Thursday, May 1, 2014

"Missing Microbes" Book Review

I had the pleasure recently of reading Dr. Martin J. Blaser's new book, Missing Microbes: How the Overuse of Antibiotics is Fueling Our Modern Plagues. It was a well-written book, full of interesting information about microbes and experiments described in a very accessible way. It talks about a number of ideas of how disrupted microbes may be affecting modern chronic diseases ("a mysterious array of what I call 'modern plagues': obesity, childhood diabetes, asthma, hay fever, food allergies, esophageal reflux and cancer, celiac disease, Crohn's disease, ulcerative colitis, autism, eczema" -Dr. Blaser); my impression of today's science is that some of these ideas are becoming more popular and accepted in the scientific community, while others are still controversial.

The first few chapters describe how microbes are everywhere in the environment and on our bodies, with a lot of fascinating facts, such as that all together, the microbes in ocean water weigh as much as 240 billion elephants.
"For example, the distance between E. coli and Clostridium—two common bacteria—is much greater than the distance between corn and us."
"Originally found in extreme environments, such as hot springs and salt lakes, Archaea actually may be found in many niches, including the human gut and belly button."
That last part refers to some work by Dr. Rob Dunn at NC State University, whom I've had the pleasure of meeting.

I was very glad to see Dr. Blaser acknowledge one of my favorite examples of large bacteria, Thiomargarita namibiensis: "Microbes are invisible to our naked eye, with a few exceptions that reinforce the rule." -Dr. Blaser

Then he talks about how important microbes are in and on our bodies, inhabiting almost every surface, including (we now know) some that have long been thought sterile, like lungs and maybe even the womb. He compares the microbiome to "a vital 'organ' that helps you keep alive but that you have never seen," (though I would argue that I've seen more of this "organ" in the toilet than I've seen any of my other organs).

He also mentions the idea that our human-specific microbes might define us as a species somewhat, that there's more to it than just genetics that separates us from other animal species. They also help us communicate in certain ways, especially through smell (though that might not always be desirable, haha). "Smell is important, and it is mostly microbial in origin. It even determines who is attractive to mosquitoes." -Dr. Blaser

And of course, as I talk about a lot here on BacterioFiles, microbes have important effects on our immune system/defense against diseases, metabolism, and more. Which brings us to Dr. Blaser's main thesis: that our microbes are a lot more important that we have realized.

Antibiotics and Resistance
Obviously there are some bad players in the microbial world, though I don't focus much on those here. They caused significant suffering in human populations (and still do sometimes) before the development of vaccines and especially antibiotics. Dr. Blaser discusses how antibiotics have been seen basically as miracle drugs, turning diseases into inconveniences that pretty much used to be death sentences, and making much of medicine today (especially surgery) much safer, or even simply possible. Dr. Blaser relates an amazing anecdote about a symposium in which an account of the first patient treated with penicillin in the US in 1942 was followed by the attendance at the symposium of this same patient, who had lived another 50 years thanks to the antibiotic.

The problem, though, is partly one of human psychology: we have trouble planning for the future when faced with immediate benefit. So even though some foresaw the evolution of bacterial resistance to antibiotics even just shortly after antibiotics were developed, the drugs seemed so safe and effective that we tended to overuse them, disregarding the seemingly distant possibility of resistance. I knew that antibiotics were given as a sort of placebo to calm worried parents of virus-infected children, and that the agriculture industry fed antibiotics regularly to food animals to help them grow bigger more quickly, but I was surprised to learn just how big a problem it is: 70-80% of the antibiotics produced go toward food animals for their growth. And all this excess in antibiotic use can end up in unintended places, including our bodies, through contaminated water or milk or other food, such that it can be difficult to avoid exposure. No wonder we have a problem.

Missing Microbes?
But drug-resistant pathogens, according to Dr. Blaser, is only part of the problem. The other part is that antibiotics kill not only the bad microbes but good ones too, and some of our good microbes might be very important for certain aspects of health. (Another factor is that certain practices might prevent us from acquiring good microbes in the first place, like C-sections prevent the normal kind of colonization the infant gets when being born through the vagina.)

