Farmers have long used antibiotics to make cows, pigs, and turkeys gain weight faster. Now, scientists claim that receiving antibiotics early in life may also make children grow fat. The researchers believe the drugs change the composition of the bacterial population in the gut in a crucial developmental stage that may have a long-lasting impact.
Other scientists are casting doubt on the conclusions, however. The new data are "not convincing," says Michael Blaut, a microbiologist at the German Institute of Human Nutrition in Potsdam, Germany. And David Relman, a microbiologist at the Stanford University School of Medicine in Palo Alto, California, calls the work "provocative" but says some of the data are "a bit vague and unclear."
Billions of microbial cells live in the guts of humans and other animals. Research on these vast bacterial populations, called microbiomes, is just getting started, but scientists already know that some microbial boarders play a crucial role in breaking down nutrients in our diet. Some have also suspected that low-dose antibiotics, given to farm animals to make them grow bigger, could work by altering the gut microbiome.
To test this hypothesis, a team led by microbiologist Martin Blaser of the New York University School of Medicine in New York City added antibiotics to the drinking water of mice that had just been weaned. The medicine—either penicillin, vancomycin, a combination of the two, or chlortetracycline—was given at doses comparable to those approved by the U.S. Food and Drug Administration as growth promoters in farm animals. After 7 weeks, the group of mice on antibiotics had significantly more fat than a control group drinking plain water, the team reports online today in Nature. "This confirms what farmers have shown for 60 years, that low-dose antibiotics cause their animals to grow bigger," Blaser says.
If the findings of the study are replicated in other animal models, such as pigs, they could have considerable implications for public health, says Oluf Pedersen, professor of genomic medicine at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen.
Antibiotics did not reduce the overall number of microbes in the animals' guts, but it shifted their composition. DNA comparisons showed that mice treated with antibiotics had a higher proportion of bacteria belonging to the group Firmicutes than control animals. Firmicutes might be able to extract more calories from food and deliver them to the host, Blaser argues. The results are relevant to humans as well, he says. Another paper Blaser co-authored, published online in the International Journal of Obesity yesterday, reports a link between antibiotic use in infants and obesity in childhood.
The researchers looked at data collected from more than 11,000 children born in Avon, U.K., in 1991 and 1992. Those who had been treated with antibiotics in the first 6 months of their lives had a higher chance of being overweight at 10, 20, and 38 months of age. "It is an association, and that does not mean causation," says Leonardo Trasande, the paper's first author. "But coupled with the Nature paper, it begins to tell a convincing story."
Blaser argues that his work shows that antibiotic use in babies has an unappreciated cost. And while they're sometimes necessary, antibotics are often used willy-nilly, he says.
But others say caution is in order. In the human study, the differences in weight were small, and there was no correlation between antibiotic use in the first 6 months and weight at 7 years, the last time information was collected on the children. And there are many reasons why the mice experiments should not be extrapolated to humans and children, Relman says. The study was done with just one inbred line of mice. Seven weeks is a long time in mice, which mature quickly and live to be only 2 or 3 years old, he says. "We never give antibiotics to children continuously from the time they wean to the time they reach sexual maturity."
Also, the differences in fat mass between antibiotic-fed mice and controls are small, Blaut says. And Relman points out that while they became fatter, the mice's overall weight did not increase, as happens in farm animals. "Although one doesn't expect antibiotics to work the same in all species and under all circumstances, it does seem curious that there was this one effect and not the weight gain," Relman writes in an e-mail.
Finally, Relman cautions that the composition of the mouse microbiome was measured only at the end of the experiment. "This means that we don't know whether the microbiome changes were the cause of, the result of, or unrelated to the mouse fat content change," he says. Blaser calls that a valid criticism, but adds that he has begun to address this. "We have shown in further experiments that have not been published yet that transferring the microbiome also transfers the obesity from one mouse to the next."