The study, published in Mucosal Immunology, provides the strongest evidence so far that the long-observed connection between antibiotic exposure in early childhood and later development of asthma and allergies is causal.
“The practical implication is simple: Avoid antibiotic use in young children whenever you can because it may elevate the risk of significant, long-term problems with allergy and/or asthma,” said senior author Martin Blaser, director of the Center for Advanced Biotechnology and Medicine at Rutgers University.
In the study, the researchers note that antibiotics, “among the most used medications in children, affect gut microbiome communities and metabolic functions. These changes in microbiota structure can impact host immunity.”
In the first part of the experiment, 5-day-old mice received water, azithromycin, or amoxicillin. After the mice matured, researchers exposed them to a common allergen derived from house dust mites.
Mice that had received either of the antibiotics, especially azithromycin, exhibited elevated rates of immune responses—i.e., allergies.
The second and third parts of the experiment tested the hypothesis that early exposure to antibiotics (but not later exposure) causes allergies and asthma by killing some healthy gut bacteria that support proper immune system development.
Lead author Timothy Borbet of New York University first transferred bacteria-rich fecal samples from the first set of mice to a second set of adult mice with no previous exposure to any bacteria or germs. Some received samples from mice given azithromycin or amoxicillin in infancy. Others received normal samples from mice that had received water.
Mice that received antibiotic-altered samples were no more likely than other mice to develop immune responses to house dust mites, just as people who receive antibiotics in adulthood are no more likely to develop asthma or allergies than those who don’t.
Things were different, however, for the next generation. Offspring of mice that received antibiotic-altered samples reacted more to house dust mites than those whose parents received samples unaltered by antibiotics, just as mice that originally received antibiotics as babies reacted more to the allergen than those that received water.
“This was a carefully controlled experiment,” Blaser said. “The only variable in the first part was antibiotic exposure. The only variable in the second two parts was whether the mixture of gut bacteria had been affected by antibiotics. Everything else about the mice was identical.
“These experiments provide strong evidence that antibiotics cause unwanted immune responses to develop via their effect on gut bacteria, but only if gut bacteria are altered in early childhood.”
Additional coauthors are from the University of Zurich, New York University, and Rutgers.