In particular, Dr. Blaser focuses a few chapters on the stomach microbe Helicobacter pylori (since that's one thing he has researched). This microbe has been associated with stomach inflammation, peptic ulcers, and even stomach cancer; this association actually won a Nobel prize. But H. pylori can be easily eliminated from people with antibiotics, and seems to be disappearing from the population. This might seem good, but Dr. Blaser's experiments seem to show that the loss of H. pylori is associated with other problems, such as gastroesophageal reflux disease (GERD, or chronic acid reflux) and esophageal cancer as a result of that. There was also an association with asthma and allergies in children. So Dr. Blaser asks, is H. pylori's elimination really ultimately a good thing?
"We were finding that H. pylori, discovered as a pathogen, is really a double-edged sword: as you age, it increases your risk for ulcers and then later for stomach cancer; but it is good for the esophagus, protecting you against GERD and its consequences, including a different cancer. As H. pylori is disappearing, stomach cancer is falling, but esophageal adenocarcinoma is rising."
He also focuses on antibiotics' effects on gut microbes in general and what this could mean for health, citing studies in mice that his team performed that found that constant low doses or pulses of antibiotics are linked to increased growth, obesity, and type 1 diabetes. He speculates they could be linked to other problems too, and warns that unless things change, we could face a serious shortage of microbial symbionts, leading to susceptibility of many serious problems.

He made clear that he's not saying antibiotics aren't wonderful inventions when used appropriately, but they can be much more harmful than we realized when abused.
"At a time like this [when a child is quite ill], parents should carefully reconstruct the daily events leading up to the onset of symptoms and tell the physician everything they recal...many acutely ill children will need antibiotics immediately to avoid permanent injury or to save their lives. It would be a terrible mistake for a doctor to delay such treatment out of concern for causing collateral damage to resident microbes. Serious bacterial infections will always be with us."
To solve and prevent the worst outcome (which he calls "antibiotic winter"), he suggests being smarter about using the drugs we have, developing new therapies that are more targeted to the specific pathogens we want to kill, and studying indigenous societies to learn more about (and possibly preserve) the microbes that we evolved to coexist with. He admitted the possibility that probiotics might be helpful, but isn't very confident in them.
"Despite my colleague's success story, I'm generally skeptical about the many claims surrounding all the probiotics crowded on our grocery store shelves, pharmacies, and health-food stores. They are almost completely untested. In our free country, it turns out that marketing probiotics is a kind of freedom of speech. The packages make all sorts of vague claims about health promotion, yet in most cases no rigorous trials were done to show that the ingredients were actually effective."
My Thoughts
I alternated between really enjoying this book and being very wary of its claims. It's a controversial subject among researchers in the field, as Dr. Blaser makes clear by claiming his colleagues think of him as "a heretic," and that "it was fashionable at conferences to denounce" similar work possibly showing benefit from H. pylori colonization.
"I began to think that maybe under some circumstances the inflammation caused by H. pylori could be good for us. My original ideas were fuzzy; I didn't know what good there could be. I only knew that when ancient dominant organisms disappear, there are bound to be consequences. This was heresy to most of my colleagues; having discovered H. pylori as a pathogen, they focused on the costs and considered it imperative to speed up its departure from this planet."
This type of language makes me very wary, since it's the same kind as many alternative medicine promoters use to promote their questionable or even pseudoscientific claims.

It also reminds me of arguments of the anti-vaccine group, that as vaccine use has increased, so have chronic diseases, the same one Dr. Blaser mentions (autism, food allergies, asthma). I think antibiotics as a factor is much more plausible than vaccines, but it still makes me wary.

Another quibble I have with the language is that it seems at times a bit over-hyped and flowery:
"Unless we change our ways, we are facing an 'antibiotic winter,' a much greater peril, a worldwide plague that we cannot stop. Population biology is against us; we are no longer protected by isolation. We now live in one hugely connected village, and there are billions of us. And today many millions of us live with degraded defenses. When the plague comes, it could be fast and intense. Without high ground, like a river that overflows its natural banks, there is no sanctuary."
Overall, although the thesis does resonate with me and fits in well with the content my podcast, I don't think it's appropriate at this point to be so confident in it and go as far as to make certain definite recommendations without further confirmation. The science is not yet solid, but it may be in the future.

So about the book in general, I feel that Dr. Blaser has an enthusiasm for microbiology similar to my own, demonstrated in the wealth of fascinating information he presents about the subject. And even insofar as his recommendations go, doing what we can to reduce unnecessary antibiotic use is almost certainly a good idea. However, if faced with a potentially serious infection that antibiotics can treat, don't hesitate or be afraid to use them (which is something the book agrees with too).

Bottom line: Good info, interesting presentation, interesting and plausible hypotheses but not quite settled science.

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