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'Missing Microbes': How Hard Should You Resist Antibiotics? And Why

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The new book "Missing Microbes" posits that our rampant overuse of antibiotics is not just creating antibiotic-resistant "superbugs"; it is contributing to many of our modern maladies, particularly those affecting children: asthma, allergies, diabetes, obesity.

It's an idea that has lately been gaining attention and adherents. But you're especially likely to pay attention and be persuaded when you're hearing about it from a leading authority on the microbial "ecologies" in our bodies that are damaged by antibiotics: Dr. Martin Blaser, director of the Human Microbiome Program at New York University. Dr. Blaser, who wrote "Missing Microbes," is in town for a microbiology conference and will be on Radio Boston this afternoon. Our conversation, lightly edited:

As you write, antibiotics are prescribed at incredibly high rates in this country. That's the big picture, and it's clear that it's a problem, but what's the pragmatic translation? The small picture is something more like a baby who's been screaming for days and a scared parent who needs to know, just how hard should we resist antibiotics, and in what situations?

We’re starting with perhaps the most difficult question. But you see, in the United States, in order to get antibiotics, you need a prescription. And that means it's really up to the doctor. And because everyone has thought that antibiotics are 'free,' there has been a tendency by both doctors and parents to over-prescribe them and to over-want them. But once you start assigning a cost to them, then the situation changes. And so for parents, I advise them that when their child is sufficiently sick, that they should seek medical attention, and they should try to ensure that the doctor — and that's shorthand for doctor, nurse, nurse practitioner, physician's assistant — that the doctor do a careful exam. And then if the doctor says your child does not need an antibiotic, that parent should be relieved. Not thinking, 'Why is my child deprived?'

But isn't it so often unclear whether antibiotics are actually needed?

It is unclear, and in fact we know that most of the upper respiratory and ear infections that children have are caused by viruses that don’t even respond to antibiotics. As I write in my book, in the U.S. in 2010, there were 258 million courses of antibiotics prescribed. That’s five courses for every six people. So point number one is that that’s a lot. Point number two is that there’s enormous regional variation — variation that cannot be explained based on variation in the prevalence of different bacterial infections. So that means that it’s a function of how medicine is practiced. And the practice of medicine involves both the doctors and the patients. Both are parties. And what I point out is that in Sweden, where the people are at least as healthy as we are, at every age they're using 40 percent of the antibiotics that we're using. And that means, across the board, that 60 percent of the antibiotics are unnecessary. And that’s at every age, not just in childhood --though it’s especially important in childhood at every age.

Though we are making some progress, aren't we? The CDC said last week that antibiotic prescriptions for cold symptoms dropped 39 percent between 1996 and 2010.

That's wonderful — that’s what needs to be done. What doctors do has been based on antibiotics having no cost. Once you put cost in there, it's the difference between a free road and toll road.

Some recent research has also found that when you take antibiotics, your own personal risk of developing bacteria that are resistant to antibiotics also goes up — so there's not just a societal downside, there's an individual one.

That's correct. A big part of the book is about how it's not just the community cost of resistance or the individual cost of resistance, both of which are well known, but it’s the cost in terms of risk of disease, like obesity and diabetes and asthma, that we and others are linking to this early life change in the microbiome.

That idea seems to be really taking hold lately — what's happening?

A lot of things are coming together. More and more investigators are finding that this is actually true.

Is it also that we've gotten better tools to explore the microbiome so there's more confidence?

Yes, and we're doing more epidemiologic observations in people, and animal experiments.

Probiotics: in the book, you sound skeptical though not totally dismissive of them. A food scientist once told me that taking a probiotic was like putting a drop of something in a swimming pool. True?

Yes, though if the drop of something is chlorine, it has an effect. That's part of the issue, of course. But the main issue is that if you go to the grocery store, health food store, drug store, there are hundreds of things you can buy that are labeled 'probiotics,' and they’re very diverse --- and in fact, some of them may have the same bacteria but they have different labels. So that’s the first thing: there’s a proliferation of them and what I can say is that they're generally safe but they are almost completely untested for efficacy.

So caveat emptor — buyer beware.

Caveat emptor always rules.

Some aren’t even refrigerated — is it even plausible they could work?

Sure. Some are dried. I don't think that's the issue. It's that they’re hardly tested and so we don’t really know what they do. And furthermore, you could argue that this is just an exercise in pure marketing. Right now, it’s highly marketing-driven but I’m hopeful that at some point in the future, it will have a scientific basis.

There’s a lot of talk of 'prebiotic' diets — for example, eating fermented foods.

