U.S. scientists have analyzed 5,000 samples taken from swabs and scrapings of 250 volunteers and developed the first genetic reference map of nearly all of the microbes inhabiting healthy humans.
Like the mapping of the human genome more than a decade ago, this five-year, $173 million census of the microbes - including bacteria, viruses and fungi - that inhabit healthy humans will be used as a reference by scientists the world over as they carry out research on human disease.
Researchers sampled up to 18 sites on participants' bodies and looked at everything from saliva to blood, skin and stool.
"This is a whole new way of looking at human biology and human disease, and it's awe-inspiring. It offers incredible new opportunities," Dr. Phillip Tarr of Washington University School of Medicine in St. Louis, which was one of 200 U.S. scientists who took part in the effort, known as the Human Microbiome Project.
Physicians and researchers have long known that humans share their bodies with trillions of microorganisms, Dr. Eric Green, director of the National Human Genome Research Institute, one of the National Institutes of Health that backed the research, told a news briefing.
Prior estimates suggest there are 10 bacterial cells for every single human cell in the body, but because they are so small, microbial cells make up just 1 to 3 percent of our bodies' mass. In a 200-pound adult, that is 2 to 6 pounds of bacteria, Green said.
"Most of the time, humans live in harmony with our microbial hosts, but sometimes that harmony breaks down, resulting in disease," Green said.
Understanding what makes up a normal microbiome will help doctors better understand the changes that occur when people become sick, he said.
Presented in two papers in the journal Nature and 12 papers in Public Library of Science journals known as PLoS, the researchers found that humans play host to as many as 10,000 different microbial species.
Some of the microbes found in healthy people are known to cause nasty illnesses, yet they were peacefully coexisting with an abundance of other beneficial microorganisms in this newly defined human microbiome.
Scientists say this new reference database of microbes in healthy humans will change the way doctors think about infections, moving from a model of one germ causing disease, to thinking about factors that alter the healthy ecosystem of microbes living in people.
Prior to this study, scientists would culture microbes in lab dishes, but many of the microbes that live in humans are difficult to culture this way, and so far, only a few hundred d species have been isolated in the human body.
Instead of trying to grow cultures, researchers sampled as many as 18 different sites targeting five main body areas, including the airways, the skin, the mouth, the digestive tract and the vagina.
These samples were donated from 242 healthy people ranging in age from 18 to 40 living near Houston or St. Louis.
The researchers then purified all of the DNA in the sample, sequenced the genes and used high-powered computer programs to analyze the data and identify which microbes were present in different areas of the body and in what amounts.
"The beauty of this approach is it identifies everything that is there, giving us complete views of the microbiome at a given body site, like an explorer mapping the coastline of a newly discovered continent for the very first time," Green said.
Samples for science
Like many of his fellow volunteers, Charles Rathmann, who helps recruit clinical trial participants for Washington University School of Medicine, said he underwent several screening exams -- both dental and physical -- before being deemed healthy enough to participate in the study.
Teams took samples of Rathmann's saliva, skin scrapings from inside his elbow, on top of and inside his nose, behind his ear, as well as blood samples and stool samples on three different occasions.
Rathmann said the study offered him the rare opportunity to finally participate in a clinical trial, and he likes knowing that samples of the microbes that live in his body will become part of a reference library for future research, likening the work to early vaccine trials that went on 50 years ago.
"I feel pretty good about it," Rathmann said.
George Weinstock, associate director of the Genome Institute at Washington University, who helped lead the study, said knowing which microbes live in which "ecological niches" in healthy humans will allow researchers to better target diseases that are thought to have a microbial link, such as Chron's disease and obesity.
And it will help doctors understand why dangerous pathogens living in people sometimes turn deadly.
"One of the questions we asked is how many of these organisms are novel," Weinstock said in a telephone interview.
The good news, he said, is that most of the microbes identified in the study have been seen before, but about 5 to 10 percent of the microbes identified are newly discovered.
"They don't have a name yet. We know who their cousins are, but they are definitely novel," he said.
Now that researchers have what Weinstock calls the "parts list" for what microbes reside in healthy people, scientists will begin the process of understanding how the microbiome and human cells interact, and how this affects human health.
"There is a very active and extensive dialog going on between all of those microbial cells and all of our human cells," Weinstock said. "Our bodies somehow know which microbes are OK to have.
The next stage, he said, is trying to figure out how the body establishes the good guys from the bad.
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