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The first study of a microbial community living on the human body was made back in 1683, when Antony van Leeuwenhoek wrote a letter to the Royal Society including his observations through the microscope of his own dental plaque, in which he described seeing “many very little living animalcules, very prettily a-moving.” But despite this very early interest in the microbe communities on the body, over the next three centuries, microbiologists focused mainly on “isolating” bacteria: removing them from their natural contexts and growing them in culture dishes in the lab. This approach was the only way to observe and understand bacterial cells in great detail. But it also created huge gaps in knowledge about bacterial life. It focused on the fraction of microorganisms that can be grown in culture, and it overlooked the highly complex and diverse ways in which they actually live together — an approach akin to studying humans by confining them in prison cells while ignoring the cities and communities that make up their natural habitat.
This narrow view of microorganisms began to change when new genetic sequencing technologies — which fished the genes directly out of water or soil samples — made it possible to collect information about microorganisms without having to isolate them. These studies revealed an incredible amount of genetic abundance and diversity; the microbial world was a far bigger and denser landscape than anyone had previously known. A further leap in technology has been the ability to sequence large numbers of genes rapidly. Even without “seeing” the organisms themselves, scientists can now sequence tens or hundreds of thousands of genetic fragments from an environmental sample. The resulting science of metagenomics eschews traditional ideas about studying the natural history of a particular organism in favor of a global view of the genes that exist in a community.
Using these new metagenomic methods, environmental microbiologists have delved into uncharted territories — acidic lakes, deep-ocean hydrothermal vents, and frozen tundra, to name but a few — to see what life might exist there. Gradually, some have applied the new tools to explore the “environments” of humans and other animals, with recent surveys, for instance, of the bacterial communities in various microclimates of the human body, from rear molars to intestines to nasal passages. And with these studies and the launch of the Human Microbiome Project, the fields of medical and environmental microbiology have begun to merge. The resulting hybrid discipline embraces the complexity of a larger system; it’s integrative rather than reductive, and it supports the gathering view that our bodies, and the bodies of other animals, are ecosystems, and that health and disease may depend on complex changes in the ecology of host and microbes.
In 2007, Cornell University microbiologist Ruth Ley coauthored a paper arguing that human microbiome studies could bridge the divide between biomedical and environmental microbiology. Like Jeffrey Gordon, her coauthor and mentor, Ley studies bacteria in the human gut. But while Gordon, Ley, and their fellow microbial sleuths might have hoped for a core set of organisms that would define the human microbiome, so far the reality is proving far more complicated. While only a few major groups of the world’s bacteria live in the human body, within these groups are countless bacterial species that vary greatly from person to person. “The more people look at it, it seems like an endlessly diverse system,” says Ley. The landscape of the body presents a wide range of habitats. In the nutrient-rich land of the intestines, communities appear to be fairly stable over time, while early indications show the harsher environment of the skin attracting itinerant communities that come and go. Communities can be as localized as the neighborhoods of a city; the inner elbow contains a different group of residents than the forearm.
Furthermore, in contrast to habitats such as the deep sea, where emigration and immigration are rare events, many microbial communities associated with humans are affected by constant interactions with microorganisms coming in from the environment. Microbes in the gut, for instance, encounter bacteria that ride in on the food we consume. These visitors introduce a huge, unpredictable component that makes any determination of a core microbiome all the more difficult. In order to develop well-framed research questions, it’s crucial that microbiologist learn how to differentiate between co-evolved species and these itinerant “tourists.”
What we do know, however, is that our own personal microbiomes tend to be partly inherited — most of us pick up bacteria from our mothers and other family members early in life — and partly shaped by lifestyle. Ley, who has surveyed the gut bacteria of several species, says that diet is an important factor in determining the communities that live in an organism. Even with our processed foods and sterilized kitchens, Ley says, humans are not radically different from other animals that share our eating habits.
The individuality of each person’s microbiome might complicate the project of studying human-microbe relationships, but it also presents opportunities — for instance, the possibility that medical treatments could be tailored to a person’s particular microbiota. Much like a genetic profile, a person’s microbiome can be seen as a sort of natural identification tag. As David Relman, a microbiologist at Stanford University, puts it, “It’s a biometric — a signature of who you are and your life experience.” With support from the Human Microbiome Project, Relman is currently developing novel microfluidic devices that can isolate and sequence the genomes of individual bacterial cells. (Extracting genetic information from a complex sample normally mixes together hundreds if not thousands of unique species, so this single-microbe technology could well revolutionize the speed and scope of the entire field of metagenomics.) Personal microbiome information will also have implications for practical concerns, such as how we deploy antibiotics. Might those antibiotics we down at the first sign of an upset stomach be waging an unjustified civil war? Where do the massive quantities of antibiotics we feed to our livestock ultimately end up, and do they disrupt delicate ecological balances? We have lived with microbes for our entire evolutionary history; how has the widespread use of chemicals that kill them changed those long-forged evolutionary relationships?
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