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 inside and on 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 helping regulate the body’s response to disease.
Precisely which of those microbial genes individuals carry around varies 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 have not 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, codirector 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 about 5,000 samples taken from 242 healthy people. “We are part of an ecosystem with [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, a person may have less than half of his or her microbiome in common with a neighbor, a consortium of 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: something made up of us and the 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 in 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. The exact microbes breaking down complex carbohydrates or fats may not be the same, but there are communities of bacteria in everybody’s gut doing much the same thing.
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 unexplained high fevers.
Researchers from the University of Chicago reported Wednesday in a separate publication in Nature 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 mice that carried a genetic risk factor for the disease. Those researchers plan to study similar questions in people.
“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.
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 also informed by his or her microbes.
Peter Turnbaugh, a systems biologist at Harvard University, has become interested in how the microbes in a person’s body alter how the person reacts to a drug. For example, a chemotherapy called irinotecan is metabolized into a nontoxic form in the liver before it is excreted, but it can then be reactivated back into an active form by certain bacterial enzymes in the intestines, causing diarrhea.
Understanding the human microbiome better 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.