What’s the short version?

There are tens of trillions of microbes in our guts, which are important for our digestion and our health. The antibiotics that we take to kill off disease-causing bacteria also indiscriminately nuke these beneficial bugs. Now, a new set of experiments in mice have shown that low, regular doses of antibiotics at an early age can disrupt these microbe communities, leading to weight gain later in life. The increase in body weight was small, but compounded by a high-fat diet. If the results apply to humans, they would add to the large body of evidence suggesting that antibiotics should be used more carefully in infants and children.

“I’m not saying people should never take antibiotics,” says Martin Blaserfrom the NYU Langone Medical Centre, who led the study. “But we need to be more judicious. Antibiotics can have long-term consequences. I hope that knowledge will enter the examining room, so that parents don’t demand antibiotics and doctors are more cautious about using them.”

This sounds familiar…

Two years ago, Blaser’s team showed that antibiotics can change the gut microbes of young mice, which then grow up fatter. This new study confirms and builds upon those earlier results. More generally, farmers have been fattening livestock for decades by giving them low doses of antibiotics in their food—it’s the microbe connection that’s new. And Blaser himself has been discussing these ideas a lot, in the wake of his recent book, Missing Microbes.

What did the new experiments show?

The new studies represent a huge amount of work, largely done by graduate student Laurie Cox. First, she exposed mice to low doses of penicillin at two points in time: either when they were being weaned at four weeks old, or right from the start of their lives (by dosing their mothers). By 20 weeks of age, the mice that experienced penicillin from birth were heavier and fatter, especially the males. They also had very different gut microbes.

A high-fat diet exacerbated this effect, especially in females. If female mice were raised on fatty chow and penicillin, they put on twice as much fat as those that ate the fatty chow alone. (It’s not clear why there’s a gender difference.)

In these experiments, the mice were on antibiotics for their entire lives. Next, Cox showed that much shorter bursts are enough. Four weeks of early exposure can change the rodents’ gut microbes. These communities returned to normal after eight weeks, but the mice still got fatter, and their immune systems were still weaker.  This suggests that there’s a critical window where microbial upheavals have long-lasting consequences. This makes sense: our gut microbes are an active part of our development. As we grow up, they help to set our metabolism and train our immune systems. Just as schooling and education can have lasting effects on our lives, microbial education might permanently affect a mammal’s health.

Finally, Cox transplanted the microbes from the antibiotic-treated mice into germ-free ones that had no microbes of their own. These recipients alsobecame heavier and fatter. “The fact that you can transfer the [effects] by transferring the microbes is pretty solid evidence of causality,” says Jack Gilbert from the University of Chicago. “It is excellent confirmation of what [Blaser] has been expounding for a while.”

Which microbes were affected?

The penicillin depleted four particular groups, and they’re a slightly weird quartet. One of them, Lactobacillus, is very well known—common in our guts and in probiotics. But the others—two species called Allobaculum andArthromitus, and a wider group called the Rikenellaceae—are more obscure.Allobaculum was only discovered ten years ago. Arthromitus seems to only live in mice and not humans. These microbes might help to prevent their hosts from putting on too much weight, but it’s too early to say.

How does antibiotic treatment lead to weight gain?

It’s clear that the penicillin did at least four things: it changed the gut microbes; it changed the rodents’ metabolism; it increased inflammation in the gut; and it increased the risk of obesity. But, as Les Dethlefsen from Stanford University told me, it’s hard to know how these effects are connected. The microbes could be responsible for everything else. Alternatively, the drugs themselves could cause some of the effects, and the microbes others. We’re probably looking at a tangled web of causality rather than a linear chain.

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