Bacteriotherapy as new wonder treatment

Scientists hope, they will learn enough about the microbiome to enlist it in the fight against diseases

Bacteriotherapy as new wonder treatment

Dr Alexander Khoruts, a gastroenterologist at the University of Minnesota, in Minneapolis. NYT

She was crippled by constant diarrhea, which had left her in a wheelchair wearing diapers. 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.

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.

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, 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 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 Khoruts. “She was colonised by all sorts of misfits.”
Two weeks after the transplant, the scientists analysed 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 Dr 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.”

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 Dr 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.

Human Microbiome Project

A number of teams are working together to tackle this problem in a systematic way. 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.)

The new surveys are helping scientists understand the many ecosystems our bodies offer microbes. In the mouth alone, 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.

Scientists are not just finding new links between the microbiome and our health. They’re also finding that many diseases are accompanied by dramatic changes in the makeup of our inner ecosystems.

In some cases, new microbes may simply move into our bodies when disease alters the landscape. In other cases, however, the microbes may help give rise to the disease. Some surveys suggest that babies delivered by Caesarian section are more likely to get skin infections from multiply-resistant Staphylococcus aureus. It’s possible that they lack the defensive shield of microbes from their mother’s birth canal.

Caesarean sections have also been linked to an increase in asthma and allergies in children. So have the increased use of antibiotics in the United States and other developed countries. Children who live on farms — where they can get a healthy dose of microbes from the soil — are less prone to getting autoimmune disorders than children who grow up in cities.

A better understanding of the microbiome might give doctors a new way to fight some of these diseases. For more than a century, scientists have been investigating how to treat patients with beneficial bacteria. But probiotics, as they’re sometimes called, have only had limited success. The problem may lie in our ignorance of precisely how most microbes in our bodies affect our health.

Khoruts and his colleagues have carried out 15 more fecal transplants, 13 of which cured their patients. They’re now analysing the microbiome of their patients to figure out precisely which species are wiping out the Clostridium difficile infections. Instead of a crude transplant, Khoruts hopes that eventually he can give his patients what he jokingly calls ‘God’s probiotic’ — a pill containing microbes whose ability to fight infections has been scientifically validated.

Weinstock, however, warns that a deep understanding of the microbiome is a long way off.

“In terms of hard-boiled science, we’re falling short of the mark,” he said. A better picture of the microbiome will only emerge once scientists can use the genetic information Weinstock and his colleagues are gathering to run many more experiments.
“It’s just old-time science. There are no shortcuts around that,” he said.

The New York Times

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