbiota—the community of microorganisms, including bacteria, that live on, in and around us—have an impact on our health. More specifically, research is starting to show us that microbiota can affect the development of our immune systems. Asthma is actually an inflammatory immune response in the lungs, so the link between microbiota and the ways in which they shape our immune system is an important area of investigation.

Nearly eight years ago, the link between microbiota and asthma piqued the interest of Dr. Brett Finlay, an award-winning microbiologist who is the Peter Wall Distinguished Professor in the Michael Smith Laboratories and in the Departments of Biochemistry and Molecular Biology and Microbiology and Immunology at the University of British Columbia. In his lab, he and his team were using antibiotics to change microbiota in mice. "I was telling my wife Jane, who is a paediatrician, [about the experiments] and she mentioned that kids who got antibiotics in the first year of life had higher asthma rates," he explains. "So I looked it up, and of course she was right."

Dr. Brett Finlay
Photo courtesy of Carlos Taylhardat, Art of Headshots.

Studies have indicated a link between antibiotic use and an increased risk of developing asthma. One study, led by Dr. Anita Kozyrskyj from the University of Alberta, showed that children receiving more than four courses of antibiotics in the first year of life have 1.5 times the risk of asthma compared with children not receiving antibiotics. This change in asthma risk intrigued Dr. Finlay, who notes that there were other "smoking guns" that pointed to microbiota as contributors to the development of asthma—but not in the way that most of us might expect. Having a pet or living on a farm was associated with a decreased risk of developing asthma, for example, as were vaginal delivery and breastfeeding. The more exposure to beneficial "bugs", it seemed, the lower the risk of developing asthma. But more research was needed to be sure.

Intent to uncover the link between intestinal microbiota ("gut bugs") and the development of asthma, Dr. Finlay and his team spent the next few years conducting a number of studies using mice. Intriguingly, their work showed that antibiotics that affect gut bugs do have a drastic impact on asthma rates and, in fact, it also showed that certain sets of gut bugs may have a protective or worsening effect on asthma. But there was a catch: the asthma rates and severity were only affected if the gut bugs were altered very early in the mouse's life—before weaning.

It was time to see if the same effect could be observed in humans. With funding from a Canadian Institutes of Health Research (CIHR) Microbiome Team grant, Dr. Finlay led a group of several investigators that included Dr. Stuart Turvey, the Director of Clinical Research at the Child & Family Research Institute (CFRI) at BC Children's Hospital and Professor in the Division of Allergy and Immunology in the Department of Pediatrics at the University of British Columbia, to do just that.

Dr. Stuart Turvey
Photo courtesy of BC Children's Hospital.

Dr. Turvey is a principal investigator with the Canadian Healthy Infant Longitudinal Development (or CHILD) study, which involves over 3,500 children across Canada and provides an important platform for research. Through the study, which is funded by CIHR and AllerGen, children are tracked from before birth to the age of five. With biological samples from the children (including blood, urine and stool) and detailed questionnaires for the parents, the study has been designed to unravel the complex genetic and environmental factors associated with developing allergy and asthma. Thanks to this sampling, Drs. Finlay and Turvey's team was able to analyze feces from 319 CHILD study participants, with one sample from each participant at the age of three months and another sample taken after their first birthday. Although children can't be diagnosed with asthma at such a young age, there is an asthma predictive index test that can be used. Out of the 319 participants, 22 were identified as being very likely to develop asthma—and, at three months of age, there were some striking differences in the feces (and therefore in the gut bugs) of those children, compared to the rest.

"There used to be a saying that ‘asthma happens before they can read,'" explains Dr. Turvey. "Then it became ‘before they can walk.' Now we're realizing that it happens even earlier than that."

When they were three months old, the children who would most likely go on to develop asthma were either lacking or had much smaller amounts of four types of gut bugs: Faecalibacterium, Lachnospira, Veillonella and Rothia (nicknamed FLVR—and pronounced flavour—by the researchers).

At one year of age, however, there were fewer differences in FLVR levels between the two groups.

"This tells us that kids are acquiring the bacteria over time, but maybe they need to do it earlier," notes Dr. Turvey.

The first three months of life are critical for setting up the immune system, and research has shown that certain microbes affect its development. This is currently an area of intense study, and although it appears that our gut bugs help shape the immune system (by "teaching" it what is normal, what to attack, and what to ignore), researchers are working on figuring out the biochemical mechanisms involved. Still, this research is intriguing and suggests that FLVR levels in humans may play a role in the development of autoimmune diseases like asthma. Further research is ongoing to examine the protective effect that Dr. Finlay first observed in mice. In fact, when the team deliberately inoculated germ-free mice with the FLVR bacteria from human samples, those mice were actually protected from developing lung inflammation in an experimental model of asthma.

"Our ultimate goal is to prevent asthma from developing," says Dr. Turvey, so the hope is that this research will help to better identify children at greatest risk for asthma (those with low FLVR levels at three months of age) and, eventually, to establish safe and effective ways to give doses of FLVR to those children early enough to help lower their risk of developing the disease.

In the meantime, one message is clear: we shouldn't be afraid to get dirty.

"The research shows that children probably need exposure to microbes early in life," says Dr. Finlay. "Breastfeeding [mother's skin microbiota], having a pet [microbes from the dog or cat], vaginal delivery [vaginal microbiota], living on a farm [microbes in the soil and from animals], and crawling on the floor all contribute to this," he adds. "I worry that we are now too clean as a society, even in circumstances where there is minimal risk of infectious diseases."

Dr. Turvey agrees, noting that we need to change our relationship with bacteria. "They are not the enemy," he explains, "and we need to allow kids to be exposed to a variety of environments."

Award-winning video about the CHILD Study

A video about the CHILD Study (submitted by Dr. Judah Denburg from McMaster University) won first place in the 2015 IHDCYH Talks competition. The video uses animation to explain how the study is discovering the root causes of allergies, asthma and chronic disease.

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