It was a major feat when more than a decade ago, scientists deciphered the first human genome, containing 22,000 or so genes. But a massive effort to catalog all the microorganisms that live on and inside human beings shows people’s DNA is vastly outnumbered by that of their microscopic guests, which add another 8 million genes that perform crucial functions such as breaking down nutrients or coordinating the body’s response to disease.
Precisely which of those microbial genes any particular individual carries around will vary greatly, according to the “human microbiome project,” a five-year, $173 million initiative led partly by Boston-area scientists, which published its findings Wednesday. In that diversity may lie the answers to questions about diseases that haven’t been completely explained by our own genes—for example, why some people, but not others, get inflammatory bowel disease or become obese or get sick from an infection. Eventually, the research may point to ways to manipulate microbial populations to treat or prevent diseases.
“Understanding our genes isn’t enough,” said Bruce W. Birren, co-director of the genome sequencing and analysis program at the Broad Institute, a Cambridge research institution that was one of four centers that worked together to sequence genes in nearly 5,000 samples taken from 242 healthy people. “We are part of an ecosystem with them [microbes], and we can’t fully understand human health, nutrition, and disease without understanding these organisms.”
While people’s genomes are remarkably similar, with only a fraction of 1 percent of our genes setting one person apart from another, people may have less than half of their microbiome in common with a neighbor, a consortium—involving more than 200 scientists at 80 institutions—reported in a series of 16 articles published in the journal Nature and various journals published by the Public Library of Science.
Even on a single person, the scientists found, there is diversity in the bacteria found in, say, the crook of the elbow and the lower intestine, that can be compared with the variety of creatures living in the vast array of landscapes on Earth.
There are microbes “living in the desert on skin, the rainforest in gut, and the Arctic tundra in our mouth—very different habitats,” said Curtis Huttenhower, an assistant professor of biostatistics at Harvard School of Public Health, who co-led several of the analyses. “What we’re trying to do in a healthy population is to understand how these communities adapt, to maintain some sort of healthy, stable balance.”
Most people are used to thinking of microbes—bacteria, viruses, fungi—as germs that cause disease. But the human microbiome project has triggered a rethinking of what a human being is—as made up of us, and thousands of microbes that play an integral role in maintaining health. The microbial census focused on samples taken from more than a dozen body areas, from healthy adults recruited from centers at Houston and St. Louis.
The researchers found that even though the precise species of bacteria dwelling in the gut or on the tongue might differ radically among people, the communities in specific body areas seemed to do the same specialized functions. Birren compares this to a potluck where the same people don’t need to bring the same components of a meal, but different actors can show up and still create a dinner. The exact microbes breaking down complex carbohydrates or fats in the gut may not be the same, there are communities in everybody’s gut doing much the same thing.
“The same person doesn’t need to always bring plates or forks, as long as someone brings them everyone will eat,” Birren said.
Scientists plan to use the information from the microbiome project as a baseline for healthy people, which will allow them to understand how disease disrupts these communities of microbes, and how altering those populations might promote or combat illness. Already, several studies have examined communities of microbes in patients with inflammatory bowel disease or viruses in the nostrils of children who develop high, unexplained fevers.
Researchers from the University of Chicago reported in a separate publication in Nature on Wednesday evidence that a Western diet, high in saturated fat, altered the composition of bacterial communities in the guts of mice, and dramatically increased the onset of inflammatory bowel disease in a strain of mice that carried a genetic risk factor for the disease.
Those researchers plan to study similar questions in people, to see whether a similar bloom of a particular subset of bacteria may explain why those who are genetically at risk for inflammatory bowel disease ultimately develop it.
“The paper coming out from the human microbiome project is going to be a seminal finding, because it provides a very important reference point for us in the field to understand what is normal,” said Dr. Eugene Chang, a professor of medicine at the University of Chicago who led the study in mice. “We’ve always needed this reference point ... that will serve as the foundation for all of us to know what to compare our studies to.”
It is also part of an expanded vision of personalized medicine—in which drugs and preventive strategies can be tailored to a particular person’s risk for a disease. It won’t just be about a person’s genome, but about their microbes.
Peter Turnbaugh, a systems biologist at Harvard University, has become interested in how the microbes present in a person’s body alter how they react to a drug. For example, a chemotherapy called irinotecan is metabolized into a nontoxic form in the liver before it is excreted, but then can be reactivated back into an active form by certain bacterial enzymes in the intestines, causing diarrhea.
Understanding better the human microbiome will help elucidate these kinds of complex interactions between drugs and the body, and could help minimize side effects or increase the effectiveness of treatments.
Dr. David Relman, a professor of microbiology and immunology at Stanford University, said that the raft of studies published Wednesday are a first step, but that the power of such technologies may lie in understanding every individual’s baseline and how that changes over their life, providing protection and susceptibility to disease.
“As heroic an undertaking as it was, this is just one tiny step. This is much bigger than the human genome project,” Relman said. “Each of us has one genome of our own—of our human own—and many thousands of genomes of the microbial type. And they’re all interacting in interesting ways.”