After five years of toil, a consortium of several hundred U.S. researchers has released a detailed census of the myriad bacteria, yeasts, viruses and amoebas that live, eat, excrete, reproduce and die in or on us.
Described in two papers in Nature and a raft of reports in other journals, the data released Wednesday describe microbes of the skin, saliva, nostrils, guts and other areas of 242 adults in tiptop health.
The $170-million, federally funded Human Microbiome Project also cataloged the genes contained within this zoo of life. The results shed light on the hum of microbial activity inside us as nutrients are chopped and guzzled, gas and other wastes are expelled, and bugs send chemical messages to one another, jostling for supremacy or attracting new neighbors to help keep their community going.
The research is important because it gives scientists a reference point of what the microbial community looks like in healthy people, and they plan to use it to study how changes in a person’s microbiome can lead to illness. A spate of studies in the last few years has documented potential links to conditions such as inflammatory bowel disease, asthma and obesity.
Each of us is home to about 100 trillion microscopic life forms — a figure that’s about 10 times higher than the number of cells in the human body. In a 200-pound adult, these organisms can weigh a combined 2 to 6 pounds.
The vast majority of our microscopic denizens appear to be bacteria; 10,000 types may choose to make Homo sapiens home, the scientists found.
Some spots on the body, such as the mouth, are rain-forest-like in their diversity, inhabited by a rich community of bacteria that is fairly similar from one person to the next.
Other locations, such as the vagina, are more like monocultures dominated by a single bacterium, though the precise strain can vary from person to person.
“Pretty much every time you look at the results from one of the samples, it’s like a Christmas present, it’s like, ‘Oh, what’s inside?’ ” said microbial ecologist Barbara A. Methe of the J. Craig Venter Institute in Rockville, Md., who worked on both of the Nature studies. “What are all these microbes doing?”
Scientists have been aware that bacteria live on the human body ever since a 17th century Dutch naturalist examined the plaque from his teeth under a microscope. They have long speculated that these tenants exert crucial influence on our health.
Efforts to study the microbes were stymied because only a tiny fraction of bugs can be coaxed to grow in the laboratory. But the rise of sophisticated DNA sequencing technology offered a new approach. In 2001, as the landmark Human Genome Project was wrapping up, researchers proposed it was time to explore our “second genome.”
The first order of business was to figure out what the microbial population looks like in healthy people. So researchers recruited healthy volunteers ages 18 to 40 and subjected them to exhaustive exams. Even gum disease was grounds for exclusion.
With swabs, workers sampled 14 body sites from the men and 17 from the women (three extra from the vaginal area). The subjects also provided stool samples.
The scientists extracted tiny amounts of DNA from the microbes in the samples, then analyzed them in two ways.
First, they probed each sample for a key gene contained in all bacteria. Since the exact sequence of that gene is unique to each bacterial species, the analysis told them what types of bacteria were present at each body site, as well as how abundant each was.
In the second analysis, scientists sequenced every bit of DNA in the samples, producing a mix of genetic information representing every critter living at a particular body site. The structure of the genes they found told them what kind of metabolic activities could be happening there.
The organisms from all the people and sites combined were found to contain about 8 million protein-coding genes — a figure that dwarfs the 22,000 in the human genome. The function of half the microbial genes is still a mystery, they reported.
The team had set out to identify a “core microbiome,” a base-line set of flora that would always be found in the mouth, say, or the large intestine. They didn’t really find this, but their analysis revealed that each place in the body seems to have a distinct set of metabolic abilities, be it digestion of sugars in the mouth or of complex carbohydrates in the large intestine. In different people, different microbes appear to be performing the same tasks.
“You can think about it like jobs in a city,” said Curtis Huttenhower, a computational biologist at the Harvard School of Public Health who worked on the Nature papers and several others. “If you go to two different cities, both will have banks and transportation and lawyers, but the specific people performing those tasks might be very different.”
There were known disease-causers in the mix, such as Staphylococcus aureus, which was detected in the noses of 29% of the volunteers and the skin of 4% of them. Perhaps 100 types of bacteria of this kind were identified, presumably tolerated at low levels but able to multiply and sicken their host when opportunity strikes.
For many scientists, the chief hope is that the data will help them understand how subtle disturbances in the microbiome could be linked to medical disorders. From the first days of life when our guts become populated, these bugs help us get the nutrition we need, stop harmful bacteria from colonizing us and play a key role in shaping our immune system.
In fact, many people think of the microbiome as an organ in its own right, said Dr. Richard Blumberg, chief of gastroenterology at Brigham and Women’s Hospital in Boston, who was a consultant on the project for the National Institutes of Health.
Now that they have a picture of what a healthy microbiome looks like, scientists say they can use it as a reference point to compare with the microscopic life inside those who are sick, and probe whether changes in their microbial communities could be contributing to their illnesses.
Already, studies have linked microbial conditions to forms of inflammatory bowel disease such as ulcerative colitis and Crohn’s disease. But there are suggestions that our flora may be involved in many more disorders, such as diabetes, psoriasis, asthma, heart disease, rheumatoid arthritis, obesity and colorectal cancer.
In time, researchers hope to develop therapies to put a perturbed or just plain broken microbiome back to rights. They might feed a person corrective bacteria, for example, or the type of food that would encourage the right microbes to grow.
In one small but dramatic example of what might one day be routine, Finnish researchers reported in March that patients with recurring Clostridium difficile infections recovered after fresh fecal material from healthy donors was transplanted into their guts.
Despite the current preoccupation with probiotics as cure-alls, scientists say they have a long way to go before they truly know how to design such therapies.
The emerging appreciation for bacteria raises important questions about whether overuse of antibiotics is contributing to disease, said Dr. David A. Relman, a microbiologist and infectious-disease clinician at the Stanford University School of Medicine, who wrote a commentary that accompanies the Nature papers. For instance, C. difficile infections can occur when antibiotic treatments kill off normal gut flora and permit the dangerous bacteria to flourish.
The microbiome project, though huge in scope, only begins to describe the life forms within us, Relman said. The soup of life will vary in those who live in other parts of the world, in people of other ages, in the same people at different times of their lives, and in those who aren’t in prime health.
“The whole business is humbling,” he said."It seems like the more we learn, the less we know.”