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This is an archive article published on June 24, 2012

The Body’s Microbial garden

New research suggests that nurturing the microbial ecosystem within our bodies may help fight off infectious diseases with less harmful side effects and even help in treatment of disorders like obesity and diabetes

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For a century,doctors have waged war against bacteria,using antibiotics as their weapons. But that relationship is changing as scientists become more familiar with the 100 trillion microbes that call us home—collectively known as the microbiome. “I would like to lose the language of warfare,” said Dr Julie Segre,a senior investigator at the National Human Genome Research Institute,U.S. “It does a disservice to all the bacteria that have co-evolved with us and are maintaining the health of our bodies.”

This new approach to health is known as medical ecology. Rather than conducting indiscriminate slaughter,Segre and like-minded scientists want to be microbial wildlife managers. No one wants to abandon antibiotics outright,but by nurturing the invisible ecosystem in and on our bodies,doctors may be able to find other ways to fight infectious diseases,and with less harmful side effects. Tending the microbiome may also help in the treatment of disorders that may not seem to have anything to do with bacteria,including obesity and diabetes.

“I cannot wait for this to become a big area of science,” said Dr Michael A. Fischbach,a microbiologist at the University of California,San Francisco,and an author of a medical ecology manifesto published this month in the journal Science Translational Medicine. Last week,Segre and about 200 other scientists published the most ambitious survey of the human microbiome yet. Known as the Human Microbiome Project,it is based on examinations of 242 healthy people tracked over two years. The scientists sequenced the genetic material of bacteria recovered from 15 or more sites on their subjects’ bodies,recovering more than five million genes. The project and other studies like it are revealing some of the ways in which our invisible residents shape our lives,from birth to death.

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A number of recent reports shed light on how mothers promote the health of their children by shaping their microbiomes. In a study published June 13 in the journal PLoS One,Dr Kjersti Aagaard-Tillery,an obstetrician at Baylor College of Medicine,and her colleagues described the vaginal microbiome in pregnant women. Before she started the study,Aagaard-Tillery expected this microbiome to be no different from that of women who weren’t pregnant. “What we found is the exact opposite,” she said. Early in the first trimester of pregnancy,the diversity of vaginal bacteria changes significantly. Abundant species become rare,and vice versa. One of the dominant species in the vagina of a pregnant woman is Lactobacillus johnsonii. It is usually found in the gut,where it produces enzymes that digest milk. It’s an odd species to find proliferating in the vagina,to say the least. Aagaard-Tillery speculates that changing conditions in the vagina encourage the bacteria to grow. During delivery,a baby will be coated by Lactobacillus johnsonii and ingest some of it. Aagaard-Tillery suggests that this inoculation prepares the infant to digest breast milk. The baby’s microbiome continues to grow during breast-feeding.

In a study of 16 lactating women published last year,Katherine M. Hunt of the University of Idaho and her colleagues reported that the women’s milk had up to 600 species of bacteria,as well as sugars called oligosaccharides that babies cannot digest. The sugars serve to nourish certain beneficial gut bacteria in the infants,the scientists said. The more the good bacteria thrive,the harder it is for harmful species to gain a foothold.

In March,Dr Richard S. Blumberg of Harvard and his colleagues reared mice that lacked any microbiome. In their guts and lungs,the germ-free mice developed abnormally high levels of immune cells called invariant natural killer T cells. Normally,these cells trigger a swift response from the immune system against viruses and other pathogens. In Blumberg’s microbe-free mice,they caused harmful inflammation. As adults,the mice were more likely to suffer from asthma and inflammatory bowel disease.

Although the microbiome project has focused largely on bacteria,the microbe diversity within us is wider. For example,our bodies also host viruses. Many species in the human “virome” specialise in infecting our resident bacteria. But in the DNA samples stored in the Human Microbiome Project’s database,Dr Kristine Wylie of Washington University and her colleagues are finding a wealth of viruses that target human cells.

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The microbiome also includes fungi. In the June 8 issue of the journal Science,Dr David Underhill,a research scientist at Cedars-Sinai hospital in Los Angeles,and his colleagues reported on a wealth of fungal species in the guts of humans and other mammals. In mice,for example,they catalogued 100 species of fungi that are new to science,along with 100 already known.

Antibiotics kill off harmful bacteria,but broad-spectrum forms can kill off many desirable species,too. Some bacteria are adapted for invading and establishing themselves in such disrupted ecosystems. A species called Clostridium difficil will sometimes invade a person’s gut after a course of antibiotics. Once established,the antibiotic-resistant C. difficile can be hard to eradicate. Now that scientists are gaining a picture of healthy microbiomes,they are optimistic about restoring devastated ones. One way to restore microbiomes may be to selectively foster beneficial bacteria. To ward off dangerous skin pathogens like Staphylococcus aureus,for instance,Segre envisions applying a cream infused with nutrients for harmless skin bacteria to feed on.

Adding the bacteria directly may also help. A growing number of doctors are treating C. difficile with faecal transplants: stool from a healthy donor is delivered like a suppository to an infected patient. The idea is that the good bacteria in the stool establish themselves in the gut and begin to compete with C. difficile. Dr Alexander Khoruts of the University of Minnesota and his colleagues want to make faecal transplants standard practice. They can now extract bacteria from stool,“removing the ‘ick’ factor,” as he puts it.

Other conditions potentially could be treated by manipulating the microbiome. Scientists have linked obesity to changes to the gut’s ecosystem. When scientists transfer bacteria from obese mice to lean ones,the lean mice put on weight. How this happens is still unclear,but some studies suggest that an “obese” microbiome sends signals to the body,changing how cells use sugar for energy and leading the body to store extra fat.

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