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March-April 2015

Volume 103, Number 2
Page 148

DOI: 10.1511/2015.113.148

MISSING MICROBES: How the Overuse of Antibiotics Is Fueling Our Modern Plagues. Martin J. Blaser. xi + 274 pp. Henry Holt, 2014. $28.00.

When penicillin first became available, it was hailed as a miracle drug. In field hospitals during World War II it saved thousands of soldiers’ lives; countless more patients were saved after it was sold commercially in the United States starting in 1945. Surgeries grew markedly safer and formerly lethal infections such as Staphylococcus transformed into treatable, often minor, medical conditions. Moreover, the side effects of antibiotics—an occasional rash or allergy—appeared to be few and far between. Compared to the vast curative effects, it seemed a small price to pay. Flush with success, researchers quickly identified several other antibiotics, and millions of prescriptions for these drugs were—and still are—written every year.

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Then the microbes fought back. Clinical journals today are full of reports describing bacterial strains that are resistant to our most powerful antibiotics. Meanwhile, efforts to develop new antibiotics that are less prone to resistance are, at best, years away from fruition. A prospective new drug called teixobactin, reported in Nature earlier this year, prompted some cautious optimism, but even if the medication fulfills its potential in human studies (which are not yet under way), it would be effective only against the class of bacteria that includes streptococcus; it has no effect on the broad class that includes Escherichia coli. And although pathogens appear to have trouble adapting to resist teixobactin, they often develop resistance via unexpected routes. As we have learned time and again, life tends to find a way.

Most of the books, articles, and lectures sounding the drumbeat against antibiotics overuse have focused on this problem of bacterial resistance, but it is only part of the story. Physician Martin J. Blaser, who directs the Human Microbiome Program at New York University, takes a distinctly different approach. For years, his lab has been studying the effects of antibiotic treatment in mice. That work, which informs the central argument of Missing Microbes, hints at another, less obvious but potentially just as serious consequence of the unfettered application of antibiotics.

Blaser notes that across the board, the incidence of an array of chronic diseases—many of which used to be passingly rare—is increasing. Over the past 60 years, the rate of juvenile diabetes in developed nations has doubled every 20 years. The number of children with eczema, a chronic skin condition, has tripled. Asthma and food allergies are on the rise, as is autism, irritable bowel syndrome, and myriad other diseases. Superficially these diseases appear unrelated, but Blaser daringly suggests that they may all share the same root cause: antibiotics. What was once our salvation from acute diseases may now be our chronic curse.

If Blaser’s conclusions seem unusual, it might be because his research focuses on a little-known category of experiments examining the effects of antibiotics. Most antibiotic studies focus on the drugs’ effects on the pathogens they are intended to destroy. Blaser instead turns his attention to the billions of other bacteria that live innocuously, or even beneficially, in and on the human body: the personal microbiome that each of us carries.

Missing Microbes begins by drawing attention to the astounding number and diversity of microbes on our planet. Pathogens are just a tiny fraction of this bounty. Bacteria can be found in boiling underwater vents, in the clouds, and deep within the rock layers of the Earth’s crust. Bacteria are also found in and on all animals, where the vast majority cause no harm. Humans, like other mammals, carry a slew of “bugs” specific to their species and body locale. These microbes do more than just take advantage of us, their hosts; they also provide critical help. Bacteria in the colon break down fibers and provide nearby cells with short-chain fatty acids, while other bacteria produce vitamin K, necessary for blood clotting. Just as they need us as hosts, we need them to sustain good health. And this is where the trouble occurs.

Many antibiotics currently on the market are broad spectrum, meaning that they do not act specifically against the pathogen causing disease. So what happens to our beneficial bacteria when we take these medicines? Blaser details a variety of mouse experiments performed in his lab suggesting that even a single course of antibiotics may have long-term effects on the microbiome, particularly if the dose is consumed early in life. He also points out that antibiotics are ubiquitous in the United States. Between 70 and 80 percent of US antibiotics sales are made to farmers who administer the drugs at subtherapeutic doses to fatten up animals for slaughter. The meat, eggs, milk, and cheese we buy at the supermarket all may contain some of those antibiotics that were initially fed to the chickens and cows. Consequently, antibiotic-resistant pathogens have proliferated, and unknowing consumers regularly ingest antibiotics at low doses.

