The average child in the US receives three courses of antibiotics by the age of 2 years and 10 courses by the age of 10 years.
According to the research team, including Dr. Martin Blaser of the NYU Langone School of Medicine at the NYU Langone Medical Center in New York, NY, 262 million courses of antibiotics were prescribed to outpatients in the US in 2011 - the equivalent to 842 courses per 1,000 people each year.
Antibiotic use is highest among children under the age of 10, the researchers say, with the average child in the US receiving three courses of antibiotics by the age of 2 years and 10 courses by the age of 10 years.
Previous studies have suggested early exposure to antibiotics may impact a child's health. In September 2014, for example, Medical News Today reported on a study associating multiple antibiotic use before the age of 2 years with greater risk of obesity in early childhood, while another study linked childhood antibiotic use with increased risk of juvenile idiopathic arthritis.
However, Dr. Blaser and colleagues note that previous studies have reached their findings by analyzing the effects of low-dose multiple antibiotic use in animals, though humans receive multiple antibiotics at doses around 10-100 times higher. As such, the team says the relevance such studies have to humans can be questioned.
With this in mind, the researchers decided to mimic childhood antibiotic use in mice.
The team gave young female mice three short courses of common antibiotics: amoxicillin, tylosin - which the team notes is not currently prescribed for children but is similar to a class that are, called macrolides - or a combination of both antibiotics.
The mice were given the same number of antibiotic prescriptions at the same doses that the average child receives in the first 2 years of life, and these mice were compared with a control group that received no antibiotics.
Antibiotics altered the gut microbiome and led to weight gain, larger bones
Compared with control mice, those that were treated with either amoxycillin or tylosin or a combination of both were found to experience greater weight gain and developed larger bones.
What is more, the team found that both antibiotics also interfered with the gut microbiome - the composition of gut bacteria - of the mice. The antibiotics altered the bacterial species present, as well as the number of genes associated with certain metabolic functions.
"They changed the ecology of the microbiome in terms of the richness of the organisms, the diversity, and also what we call the community structure, or the nature of its composition," explains Dr. Blaser.
The findings revealed that tylosin has a stronger impact on the maturity of gut bacteria than amoxicillin, and that this effect strengthens as the number of antibiotic courses rises.
"We get a little interruption of the maturation process after the second course of antibiotics, and then we have even more interruption after three courses," says lead study co-author Dr. Laura Cox, of the Department of Medicine at NYU Langone School of Medicine.
What is more, the team found that the gut bacteria of the mice that received antibiotics appeared to have a lower ability to adapt to changes in environment. For example, when the mice went from a standard diet to a high-fat diet, the gut bacteria of the control mice adapted to the new environment within 1 day. Some mice who received amoxicillin, however, took weeks to adapt.
"In the tylosin-treated mice, some of the microbiomes didn't adapt to high-fat diets until months later," says Dr. Cox.
The researchers note, however, that it is unclear what implications these alterations to gut bacteria may have and whether they are associated with increased weight gain and bone growth. In addition, they caution that their results were identified in mice rather than humans.
Still, the team says their findings highlight the potential negative impact antibiotic exposure in early life may have on development:
"Because the antibiotics used represent the classes most widely prescribed to children, and that our findings were consistent with effects of early life subtherapeutic antibiotic exposures, this new model extends hypotheses that early-life antibiotic exposures could have long-term developmental metabolic effects, as supported by animal models and human epidemiological studies."
Earlier this month, MNT reported on a study in which researchers claim to have uncovered a mechanism by which bacterial cells can survive antibiotic treatment.