By altering the lineup of microbes in the gut, antibiotics like penicillin might increase the risk of obesity.

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By altering the lineup of microbes in the gut, antibiotics like penicillin might increase the risk of obesity.

Taking antibiotics early in life leaves mice prone to obesity

Your body isn’t the only thing that grows quickly during the first years of life. Your microbiome, the population of bacteria that lives in your gut and elsewhere in your body, has a growth spurt, too—and disrupting it might lead to health problems down the line. A new study of mice shows that interrupting the development of gut microbial populations with low doses of antibiotics early in life disturbs their metabolism and boosts the risk of obesity later on.

In recent years, researchers have realized that the microbes living in your gut are crucial for several functions, including building a strong immune system. Infancy is a particularly important time for developing a robust microbiome, a process that begins with the microbes a newborn picks up on its way through the birth canal. Children born by cesarean section, as well as those who receive antibiotics during their first year of life, have a higher risk of developing immune disorders such as asthma and type 1 diabetes. Epidemiological studies show an elevated risk for obesity among these children as well, although the effect seems to be very small.

But Martin Blaser, a microbiologist at New York University in New York City, suspected that the microbiome’s development has a bigger impact on metabolism later in life. Studies with livestock such as pigs and chickens showed that low doses of antibiotics administered when animals are young caused them to grow faster and increased the amount of fat they gained. Blaser and colleagues wanted to determine if the metabolic changes are driven by how the antibiotics altered the animal’s microbiome, and they turned to mice to investigate the link.

Blaser and his team gave a low dose of penicillin to mice during the first 4 or 8 weeks after birth and analyzed their gut microbiota and several metabolic characteristics. As expected, penicillin changed the animals’ gut microbiota by reducing the numbers of lactobacilli and several other species that are believed to be beneficial. But this effect disappeared within a couple of weeks of the last antibiotic dose. Ten weeks later, however, treated mice that ate high-fat diets started gaining weight like mad, the team reports today in Cell. Females were particularly vulnerable: They added twice as much body fat as did their untreated female cousins that ate the same high-fat diet. Mice dosed with antibiotics that fed on normal diets did not gain weight, nor did older mice that received antibiotics.

To find out whether the mice’s disturbed microbiomes or the antibiotic itself caused the metabolic changes, the team transplanted microbes from treated mice into mice previously kept completely germ-free. The recipients immediately began gaining weight when put on a high-fat diet, suggesting that the altered cast of microbiomes was responsible for the metabolic changes. Meanwhile, germ-free mice given the gut microbes of untreated mice did not gain weight.

“This is a very good study because it moves beyond correlations and proves causality,” says microbiologist Willem de Vos of Wageningen University in the Netherlands, who was not involved in the study. Jeremy Nicholson, a biomolecular scientist at Imperial College London, adds that the study reveals that changes to the overall physiology of organisms may indeed result from relatively small disruptions of the gut microbiome, “which might have major long-term health outcomes.”

De Vos cautions against jumping to conclusions about what the study means for humans, whose guts contain very different bacteria than do those of mice. Moreover, he adds, “you would never give a child a low dose of antibiotics for a long period. You want to know the impact of repetitive, short treatments with a high dosage.” Also, future studies will have to measure the impact of different antibiotics, rather than just penicillin, he says.

Blaser agrees that more work needs to be done, but he is confident that a connection between early life antibiotic use and obesity will eventually be confirmed in humans. “A lot of work on obesity has been focused on diet and calories. That has not been sufficient to explain the obesity epidemic,” Blaser says. Antibiotics could be a missing piece of the puzzle.

Posted in Biology, Health The Microbes That Make Us