If they worked they would be fine. But it’s the same issue, do we know that they work? 'Prebiotics' is the foods that you eat to encourage the good bacteria that you either have inside you or the good bacteria that you want to take. And again, the idea that kimchi is one of those prebiotics — I don’t know where that comes from. Kimchi is delicious, I love it, but that’s a different issue. Prebiotics could be very specific sugars, or sorts of amino acids that particular bacteria like where you could favor one over the other, but do they work?

But wouldn't you know what works in the lab, and so could work in our guts?

We’re not sure yet exactly which bacteria we want to facilitate and which ones not. There are a lot of open questions.

It’s very frustrating — the theory is so persuasive, but how do we bolster our microbiomes?

We're hoping that one day there will be products that permit this. In full disclosure, I'm working as a scientific consultant for several companies that have this as a goal, and it's a very worthwhile goal but nobody’s in the marketplace yet.

In the meanwhile, labor and delivery — you describe how that's a setting where the use of antibiotics is particularly heavy, and again the question arises: How hard to resist? How hard to resist a C-section, which appears to affect the baby's microbiome, and the common prophylactic antibiotics for the mother, and the antibiotic eye drops for the baby, and the rest?

That's an area where I and others are working on talking to doctors, because the average person doesn’t have enough information to make that kind of decision. That's a medical decision, of balancing benefit and risk, and there are many cases where it’s critically important to use antibiotics. So in no way do I think that shouldn't be the case, but there are a lot of slippery slopes, where somebody has minor symptoms and people have thought, 'Because antibiotics have no cost, we're better off treating them.' But if antibiotics do have a cost, then maybe net-net you come out behind.

For example, you point out that every American baby is given antibiotic eyedrops against possible blindness caused by gonorrhea, which is actually a very rare prospect.

The question is, what’s the net benefit of treating 4 million babies a year with eyedrops?  How many cases of blindness are we preventing? And if it’s a handful, which it probably is, can’t we come up with a better strategy?

And if there’s a cost to the drops?

If you think there’s no cost then why not do it? And the answer is, we don’t really know if there’s a cost or not. I'm hoping to study that with some colleagues.

You also write about this very interesting idea of using gauze to swipe the vaginas of mothers who've delivered by C-section and then transfer some of that bacteria to the baby. Where's that at, is it still totally experimental?

Yes, it's completely experimental. Actually, my wife is speaking about it at the Boston meeting of the American Society for Microbiology that I'm attending.

So it's not something a pregnant woman should think about?

I'm not giving medical advice here; I'm reporting on the field, and this is a work in progress. But the concept of restoring what is missing because of C-sections is attractive.

One other topic: In the book, you use the term estrobolome, which I had never heard before, referring to how a woman's microbiome may affect her estrogen, her hormones. Could you explain?

Estrogen is important to every woman at essentially every age, and there’s a certain metabolism of estrogen: the ovaries produce estrogen and it circulates in the blood, it goes to the liver, and then the liver modifies estrogen, it 'conjugates' it, and now the conjugated estrogen goes out in the bile and it goes into the intestine. And if it stays conjugated, basically it’s excreted. But if it meets bacteria that have an enzyme that conjugates it, then it can be re-absorbed. So whether or not it meets such a bacterium determines its fate. And so our hypothesis is that that has a bearing on estrogen metabolism and there is data in the literature that supports it. And we think this is something that’s potentially modifiable; for example, certain cancers are driven by estrogen. It could also have to do with issues of menopause. There are many potential ways it could be modified if we had better scientific knowledge.

Back to food: I assume you'd advise that we buy antibiotic-free meats. But you also write that antibiotics are found just about everywhere — in milk, in water...

It’s not quite everywhere. It's not in the air, and it's in food because of the industrial use of antibiotics in agriculture.

Yes, buy antibiotic-free food but also 
lobby your congressman to get antibiotics out of the food supply, because they have many effects. That's the most important thing we can do, because there's lots of obfuscation and it's been known for decades that it’s bad in that it develops antibiotic resistance, but millions or tens of millions of people every day are being exposed to trace levels of antibiotics in their meat, children in their milk, people in drinking water, and we don’t really know what the consequences are. Maybe they’re trivial but maybe they're cumulatively very important.

You write in the book about experiments linking antibiotics to fatter mice. To what extent do you think we can attribute the obesity epidemic to early courses of antibiotics?

In my heart of hearts, I think it’s quite important. Remember, that's why farmers are giving antibiotics to their farm animals, to fatten them up, to promote their growth. You know why they do it? Because it works.

Readers, any burning questions for Dr. Blaser? Please post them soonest below.

Carey Goldberg Twitter Editor, CommonHealth
Carey Goldberg is the editor of WBUR's CommonHealth section.

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