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Reference Genomes Advance Human Microbiome Studies

Entercoccus faecalis, a microbe that lives in the human gut. US Department of Agriculture.

Researchers have published an analysis of 178 genomes from microbes that live in or on the human body. The accomplishment sets the stage to better understand how these diverse organisms affect human health and disease.

The microorganisms living in and on the human body outnumber the body’s cells by 10 to 1. Some of these bacteria, fungi and viruses cause illnesses, but many are necessary for good health. Currently, researchers can grow only some in the laboratory. But using new genomic techniques, scientists can identify minute amounts of microbial DNA and compare sequences in databases.

The Human Microbiome Project (HMP) was launched by Â鶹´«Ã½ in 2008 to catalog and explore the diverse microbial species—or microbiome—that inhabit the human body. Part of the first phase includes sequencing hundreds of microbial reference genomes. The effort is funded through the NIH Common Fund and involves several NIH components. Sequencing work for the project is done by HMP-funded large-scale sequencing centers around the country. Samples for the first phase are being collected from 5 body areas: the digestive tract, mouth, skin, nose and vagina.

The researchers described the 178 microbial genomes that launch the HMP reference collection in the May 21, 2010, issue of Science. The scientists found almost 30,000 previously undiscovered, unique proteins. Among them were proteins produced by bacteria that live in the stomach that may contribute to gastric ulceration, a hole in the stomach lining. The scientists also found novel proteins associated with the metabolism of sugars and amino acids.

The analysis demonstrates that genomes sequenced as part of the reference collection will add directly to our understanding of the human microbiome. However, the researchers note that the microbiome is much more complex than the set of genomes thus far in the reference collection. The first stage of the project focused on bacteria, but the HMP reference collection is eventually expected to total about 900 genomes, including those of fungi and viruses.

"Although this is only the first step in making HMP medically useful, we already have learned surprising things about the diversity and complexity of the microorganisms that live in and on our body," says Dr. Jane Peterson, a leader of the HMP effort ar Â鶹´«Ã½â€™s National Human Genome Research Institute (NHGRI). "The next stages of this coordinated study will begin to associate the presence or absence of specific micro-organisms with various states of health and illness."

The HMP is currently funding pilot demonstration projects to sample the microbiomes of volunteers who are healthy or who have specific diseases. This will allow researchers to study changes in the microbiome at particular body sites in healthy controls compared to patients affected by diseases. These studies will use samples collected from 7 areas of the body: the digestive tract, the mouth, the skin, the nose, the vagina, the blood and the male urethra.