Anyone who’s ever visited a research lab that studies mice knows how the animals stink. But the mice housed in rows of large plastic bubbles in Jeffrey Gordon’s lab at the Washington University School of Medicine smell surprisingly pleasant. They’ve spent their entire lives in a sterile, protected environment, inhaling purified air. Because of their meticulous upbringing, they harbor none of the microbes that normally give mice their distinctive acrid odor.
But living free of the bacteria that colonize most animals has also had a profound effect on the mice’s development. They have less fat than their microbe-ridden counterparts and have to eat 30 percent more food to maintain their weight. Their hearts are 20 percent smaller, and they have immature immune systems.
For the last decade, Gordon, a microbiologist and director of Washington University’s Center for Genome Sciences, has been trying to figure out precisely why. He and his students have spent that time investigating the complex microbial world inside both mice and humans, attempting to determine how bacteria exert their broad influence on our health. Each of us contains roughly 10 times as many microbial cells as human ones. And while some microbes make us sick, many play vital roles in our physiology. They give us the ability to digest foods whose nutrients would otherwise be lost to us, and they make essential vitamins and amino acids our bodies can’t.
And yet, because the vast majority of these microbes die when extracted from their native habitat, they have been impossible to study and have remained a mystery. “This is completely unexplored territory that is likely to have a large impact on our understanding of human health and disease,” says George Weinstock, codirector of the Human Genome Sequencing Center at the Baylor College of Medicine in Houston.
Researchers in the emerging field of metagenomics are beginning to map that unexplored territory. New ultrafast DNA-sequencing technologies allow scientists to study the genetic makeup of entire microbial communities, each of which may contain hundreds or thousands of different species. For the first time, microbiologists can compare genetic snapshots of all the microbes inhabiting people who differ by age, origin, and health status. By analyzing the functions of those microbes’ genes, they can figure out the main roles the organisms play in our bodies.
Ultimately, researchers hope to find out precisely how microörganisms lower or increase the risk of contracting certain diseases. Armed with that information, physicians might one day use an individual’s microbial profile to diagnose a disease, or manipulate the organisms in our gut to treat or prevent health problems. “There are a whole host of properties that turn out to be dependent on the presence of healthy indigenous microbiota,” says David Relman, a microbiologist at Stanford University. “As we recognize the fundamental importance of our microbial genome, it becomes increasingly important to understand the makeup of these communities and the roles they play.”