Martin Blaser, NYU Langone Medical Centre,
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Millions of doses of antibiotics are administered every day, particularly to young children. While their life-saving benefits speak for themselves, could there be a downside to antibiotic exposure in early life? A new study on young mice suggests that use of the drugs might be making children more likely to become obese and causing lifelong changes to metabolism, as Martin Blaser, from NYU Langone Medical Centre, explains to Chris Smith...
Martin - I realised that farmers give antibiotics to their farm animals to improve their growth. And about 10 years ago, a light bulb went off and I thought, maybe this is what we are doing to our children. We are causing them to grow more too. So, in recent years, we have done studies in mice where we’ve given the mice doses of antibiotics at the levels that farmers give. These are low doses given every day in their drinking water and we found that the mice become fat. When we put them on a high fat diet, they become fat. When we put them on antibiotics they become fat. When we put them on both together, they become very fat. But human children aren’t getting low doses of antibiotics every day. They’re getting pulses of antibiotics to treat their ear infections and their throat infections. So now, we’ve developed a new model which we called PAT for Pulsed Antibiotic Treatment so that we’re mimicking the kind of exposures that children get.
Chris - And you're asking, does this pulsed administration of antibiotics which is more similar to what we do in real life, does that also translate into subsequent changes in growth, including obesity?
Martin - Yes, so we’re asking whether these pulsed doses of antibiotics mimicking the kinds of doses that kids get, will they change metabolism, will they change the development of the mice, and will they affect the microbes that are living in the mice?
Chris - What happens?
Martin - Well, not surprisingly, the antibiotic administration affected the populations of microbes in their body and this is what's called the microbiome. The antibiotics changed their diversity, how many different kinds there were, and they changed the composition of the community so that the mice had different kinds of communities when they were on antibiotics. Importantly, the effects lasted way beyond when the antibiotics were stopped. In some cases, they continued into when mice are in middle age even though this was given to mice during their childhood period.
Chris - What effects were there on the mouse metabolism and growth, and other important things that we were aiming to find out what would happen in children?
Martin - We found that the antibiotics had effects on their metabolism. Here, we used two different antibiotics – amoxicillin, the most widely used antibiotic in childhood and a macrolide antibiotic, that’s the second most widely used antibiotic. And they differed a little in their effect. The mice on the amoxicillin developed bigger bones. The mice on the macrolide, they developed more fat.
Chris - Can you explain why giving antibiotics should affect the composition and growth of bone in one case and becoming more fat in the other case?
Martin - Well, we’re not entirely sure what accounts for the differences in responses to the antibiotics. Although in our past studies, we’ve seen effects both on fat and on bone. And so actually, that’s an area that we’re currently working on to understand the intermediate mechanisms that account for this.
Chris - But the fact that the effects were lifelong is really quite worrying because that’s saying that if you administer antibiotics as we commonly do to many, many children when they're little, you are potentially distorting or bending the composition of the bugs that live on them and in them, and that will have metabolic consequences that could last their lifetime.
Martin - Yes. In our earlier paper, we showed that if we gave antibiotics and we perturb the microbes even for a short period of time, there could be lifelong metabolic effects even when the microbes went back to their usual compositions. So, we are concerned about this and in a sense, we are recapitulating what the farmers had been showing for decades. They showed, the earlier you start antibiotics, the bigger the effect of growth. We’re finding that too.
Chris - Doctors are not going to take away from this, the message, “Don’t give children antibiotics” because in many instances, antibiotics can be absolutely critical in a life-threatening situation. But what could we do to mitigate these effects then?
Martin - Well, your point is really good. Antibiotics are necessary drugs. They have saved countless numbers of lives and in no way am I saying, “We should abandon antibiotics.” We just need to use them more judiciously.
Chris - Extrapolating your findings albeit in mice, to young kids, are we therefore presupposing that some of the growing trend in overweight amongst youngsters could be attributable to overuse of antibiotics?
Martin - Our study was a study of mice. It’s our third study in mice, all showing that early life antibiotics are changing development, increasing body mass And there now have been several epidemiologic studies, studies of groups of children, the Avon longitudinal study that we participated in, showing that kids exposed to early life antibiotics had increased markers of obesity or adiposity, or fattiness at the age of 7. So, there’s a growing body of data in children as well that antibiotics have cost in terms of obesity. There are studies about antibiotics and asthma, and food allergies, and coeliac disease. So, we’re coming to realise that antibiotics have great benefits but they also have some potential costs.