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December 16, 2009 | 30 comments
Bugs Inside: What Happens When the Microbes That Keep Us Healthy Disappear?
The human body has more microbial than human cells, but this rich diversity of micro-helpers that has evolved along with us is undergoing a rapid shift--one that may have very macro health consequences
By Katherine Harmon   
BUG OFF: Are hygienic and medicaladvances killing germ allies essential to our health?

Bacteria, viruses and fungi have been primarily cast as the villains in the battle for better human health. But a growing community of researchers is sounding the warning that many of these microscopic guests are really ancient allies.

Having evolved along with the human species, most of the miniscule beasties that live inand on us are actually helping to keep us healthy, just as our well-being promotes theirs. In fact, some researchers think of our bodies as superorganisms, rather than one organism teeming with hordes of subordinate invertebrates.

The human body has some 10 trillion human cells—but 10 times that number of microbial cells. So what happens when such an important part of our bodies goes missing?With rapid changes in sanitation, medicine and lifestyle in the past century, some of these indigenous species are facing decline, displacement and possibly even extinction. In many of the world's larger ecosystems, scientists can predict what might happen when one of the central species is lost, but in the human microbial environment—which is still largely uncharacterized—most of these rapidchanges are not yet understood. "This is the next frontier and has real significance for human health, public health and medicine," says Betsy Foxman, a professor of epidemiology at the University of Michigan (U.M.) School of Public Health in Ann Arbor.

Meanwhile, each new generation in developed countries comes into the world with fewer of these native populations. "They're actually missingsome component of their microbiota that they've evolved to have," Foxman says.

Mice have survived largely free from microbial populations in labs. But out in the world, traditional microbes are an important line of defense against external and possibly dangerous invaders. By occupying and even protecting their historic niche, this small fauna can keep out more foreign bacteria and viruses, in turnhelping to maintain their human host's health. "Someone who didn't have their microbes, they'd be naked," says Martin Blaser, a professor of microbiology and chair of the Department of Medicine at New York University Langone Medical Center in New York City.

Companies have embraced aspects of microbial research, spreading antibacterials to kill broad swaths of microbes or promoting probioticfoods to introduce other groups of bacteria into the body. These extremes, however, can make scientists in the field squirm. "There is just so much we don't know," Foxman says about manipulating these dynamics. And changes can occur quickly, even when they are unintentional.

Potent treatments: Many of the changes in the human microbiome that have surfaced in recent decades are a result ofwell-intentioned—and primarily salutary—developments in medical treatment and prevention. For example, overprescription of antibiotics, real lifesavers ever since the mid–20th century, has sparked the evolution of drug-resistant strains of tuberculosis and Staphylococcus aureus. More subtle side effects of antibiotics are just beginning to be discovered. "When antibiotics were first introduced, they weremiraculous drugs—and they still are," Blaser says. "But it really wasn't fully considered that antibiotics select for resistance." And an antibiotic will not only impact the infection it is targeted for. "It will select for resistance across the microbiome," he added.

Common side effects of antibiotic treatments, such as yeast infections, are a prime example of these silent shifts. Even as...
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