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Consortium Members Publish Collection of Studies Stemming from Human Microbiome Project

NEW YORK (GenomeWeb News) – More than a dozen studies appearing in Nature and Public Library of Science journals this week are offering a look at results from the Human Microbiome Project, a five-year-long, National Institutes of Health-led effort to characterize the microbes found in and on the human body.

"We should … view these publications as sort of the initial analyses of this very large dataset," National Human Genome Research Institute Director Eric Green said during a telephone press briefing today.

"The whole idea of a large project like — much like the Human Genome Project — is to produce a tremendous amount of data and make it publicly available to the scientific community so that analyses and more creative ideas might bubble up of different ways of analyzing this data," Green added.

Data generated through the HMP so far includes 16S ribosomal RNA gene sequence data on microbes found at 15 to 18 body sites samples each in hundreds of individuals, along with metagenomic sequence data for a subset of these samples and some 800 new microbial reference genome sequences.

In addition to data from the project that has already been released, the consortium plans to post all of the quality control verified datasets used in the current studies on the HMP's Data Analysis and Coordination Center web site tomorrow.

More than 200 researchers from 80 research institutions have participated in the HMP, a NIH Health Roadmap Initiative project that was launched in 2007 and funded, in part, through a $153 million investment from the NIH Common Fund. Co-funding by other institutes at NIH has brought the agency's overall investment in the HMP closer to $173 million, according to James Anderson, director of the NIH's division of program coordination, planning, and strategic initiatives.

In an effort to understand the types of microbes comprising communities associated with the human body and their abundance, the HMP team recruited 300 healthy volunteers from two US cities. Each underwent medical and dental exams prior to the study.

From there, researchers used a combination of 16S rRNA and metagenomic sequencing to evaluate microbial communities associated with the skin, gastrointestinal tract, oral and nasal cavities, and urogenital tract in each individual over time, collecting samples from 18 body sites in women and 15 sites in men.

"To prevent illnesses or restore health once they occur, we need to understand better what the normal microbiome is like and what happens to it when it changes to cause or to influence disease," NHGRI's Green explained. "This requires studying and understanding the interaction of communities of microbes in our bodies, not just single microbes one at a time."

As members of the HMP consortium reported online today in Nature and elsewhere, the data collected so far is believed to represent the majority of the microbes — and combinations thereof — that make up the microbial communities in healthy individuals from the population tested.

"Overall, our sampling encountered between 81 and 99 percent of the genera, the enzyme families, and the community configurations occupied by the healthy Western microbiome," HMP consortium member Bruce Birren, director of the Broad Institute's genomic sequencing center for infectious diseases and co-director of the its genome sequencing and analysis program, told reporters today.

Using Roche 454 sequence data on the 16S rRNA genes present in the thousands of samples collected from 129 healthy men and 113 healthy women — combined with Illumina GAIIx-generated metagenomic sequence data representing complete gene sets in a subset of samples — the team identified more than 10,000 microbial species and some eight million microbial genes associated with the individuals tested.

Generally speaking, HMP results indicate that microbiomes vary by body site and between individuals, they reported, though the communities found at each body site tended to remain relatively stable within the same person over time.

But despite variability in the individual microbes present at a given body site, the metabolic capabilities of communities at a given body site seemed to be quite similar between individuals based on experiments looking at the overall gene content at these sites.

"Although different people may have different collections of organisms on, for example, their tongue, each person's tongue microbiome has roughly the same pathways for breaking down different energy sources, like simple sugars," Birren explained.

A second study, also appearing in Nature today, outlines the standardized methods that the international team used to generate, analyze, and interpret metagenomic and 16S sequencing data generated for the effort.

"Although metagenomic studies had been carried out before, nothing of this scale or complexity had been attempted," Birren noted, "and we carefully validated our laboratory and computational protocols to ensure they were both reproducible and accurate."

"Every step, from sampling to analysis, has been documented in detail and this information has been shared," he added.

Meanwhile, a collection of accompanying articles in PLoS ONE, PLoS Computational Biology, and PLoS Genetics touch on everything from technical considerations related to HMP methods and analyses to the types of metabolic pathways and immune genes that have been found in human microbiomes.

Now that they have started to get a picture of the community members that make up the microbiome in healthy American individuals, HMP researchers hope to get a better idea of how these microbiomes compare to those found in individuals from even larger cohorts and across human populations.

They are also interested in exploring how these communities are established in humans from infancy and hope to delve deeper into how the microbiome interacts with the environment to contribute to everything from human metabolism and health to human disease.

Along with analyses of microbial communities in healthy individuals, a handful of HMP demonstration projects aimed at unraveling the microbiome shifts associated with various disease states are already underway.

For example, at least two teams reporting in PLoS ONE today have evaluated the gut microbiome in relation to inflammatory bowel disease related events in the body, while another PLoS ONE study by Washington University researchers looks at the viruses found in the nasal microbiome of children with or without unexplained fevers.

The first stage of a demonstration projects focused on the vaginal microbiome was published earlier this year in Science Translational Medicine, setting the stage for future studies on changes to these communities to accompany the onset of infections such as bacterial vaginosis. That work also highlighted the diversity and dynamics in the microbial communities that can exist at a single body site over time and in different individuals.

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