Photo Dr. Alexander Khoruts, a gastroenterologist at the University Minnesota, used bacteriotherapy to help cure a patient suffering from a gut infection. Credit Allen Brisson-Smith for The New York Times
Dr. Alexander Khoruts had run out of options.
In 2008, Dr. Khoruts, a gastroenterologist at the University of Minnesota, took on a patient suffering from a vicious gut infection of Clostridium difficile. She was crippled by constant diarrhea, which had left her in a wheelchair wearing diapers. Dr. Khoruts treated her with an assortment of antibiotics, but nothing could stop the bacteria. His patient was wasting away, losing 60 pounds over the course of eight months. “She was just dwindling down the drain, and she probably would have died, ” Dr. Khoruts said.
Dr. Khoruts decided his patient needed a transplant. But he didn’t give her a piece of someone else’s intestines, or a stomach, or any other organ. Instead, he gave her some of her husband’s bacteria.
Dr. Khoruts mixed a small sample of her husband’s stool with saline solution and delivered it into her colon. Writing in the Journal of Clinical Gastroenterology last month, Dr. Khoruts and his colleagues reported that her diarrhea vanished in a day. Her Clostridium difficile infection disappeared as well and has not returned since.
The procedure — known as bacteriotherapy or fecal transplantation — had been carried out a few times over the past few decades. But Dr. Khoruts and his colleagues were able to do something previous doctors could not: they took a genetic survey of the bacteria in her intestines before and after the transplant.
Before the transplant, they found, her gut flora was in a desperate state. “The normal bacteria just didn’t exist in her, ” said Dr. Khoruts. “She was colonized by all sorts of misfits.”
Two weeks after the transplant, the scientists analyzed the microbes again. Her husband’s microbes had taken over. “That community was able to function and cure her disease in a matter of days, ” said Janet Jansson, a microbial ecologist at Lawrence Berkeley National Laboratory and a co-author of the paper. “I didn’t expect it to work. The project blew me away.”
Scientists are regularly blown away by the complexity, power, and sheer number of microbes that live in our bodies. “We have over 10 times more microbes than human cells in our bodies, ” said George Weinstock of Washington University in St. Louis. But the microbiome, as it’s known, remains mostly a mystery. “It’s as if we have these other organs, and yet these are parts of our bodies we know nothing about.”
Dr. Weinstock is part of an international effort to shed light on those puzzling organs. He and his colleagues are cataloging thousands of new microbe species by gathering their DNA sequences. Meanwhile, other scientists are running experiments to figure out what those microbes are actually doing. They’re finding that the microbiome does a lot to keep us in good health. Ultimately, researchers hope, they will learn enough about the microbiome to enlist it in the fight against diseases.
“In just the last year, it really went from a small cottage industry to the big time, ” said David Relman of Stanford University.
The microbiome first came to light in the mid-1600s, when the Dutch lens-grinder Antonie van Leeuwenhoek scraped the scum off his teeth, placed it under a microscope and discovered that it contained swimming creatures. Later generations of microbiologists continued to study microbes from our bodies, but they could only study the ones that could survive in a laboratory. For many species, this exile meant death.
In recent years, scientists have started to survey the microbiome in a new way: by gathering DNA. They scrape the skin or take a cheek swab and pull out the genetic material. Getting the DNA is fairly easy. Sequencing and making sense of it is hard, however, because a single sample may yield millions of fragments of DNA from hundreds of different species.
A number of teams are working together to tackle this problem in a systematic way. Dr. Weinstock is part of the biggest of these initiatives, known as the Human Microbiome Project. The $150 million initiative was started in 2007 by the National Institutes of Health. The project team is gathering samples from 18 different sites on the bodies of 300 volunteers.
To make sense of the genes that they’re gathering, they are sequencing the entire genomes of some 900 species that have been cultivated in the lab. Before the project, scientists had only sequenced about 20 species in the microbiome. In May, the scientists published details on the first 178 genomes. They discovered 29, 693 genes that are unlike any known genes. (The entire human genome contains only around 20, 000 protein-coding genes.)
“This was quite surprising to us, because these are organisms that have been studied for a long time, ” said Karen E. Nelson of the J. Craig Venter Institute in Rockville, Md.
The new surveys are helping scientists understand the many ecosystems our bodies offer microbes. In the mouth alone, Dr. Relman estimates, there are between 500 and 1, 000 species. “It hasn’t reached a plateau yet: the more people you look at, the more species you get, ” he said. The mouth in turn is divided up into smaller ecosystems, like the tongue, the gums, the teeth. Each tooth—and even each side of each tooth—has a different combination of species.
Scientists are even discovering ecosystems in our bodies where they weren’t supposed to exist. Lungs have traditionally been considered to be sterile because microbiologists have never been able to rear microbes from them. A team of scientists at Imperial College London recently went hunting for DNA instead. Analyzing lung samples from healthy volunteers, they discovered 128 species of bacteria. Every square centimeter of our lungs is home to 2, 000 microbes.
Some microbes can only survive in one part of the body, while others are more cosmopolitan. And the species found in one person’s body may be missing from another’s. Out of the 500 to 1, 000 species of microbes identified in people’s mouths, for example, only about 100 to 200 live in any one person’s mouth at any given moment. Only 13 percent of the species on two people’s hands are the same. Only 17 percent of the species living on one person’s left hand also live on the right one.
This variation means that the total number of genes in the human microbiome must be colossal. European and Chinese researchers recently catalogued all the microbial genes in stool samples they collected from 124 individuals. In March, they published a list of 3.3 million genes.