The Human Microbiome Project
In Nature last January, David A. Relman, M.D., and his colleagues commented that “the shared evolutionary fate of humans and their symbiotic bacteria has selected for mutualistic interactions that are essential for human health, and ecological or genetic changes that uncouple this shared fate can result in disease. In this way, looking to ecological and evolutionary principles might provide new strategies for restoring and maintaining human health.”
But while knowledge continues to accumulate detailing how bacteria interact among themselves, with human cells, and how their metabolism affects their human habitats, “there are relatively few circumstances where you can meet a patient who is benefitting from this,” says Dr. Relman, adding that our biome is “a complex and dynamic network.” Dr. Relman is a professor of medicine and of microbiology & immunology at Stanford University, and his research program focuses on the human microbiome.
And an individual’s microbiome is as unique as the DNA in their cells, investigators are discovering. In June 2012, in an article in Nature entitled “Structure, function, and diversity of the healthy human microbiome,” results of studies conducted by the Human Microbiome Project reported, “We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals,” niche meaning the intestinal tract and other body mucosa that microbes habitually inhabit.
The five-year NIH-funded $157 million project sequenced and classified 900 microbes believed to play a role in human health. Goals of the project included development of microbiome taxonomic, metagenomic, and functional data from clinical biospecimens obtained from a cohort(s) of carefully phenotyped subjects with a specific disease or health state, and the combination of the microbiome and host data to produce a community resource.
But Dr. Relman noted with regard to expectations generated around the information produced from the microbiome project, “There’s sensitivity about the expected returns. We need to be grounded about what it is we’ll be able to gain at what point in time. I think the shorter-term gains may be around diagnostics, and novel ways of classifying both health and disease.”
The long-term objective of the initiative is to develop a dataset that the community can utilize to explore whether study of the human microbiome beyond sequenced-based analyses will yield important new insights in understanding human health and disease.
The consortium of scientists have already found the diversity and abundance of each habitat’s (gut, skin, and vagina) signature microbes varied widely even among healthy subjects, with strong niche specialization both within and among individuals.
The project encountered an estimated 81–99% of the genera, enzyme families, and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata.
Analysis of the sequences of the first 178 microbes, which was published in the May 21, 2010, issue of Science, “held some surprises” particularly with regard to the extent and complexity of microbial diversity. About 90% of their DNA was previously unknown. The study also identified novel genes and proteins that contribute to human health and disease.
Data emerging from this project, consortium investigators hope, could lead to development of new diagnostic tests because individual biomes are as unique, some scientists say, as an individual’s DNA.