Dirty diapers are the unlikeliest of crystal balls, but they could hold the answer to why some children develop asthma. Just four types of gut bacteria in the stool seem to make all the difference, predicting who will get the disease and who won’t, researchers say. The finding could help identify children at high risk of asthma, and it could also lead to the development of probiotic mixtures that prevent the disease.
The new study “puts a lot of epidemiological observations from over the years into a new perspective,” says asthma researcher Marsha Wills-Karp of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, who was not involved in the latest work.
A growing body of research has led to a new appreciation over the last decade for how the microbiome—the collection of bacteria and viruses that live in the human body—shapes people’s health. And studies have hinted that differences between young babies’ microbiomes, caused by birth methods, diet, environment, and antibiotic exposure, might affect their chances of developing diseases such as asthma and allergies.
“There are all these smoking guns to indicate that the microbiota may be involved [in asthma], but there were no experiments to prove it,” says microbiologist Brett Finlay of the University of British Columbia (UBC), Vancouver, in Canada, a senior author on the paper.
As part of the Canadian Healthy Infant Longitudinal Development (CHILD) study, Finlay and colleagues collected stool and urine samples from more than 300 babies at 3 months and 1 year old, as well as information on their health at 1, 3, and 5 years. Then, they used high-throughput genetic sequencing to detect levels of gut microbes in each stool sample. Babies that had low or undetectable levels of four bacteria—Lachnospira, Veillonella, Faecalibacterium, and Rothia—at 3 months old all went on to show early signs of asthma—wheezing and skin allergies—at a year old. The babies who didn’t develop these symptoms invariably had high levels of the four microbes in their 3-month stool samples.
The association held “quite consistently” and was “very” statistically significant, Finlay says. In addition to differences in stool bacteria, the team found differences in the urine of the babies who went on to develop asthma. Certain bacterial byproducts were at lower or higher levels, hinting that these chemicals—produced in the gut but distributed throughout the body—could act on the immune system to make it more susceptible to the disease.
Next, Finlay’s group used stool samples from the asthma-prone 3-month-olds to colonize the guts of mice that had been raised in a bacteria-free environment. The animals went on to develop inflamed lungs indicative of asthma. But if the researchers added a mixture of the four missing microbes to the mice’s digestive tracts along with the feces, the mice no longer had a heightened risk of developing asthma, the scientists report online today in Science Translational Medicine.
The discovery has one immediate application: identifying children with a high risk of asthma in their first 100 days of life, says pediatrician Stuart Turvey of UBC Vancouver, a co-author on the paper. “Those children could be followed or treated more quickly if they end up with asthma,” he adds. But it also suggests that providing this group with the unique mixture of four bacteria—a combination not found in current commercial probiotics—could prevent the onset of asthma.
But developing therapeutics will be harder than just mixing the microbes together into pill form, Wills-Karp says, because babies already have guts that are teeming with other bacteria. These “first colonists” may prevent new strains from easily taking over. And another study has suggested different bacteria as protective. “It’s not clear right now that there are ways to induce the growth of these particular bacteria in kids,” she says. “But it certainly starts to open the door toward that possibility.”
Finlay and Turvey’s team is continuing to follow the health of the first group of children, studying which go on to develop true asthma—so far, more than a third of those who developed the early signs of the disease have the full-blown version. In addition—since the microbiomes of people in various cultures are known to differ—they’re repeating the experiment in a larger, more diverse set of children, including some from Ecuador, to see whether the four strains of bacteria are universally important.