Every year, up to 10 million U.S. children receive antibiotic prescriptions that are unlikely to do them any good, according to the American Academy of Pediatrics. A new study of antibiotic use in mice by NYU Langone Medical Center researchers suggests why the dangers of repeated and potentially unnecessary antibiotic use, especially early in life, may extend well beyond immediate side effects and eventual bacterial resistance.
“We have been using antibiotics as if there was no biological cost,” says senior author Martin Blaser, MD, the Muriel G. and George W. Singer Professor of Translational Medicine and director of the NYU Human Microbiome Program. “Our latest experiments are yet another piece of evidence suggesting that overexposure to antibiotics indeed has long-lasting effects.”
The study, published in Nature Communications, found that mice treated with two classes of antibiotics in doses proportional to those commonly used in children gained more weight, developed bigger bones, and had more disruptions in the microbial communities in their guts than untreated mice.
Although the implications for humans are still unclear, multiple studies in rodents and children by Dr. Blaser and other researchers have suggested that early-life antibiotic exposure can indeed alter the bacterial landscape of the gut and increase the risk of obesity and other metabolic disorders. Dr. Blaser, who was recently appointed chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria, says the data could help improve guidelines for pediatric antibiotic prescriptions to minimize the potential harm.
For the study, female mouse pups received three short courses of tylosin, an antibiotic used in veterinary medicine that represents an increasingly popular class of pediatric antibiotics called the macrolides; amoxicillin, a commonly used broad-spectrum antibiotic in the beta-lactam class; a mixture of both drugs; or no drugs at all. To mimic the effects of standard pediatric prescriptions in the U.S., the researchers gave mice the same proportional dose that the average child receives. The mice received their first dose when they were just 10 days old.
While tylosin had the most pronounced effect on weight gain once the mice were three to six weeks old, the study found that amoxicillin had the biggest impact on bone growth. Based on extensive DNA sequencing, the research also showed that both antibiotics disrupted the development of the gut microbiome, or the trillions of microorganisms inhabiting the intestinal tract, by markedly reducing both the overall microbial diversity and specific markers linked to normal maturation. The results, Dr. Blaser says, suggest that the drugs are “stunting the maturity of the microbiome.”
The study, supported in part by the Diane Belfer Program for Human Microbial Ecology, also suggested that antibiotic-exposed microbiomes may be less adaptable to environmental changes, such as a new diet. When the researchers moved six-week-old mice to a high-fat diet, the microbiomes of the untreated mice all adapted within a day by increasing the proportion of microbes linked to fat metabolism. Among the mice on amoxicillin, some microbiomes shifted in one day, while others took two weeks. “In the tylosin-treated mice, some of the microbiomes didn’t adapt to high-fat diets until months later,” says lead coauthor Laura M. Cox, PhD, an adjunct instructor in NYU Langone’s Department of Medicine.
Antibiotics are vitally important for treating serious bacterial infections. With the average child receiving three courses of the drugs by the age of two, however, Dr. Cox and Dr. Blaser say the new study highlights the need for more targeted therapies, antibiotic stewardship, and scrutiny of the potential downsides of overuse early in life.