Genes of Human-Dwelling Germs Decoded May Aid in Medicine

Humans are home to more than 10,000 species of microbes, mostly bacteria that live in healthy symbiosis in places such as the gut or behind the ears, according to the first findings from a project to decipher the DNA of all the species hosted by the body.

Scientists drew DNA samples from the human nose, skin, mouth, digestive tract and vagina, according to a series of papers on the so-called Human Microbiome Project. The trillions of microorganisms that live in and on the body outnumber human cells by 10 to 1, scientists said.

The $153 million project complements the results of the Human Genome Project, said representatives of the National Institutes of Health, the Bethesda, Maryland-based science agency that first deciphered a complete copy of human DNA in 2003. The findings reveal the extent to which humans live in harmony with bacteria from the time of birth.

“The microbial population is providing some benefit to the human host and in turn the human host is harboring those bacteria and enabling them to replicate and be stable and thrive,” Phillip Tarr, one of the project’s researchers and the director of pediatric gastroenterology and nutrition at Washington University School of Medicine in St. Louis, said yesterday during a conference call with reporters.

Results from the project, begun five years ago, are reported in two papers in the journal Nature and 14 in the Public Library of Science journals.

Body’s Ecosystems

Scientists are just beginning to explore the composition of the body’s ecosystems. These findings will serve as the baseline for many future studies, said Curtis Huttenhower, an author on the Nature papers and assistant professor of computational biology at Harvard School of Public Health.

Researchers hope to use the information from the human genome and the microbiome together to assess disease risk and some day treat disease, Huttenhower said. Knowing how these organisms interact with their host can reveal more about illnesses such as inflammatory bowel disease, obesity and infectious ailments.

“The really important impact will be everything we haven’t done yet,” Huttenhower said. “Everything we can do now, using this as a definition of what’s healthy, that’s what will be really important in the long term.”

In inflammatory bowel disease, for instance, some people have differing severity of disease flares, Huttenhower said. Understanding the gut organisms of these people may explain why some go into remission from the disease and some don’t, he said.

Disease Triggers

“There have been a bunch of studies where a specific disease is being tackled and it shows the microbiome is different from the control,” Dirk Gevers, who was a co-author on the Nature papers and a group leader at the Cambridge, Massachusetts-based Broad Institute, said in a telephone interview. “There’s some part of disease that can be explained by genetic predisposition, but something must trigger that.”

The scientists sampled 242 people, 129 men and 113 women living in St. Louis and Houston, to collect tissues from as many as 15 body sites. Surprisingly, not all people carried the same microbes and the organisms weren’t all found in the same places, scientists said

One paper, published in PLoS Collections, showed that pregnant women had different bacterial colonies in their vaginas from non-pregnant women. Those changes may help prepare for the initial colonization of a baby’s gastrointestinal tract during birth, Kjersti Aagaard, an associate professor at Baylor College of Medicine and the study author, said in a telephone interview.

“Ninety-eight percent of the time, you can tell whether someone’s pregnant just by looking at the microbiome,” Aagaard said. Some of the changes may also help ward off infections during pregnancy, she said.

8 Million Genes

The microbiome contains 8 million protein-coding genes or 360 times more bacterial genes than human genes, the study found. From one-third to two-thirds of these genes’ functions are unknown, Huttenhower said.

Information about how the bacteria interact also may be useful for disease prevention. About a third of the population, for example, carries Staphylococcus aureus harmlessly in their noses, Huttenhower said. Those people are at an increased risk of staph infections, including from methicillin-resistant Staphylococcus aureus, or MRSA. Studying how the other two-thirds keep the germ out may provide clues on preventing illness, he said.

A better understanding of how the microbiome protects the body from harmful bacteria may also help in preventing Clostridium difficile, a bacterial infection that can cause severe diarrhea, Tarr said.

Predicting Infection

Deaths from C. difficile have risen, to 17,000 in 2007 from 7,000 in 1999, according to a March study from the Centers for Disease Control and Prevention. Though some precautions are already in place to prevent C. difficile from spreading, such as hand washing, looking at a patient’s native bacteria may predict who’s at risk for an infection, Tarr said. That might allow for better prevention.

All of the sites in the study were sampled as many as three times. The scientists then looked for a gene called 16S that is found in bacteria and not in humans, to separate the microbes’ DNA from the hosts’. Variations on that gene were like barcodes, allowing scientists to count and identify the bacteria in the sequence, said Bruce Birren, co-director of the genomic sequencing and analysis program at the Broad Institute.

About 119 microbes found in humans that are difficult to grow in the laboratory are now on a priority list for whole-genome sequencing, according to an announcement from the Broad Institute, a collaboration between Harvard University and the Massachusetts Institute of Technology.

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