Blaser cites research showing that an individual’s microbiome is largely set by age 3, meaning that antibiotic courses have a greater impact on the microbiomes of infants and children than on those of adults. Other aspects of modern medicine may be compounding the disruptive influence on children’s microbiomes. In an especially fascinating chapter, Blaser discusses how women’s microbiomes shift during each trimester of pregnancy, as well as both during and after birth. At every step of the birth process, from the mother’s water breaking to the infant’s urge to suckle, bacteria have adapted to be present when needed, waiting to colonize the child’s body. Cesarean sections, bottle feeding, and antibiotics administered to both mother and child may all interrupt the historical evolutionary way a child’s microbiome is populated.

From there, Blaser connects disruption of the microbiome with the various diseases that he dubs “the modern plagues”: asthma, allergies, irritable bowel syndrome, celiac disease, obesity, juvenile diabetes, acid reflux, and cancers. (He even muses on a bacterial connection to increased average height over the past century.) Evidence connecting each disease with the microbiome varies. One particularly startling example concerns Helicobacter pylori, a bacterium in the stomach that was discovered to cause inflammation, leading to ulcers or stomach cancer late in life. It was viewed as a pathogen, and in the 1970s and 1980s physicians commonly prescribed antibiotics to eliminate it. Later research revealed that H. pylori is a regular part of our human microbiome, however. The inflammation it triggers turns out to regulate stomach acidity and protect against diseases affecting the esophagus, including gastroesophageal reflux disease, or GERD, which currently affects 10 to 20 percent of adults in the United States. Blaser calls H. pylori a “double-edged sword,” an intriguing example of how disrupting our microbiomes can have unpredictable, far-reaching consequences.

In a set of mouse experiments conducted in his lab, Blaser also found a connection between antibiotic treatments and increased incidence of obesity, particularly when antibiotics are given early in life. Further experiments revealed that antibiotic treatment combined with a high-fat diet led to an even more pronounced increase in body fat. Although such experiments cannot be ethically or practically carried out in humans, Blaser discusses a British survey of children that lends credence to the idea that exposure to antibiotics in youth may lead to obesity later in life. His discussions of potential connections between microbiome disruption and autism, celiac disease, and breast cancer are intriguing though less convincing; these connections do not yet have the same weight of scientific data supporting them.

After painting a rather bleak picture of modern antibiotic practices, Blaser offers several solutions, which—perhaps surprisingly, given the book’s otherwise iconoclastic perspective—mirror those typically proposed for curbing antibiotic resistance. He suggests an approach focusing on personal responsibility, urging patients to use hand sanitizers only in hospitals and similar contexts, avoid C-sections that are not medically essential, and question practices such as taking an antibiotic to clear up that upper respiratory infection (80 percent of which are actually caused by viruses, not bacteria). In addition, he proposes launching a broad-based public health awareness campaign to reduce the “automatic” prescribing of antibiotics (an approach used successfully in France) as well as a government ban on feeding antibiotics to animals, something that has already been done in almost every European country.

Modern Microbes focuses welcome attention on the possible consequences of disturbing the delicate balance between our bodies and the billions of bacteria that we humans host. Blaser gradually and artfully connects antibiotic-related disruption of our microbiomes with the proliferation and entrenchment of chronic disease, providing enough background to make the material accessible for readers unfamiliar with the field. Although some of these connections remain speculative, the volume of evidence presented throughout the book is hard to ignore, and the warning comes across strong and clear.

Margaret Clark earned her PhD from Harvard University in 2012 by studying dengue virus entry. She now lives in Zurich, Switzerland, where she teaches biology at a private high school.