We live crowded lives. The 100 trillion or so microbial cells that thrive in and on people may outnumber a person's own cells by a factor of 10. Many microbes are beneficial strangers, digesting food or warding off pathogens. Others can make people very sick, causing ulcers, for example, or inflammation. Still others influence how the immune system develops or how people metabolize drugs.
Yet, until Rob Knight combined bioinformatics and rapid-fire gene sequencing to produce a sort of census of microbial biomes—the communities of microbes living in and on individuals—no one knew of the astounding diversity living under our very noses. In his lab at University of Colorado at Boulder, Knight is seeking to determine how the diversity in microbial communities in different individuals contributes to a person's susceptibility to disease.
This brave new world of microbial diversity is just coming to light. Only 3 to 5 percent of all microbial strains are believed to be amenable to culture in the laboratory, which poses a problem for identifying them by traditional techniques such as looking at the shape of the cells or by the types of chemical reactions that can be carried out. But in recent years a new method of identification based on DNA sequencing has emerged, which bypasses the need to grow microbes in culture. Scientists are now able to distinguish among different strains of microbes based on the sequence of a gene—the 16S ribosomal RNA (or 16S rRNA) gene.
To keep from drowning in sequence data, Knight writes bioinformatics algorithms that allow him to construct phylogenic trees out of the mass sampling data extracted from human microbial communities. By analyzing their 16S rRNA gene sequences, Knight can clump together thousands of previously unknown bacteria into "phylotypes"—groups that seem to be related by evolutionary descent—that he can then compare across different biological samples.
Knight thought all humans would share a similar "core" population of microbe types, but that turned out not to be the case. His research is revealing that the composition of an individual's microbial population is vastly different from that of someone living down the block or lying on the other side of the bed. Such differences, Knight believes, might play a role in differences among individuals in their susceptibility to disease or in how they respond to drugs.
"Everything we find about the microbiome is unexpected," he reports. "What intuitively makes sense turns out not to be true." He expected, for example, there might be rapid microbial interchange between different environments, such as different areas of the skin. Instead, he and his collaborators have found that "what lives on your forehead is extremely different from what's on the surface of your palm, which is itself extremely different from your armpit," says Knight. In fact, Knight and his collaborators have discovered striking differences between an individual's right and left hands, between the "gut" communities in "identical" twins, and between men and women.
Knight learned to appreciate both the delicate nature and the long-term impact of ecological diversity in his native New Zealand where the release of nonnative species has had disastrous consequences. "Just about everything that's been introduced has wreaked havoc with the environment," he explains, including rabbits, mice, deer, pigs, and a species of possum native to Australia. Without any native predators in New Zealand, the possums became a national nuisance.
Knight remembers a camping trip with his dad to the Regina Valley, in a remote, pristine national park on New Zealand's South Island. "Here were all these possums screeching away in the middle of this 'untouched' part of the country," Knight says, recalling the beginning of his research journey from broadly distributed possum populations to RNA molecular evolution to the distinct microbe population of the human gut. Of people's personal ecology, Knight says, "It's not like each of us is an island. Each of us is a whole archipelago of really different communities in different places."