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July 12, 2010

How Microbes Defend and Define Us
By CARL ZIMMER
Dr. Alexander Khoruts had run out of options.

In 2008, Dr. Khoruts, a gastroenterologist at the University of Minnesota, took on a patient
suffering from a vicious gut infection of Clostridium difficile. She was crippled by constant
diarrhea, which had left her in a wheelchair wearing diapers. Dr. Khoruts treated her with an
assortment of antibiotics, but nothing could stop the bacteria. His patient was wasting away,
losing 60 pounds over the course of eight months. “She was just dwindling down the drain, and
she probably would have died,” Dr. Khoruts said.

Dr. Khoruts decided his patient needed a transplant. But he didn’t give her a piece of someone
else’s intestines, or a stomach, or any other organ. Instead, he gave her some of her husband’s
bacteria.

Dr. Khoruts mixed a small sample of her husband’s stool with saline solution and delivered it
into her colon. Writing in the Journal of Clinical Gastroenterology last month, Dr. Khoruts and
his colleagues reported that her diarrhea vanished in a day. Her Clostridium difficile infection
disappeared as well and has not returned since.

The procedure — known as bacteriotherapy or fecal transplantation — had been carried out a few
times over the past few decades. But Dr. Khoruts and his colleagues were able to do something
previous doctors could not: they took a genetic survey of the bacteria in her intestines before and
after the transplant.

Before the transplant, they found, her gut flora was in a desperate state. “The normal bacteria
just didn’t exist in her,” said Dr. Khoruts. “She was colonized by all sorts of misfits.”

Two weeks after the transplant, the scientists analyzed the microbes again. Her husband’s
microbes had taken over. “That community was able to function and cure her disease in a matter
of days,” said Janet Jansson, a microbial ecologist at Lawrence Berkeley National Laboratory and
a co-author of the paper. “I didn’t expect it to work. The project blew me away.”

Scientists are regularly blown away by the complexity, power, and sheer number of microbes that
live in our bodies. “We have over 10 times more microbes than human cells in our bodies,” said

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To make sense of the genes that they’re gathering.nytimes. placed it under a microscope and discovered that it contained swimming creatures. In recent years. Getting the DNA is fairly easy. They’re finding that the microbiome does a lot to keep us in good health. Dr.” said David Relman of Stanford University. as it’s known.” Dr. Ultimately.) “This was quite surprising to us. The $150 million initiative was started in 2007 by the National Institutes of Health. Dr. Weinstock is part of the biggest of these initiatives. He and his colleagues are cataloging thousands of new microbe species by gathering their DNA sequences. The project team is gathering samples from 18 different sites on the bodies of 300 volunteers.693 genes that are unlike any known genes. the more species you get. when the Dutch lens-grinder Antonie van Leeuwenhoek scraped the scum off his teeth. Md. the scientists published details on the first 178 genomes. because these are organisms that have been studied for a long time. In May. known as the Human Microbiome Project. “In just the last year. “It hasn’t reached a plateau yet: the more people you look at. it really went from a small cottage industry to the big time.NYTimes. “It’s as if we have these other organs.com/2010/07/13/science/13micro. researchers hope. (The entire human genome contains only around 20.com http://www. But the microbiome. Meanwhile. George Weinstock of Washington University in St.. scientists have started to survey the microbiome in a new way: by gathering DNA.html?_r=1&em. They scrape the skin or take a cheek swab and pull out the genetic material. Weinstock is part of an international effort to shed light on those puzzling organs. because a single sample may yield millions of fragments of DNA from hundreds of different species. A number of teams are working together to tackle this problem in a systematic way. Relman estimates. Later generations of microbiologists continued to study microbes from our bodies. Louis.000 protein-coding genes. Sequencing and making sense of it is hard. but they could only study the ones that could survive in a laboratory.000 species. They discovered 29. other scientists are running experiments to figure out what those microbes are actually doing. The microbiome first came to light in the mid-1600s. however. 2 of 5 11/11/10 3:29 PM . they will learn enough about the microbiome to enlist it in the fight against diseases. scientists had only sequenced about 20 species in the microbiome. and yet these are parts of our bodies we know nothing about. Craig Venter Institute in Rockville. In the mouth alone. there are between 500 and 1. remains mostly a mystery. they are sequencing the entire genomes of some 900 species that have been cultivated in the lab.How Microbes Defend and Define Us ..” said Karen E. For many species.” he said. The new surveys are helping scientists understand the many ecosystems our bodies offer microbes. Nelson of the J. Before the project. this exile meant death.

