Thursday, June 14, 2012

Man's microbes help map 'normal' in humans

Photo courtesy Charles Rathmann

Charles Rathmann, 40, a St. Louis research director was the first of 242 volunteers accepted for a research project that collected samples of their cells to map the microbial make-up of healthy humans.

By JoNel Aleccia

Charles Rathmann never thought of himself as a model for American manhood, but when it comes to the bugs on his body, he is.

The 40-year-old St. Louis research director is among 242 volunteers whose skin, nose, mouth, gut and other samples have been collected and analyzed to create what scientists are celebrating as the first map of the normal microbial make-up of healthy humans.

?I am an ordinary guy,? Rathmann told msnbc.com. ?But they can use the normal flora on my body to set a baseline.?

Indeed, the release of coordinated research Wednesday from the Human Microbiome Project Consortium organized by the National Institutes of Health promises to revolutionize the study of the microorganisms that inhabit people, experts told reporters.

"This is a whole new way of looking at human biology and human disease," said Dr. Phillip Tarr, a researcher and professor of pediatrics at the Washington University School of Medicine. "It's awe-inspiring and it also offers incredible new opportunities."

Instead of the one-germ, one-disease theory that has governed past thinking, doctors and patients alike will need to consider the entire ecosystem of bacteria at work in the body, much like the ecosystem of a forest in nature.?

"This is going to be a whole new ballgame," Tarr added.?

Scientists are just starting to use the new HMP?data to understand disease, including the role of the gut microbiome in maladies such as Crohn's disease or ulcerative colitis, the skin microbiome in psoriasis, and the urogenital microbiome in reproductive and sexual diseases, among many other projects, experts said. It could become crucial in figuring out remedies for serious and potentially deadly C. difficile infections, which are blamed on disruptions in the normal flora of the gut, Tarr said.

Scientific reports being published this week include two in the journal Nature and 12 in journals from the the Public Library of Science or PLoS. The reports represent work from some 200 members of the HMP Consortium from nearly 80 universities and scientific institutions reflecting five years of research, according to the NIH.

For the first time, researchers used sophisticated genome sequencing techniques to find that instead of the few hundred bacterial species previously identified through laborious cultures, there are more than 10,000 microbial species inhabiting the human body.

Microorganisms outnumber human cells 10 to 1 and they make up between 1 percent and 3 percent of the body?s mass, the researchers found. In a 200-pound adult, that means there are between 2 pounds and 6 pounds of bacteria, "a rather remarkable amount," said Dr. Eric D. Green, director of the National Human Genome Research Institute.?

The new data, which will provide a shared database for the scientific community, showed that?people harbor a whole range of microbes, including beneficial bugs and also pathogens known to cause disease.?The microbes in healthy people appear to be much more diverse from site to site than expected, and also from person to person,?researchers found.?In addition,?they were surprised to learn that the specific bacteria at a site are less important than the functions they?perform.?

"It appears that bacteria can pinch-hit for each other," Curtis Huttenhower, a researcher at the Harvard School of Public Health explained in a statement. He was co-lead author of one of the HMP papers published in the journal Nature.?

Information like that is exactly why Rathmann agreed to be scraped, poked and prodded for science.

?I liked the fact that this was going to be a way for them to learn more about these little bacteria that exist invisibly on us,? he said.

Researchers collected a total of 5,298 samples, plucking them?from up to 18 body sites of Rathmann and the other volunteers, including 129 men and 113 women, from Houston and St. Louis.

Photo courtesy National Institutes of Health

This gut bug, the bacterium Enterococcus faecalis, is among those analyzed through novel genome sequencing techniques as part of the Human Microbiome Project Consortium coordinated by the National Institutes of Health.

Participants included some of Rathmann?s friends and colleagues, even his ex-wife, in part because Rathmann?s actual job is to round up subjects for clinical trials at the Washington University School of Medicine.

?My group tries to recruit volunteers,? said Rathmann, who is director of the Recruitment Enhancement Core at the WUSM Center for Clinical Studies.

?We get involved any time we see a trial that is interesting. It helps move the medical community forward.?

In this case, Rathmann and the others had to prove they were healthy, undergoing screening tests, blood tests, even dental exams to make sure their microbes weren?t unusual.

?If you had a cavity, you were out,? he said. ?You could take no medicines that would disrupt the flora they were trying to identify.?

The samples were collected over a period of several weeks starting in 2009, when Rathmann and others had to agree to use study-issued shampoos, soaps and toothpastes during the testing period.

The actual collection of the microbes was simple and not painful, Rathmann said. It involved scraping cells from 15 sites in men and 18 sites in women, who had vaginal swabs taken from three places.

?It was the mouth, teeth, back of the throat, inside of the elbow, back of the ear,? Rathmann recalled. ?You also had to give a stool sample on two or three different occasions.?

Researchers took these samples, all from adults ages 18 to 40, then analyzed them using a novel genetic sequencing technique that was able to identify the DNA of bacteria, ignoring the normal human DNA.

Using computers, the scientists sorted 3.5 terabytes of data to get a full picture of the human microbiome, the collection of microorganisms living in the human body.

What they found was riveting, reported the scientists, who figure they?ve now identified between 81 percent and 99 percent of all genera of microorganisms in healthy adults.

One paper published in PLos ONE found that there were certain core bacteria present in 95 percent of all subjects. But even among those core bacteria, there was a wide range among sites -- and among people.?

"Our findings include the fact that humans carry a remarkable range of microbes," said Bruce Birren, director of the Genomic Sequencing Center for Infectious Diseases. "Apparently there are many different ways to be healthy when it comes to our microbes."

Launched in 2007, the HMP has been funded through $153 million from the NIH Common Fund, which invests in high-impact research, and another $20 million from individual NIH institutes and research centers.?

Until today, Rathmann had not seen any of the research associated with his body samples. Participants didn?t receive maps of their individual microbiomes and they have no idea what particular bugs they harbored in various places.

?I definitely will follow the results of this,? said Rathmann, who hopes his example will prompt others to volunteer for clinical trials. ?Our flora will be the benchmark now for what everybody studies.?

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