Bacteria and other microorganisms have colonized nearly every environment on Earth, from deep-sea thermal vents to polar ice to the myriad cavities and crevices of the human body. Collectively, they make up more than half the world’s biomass. Their abundance is equally impressive on a personal scale: Bacterial cells living in and on your body outnumber your own cells by a factor of 10.
In every environment they inhabit, microbes perform crucial functions: sequestering carbon, converting nitrogen and other elements into forms that plants and animals can use, metabolizing sugars, amino acids, and vitamins in the human gut, and cleaning up environmental toxins. Microbes' metabolic capabilities can also be tapped for human benefit, in wastewater treatment, soil and crop management, and biofuel and pharmaceutical development, to cite a few important examples. The better we understand how they function, the more we benefit.
The traditional way to study microorganisms is by isolating and growing individual species in laboratory culture. But the vast majority of microbes -- 99.9%, according to some estimates -- can't be cultured in a laboratory dish and so, until recently, have remained nearly invisible to science. Researchers know little about the diversity of microbial species, what functions they serve, how they interact with one another and with their host environments, and how they respond to environmental changes.
That situation is changing, thanks to the advent of high-throughput sequencing technologies coupled with computational tools for analyzing massive, complex data sets. Together, these advances have made it possible for investigators to study the composition and functions of microbial communities containing thousands of species sampled directly from their natural habitats, without the need to culture the organisms, or even to distinguish one species from another. "We're just at the beginning of what I think will be an explosion of knowledge about the microbial world," says Yale University molecular biologist Jo Handelsman, who in 1998 coined the term "metagenomics" to describe methods for studying microbial communities in aggregate. "We've been using petri plates as the prism through which we look at microbes for 150 years," she says. "Now we're looking at vastly more species. That's part of the thrill of it: that we don't know what we're going to find. It really is brand-new life forms that we're seeing."
Intense interest, rapid development
Scientists studying the microbial communities that live in and on the human body -- the human microbiome -- are examining the role of microbes in many different areas of human health: obesity, digestive diseases, esophageal cancer, psoriasis, and sexually transmitted diseases, among others. Marine scientists are exploring how the environment influences microbes' role in carbon cycling. Soil scientists are probing the soil metagenome's ability to produce antimicrobials, which offers the potential for developing new antibiotics and may underlie the spread of antibiotic resistance.
Meanwhile, the technologies that underpin metagenomics are advancing rapidly. "Back in the dark ages of 2007, when we did our first analysis of several hundred microbial communities, we had half a million sequences and that seemed like a lot," says University of Colorado, Boulder, microbiologist Robin Knight. "Now we're routinely dealing with hundreds of millions of sequences, and soon it will be billions. Every year, just about, it's another order of magnitude increase in sequencing capacity for about the same cost."
The scientific community's excitement about metagenomics is reflected in the myriad agencies and private foundations investing in it. "There's a lot of money being poured into this field," says Jacques Ravel, a microbial genomics scientist at the University of Maryland School of Medicine's Institute for Genome Sciences in Baltimore.
Federal agencies making major investments include the National Science Foundation (NSF), the Department of Energy (DOE), the U.S. Department of Agriculture, an