” said Dr. “We have a pathetic number of enzymes encoded in the human genome.NYTimes. Scientists are even discovering ecosystems in our bodies where they weren’t supposed to exist. Only 13 percent of the species on two people’s hands are the same.” said Maria Dominguez-Bello. they published a list of 3. while others are more cosmopolitan. Some microbes can only survive in one part of the body. Only 17 percent of the species living on one person’s left hand also live on the right one.. The variation in our microbiomes emerges the moment we are born. In addition to helping us digest. We end up with different species. but those species generally carry out the same essential chemistry that we need to survive. for example. “You have a sterile baby coming from a germ-free environment into the world.How Microbes Defend and Define Us . the microbiome helps us in many other ways. whereas microbes have a large arsenal.3 million genes. the mice end up with stunted intestines. The microbes in our nose. One of those tasks is breaking down complex plant molecules. a microbiologist at the University of Puerto Rico. But babies born by Caesarean section were covered in microbes typically found on the skin of adults. A team of scientists at Imperial College London recently went hunting for DNA instead.com/2010/07/13/science/13micro.000 microbes. she and her colleagues studied how sterile babies get colonized in a hospital in the Venezuelan city of Puerto Ayacucho. like the tongue. “Surrounding us and infusing us is this cloud of microbes. 3 of 5 11/11/10 3:29 PM . Our bodies wait for signals from microbes in order to fully develop. In March. They took samples from the bodies of newborns within minutes of birth. They found that babies born vaginally were coated with microbes from their mothers’ birth canals.html?_r=1&em. When scientists rear mice without any germ in their bodies. European and Chinese researchers recently catalogued all the microbial genes in stool samples they collected from 124 individuals.com http://www. The mouth in turn is divided up into smaller ecosystems. Out of the 500 to 1. This variation means that the total number of genes in the human microbiome must be colossal.” said Jeffrey Gordon of Washington University. Recently. for example.” said Dr. only about 100 to 200 live in any one person’s mouth at any given moment. Lungs have traditionally been considered to be sterile because microbiologists have never been able to rear microbes from them. Dominguez-Bello.000 species of microbes identified in people’s mouths. Every square centimeter of our lungs is home to 2. Each tooth—and even each side of each tooth—has a different combination of species. Gordon. We continue to be colonized every day of our lives. make antibiotics that can kill the dangerous pathogens we sniff. Analyzing lung samples from healthy volunteers. “Our bet was that the Caesarean section babies were sterile.nytimes. the teeth. they discovered 128 species of bacteria. And the species found in one person’s body may be missing from another’s.. but it’s like they’re magnets. the gums.

Obese people also have a different set of species in their guts than people of normal weight. It’s possible that they lack the defensive shield of microbes from their mother’s birth canal. the microbes may help give rise to the disease. One way the immune system fights pathogens is with inflammation.com http://www. Some scientists argue that these studies all point to the same conclusion: when children are deprived of their normal supply of microbes. Caesarean sections have also been linked to an increase in asthma and allergies in children. 4 of 5 11/11/10 3:29 PM . while attacking pathogens. The problem may lie in our ignorance of precisely how most microbes in our bodies affect our health.com/2010/07/13/science/13micro. The Imperial College team that discovered microbes in the lungs. In response to the signal. Children who live on farms — where they can get a healthy dose of microbes from the soil — are less prone to getting autoimmune disorders than children who grow up in cities. they only damage the host’s own body. Too much inflammation can be harmful. Round at Caltech reported that mice reared without a microbiome can’t produce an inflammation-reducing molecule called IL-10. In some cases. Scientists are finding that the microbiome itself guides the immune system to the proper balance. So have the increased use of antibiotics in the United States and other developed countries. In order to co-exist with our microbiome. The scientists then inoculated the mice with a single species of gut bacteria. They’re also finding that many diseases are accompanied by dramatic changes in the makeup of our inner ecosystems.html?_r=1&em. as they’re sometimes called. But probiotics.How Microbes Defend and Define Us . known as Bacteroides fragilis. for example. their immune systems get a poor education. In some people. new microbes may simply move into our bodies when disease alters the landscape..nytimes. also discovered that people with asthma have a different collection of microbes than healthy people. our immune system has to be able to tolerate thousands of harmless species. scientists have been investigating how to treat patients with beneficial bacteria. the cells developed the ability to produce IL-10. A better understanding of the microbiome might give doctors a new way to fight some of these diseases. Some surveys suggest that babies delivered by Caesarian section are more likely to get skin infections from methicillin-resistant Staphylococcus aureus.NYTimes. untutored immune cells become too eager to unleash a storm of inflammation. Sarkis Mazmanian and June L. Last month. however. In other cases.. Once the bacteria began to breed in the guts of the mice. so we have immune cells that produce inflammation-reducing signals. For more than a century. Scientists are not just finding new links between the microbiome and our health. they produced a signal that was taken up by certain immune cells. have only had limited success. Instead of killing off invaders.

13 of which cured their patients. Instead of a crude transplant.” he said. Khoruts and his colleagues have carried out 15 more fecal transplants. not “multiply resistant. Weinstock and his colleagues are gathering to run many more experiments. “In terms of hard-boiled science.com http://www.NYTimes. It is methicillin-resistant Staphylococcus aureus.html?_r=1&em..” he said. This article has been revised to reflect the following correction: Correction: July 21. They’re now analyzing the microbiome of their patients to figure out precisely which species are wiping out the Clostridium difficile infections. A better picture of the microbiome will only emerge once scientists can use the genetic information Dr. Dr. There are no short-cuts around that. Dr. Weinstock. however. Dr. “It’s just old-time science..com/2010/07/13/science/13micro.How Microbes Defend and Define Us .” 5 of 5 11/11/10 3:29 PM .nytimes. Khoruts hopes that eventually he can give his patients what he jokingly calls “God’s probiotic” — a pill containing microbes whose ability to fight infections has been scientifically validated. 2010 An article on July 13 about new research on the role of microbes in the human body misstated part of the name of a bacterium linked to skin infections in babies delivered by Caesarean section. warns that a deep understanding of the microbiome is a long way off. we’re falling short of the mark.