Antibiotics Weren’t Used to Cure These Patients. Fecal Bacteria Were.


In a small study, doctors used so-called fecal transplants to treat a serious gut infection in patients. The transplants, from healthy donors, were as effective as antibiotics.

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C. difficile kills 14,000 people annually in the United States. A new study finds that transplanting healthy bacteria into a person’s intestines is just as effective antibiotic treatment.CreditLouise Murray/Science Source

The bacteria can take over a person’s intestines and be difficult to eradicate. The infection causes fever, vomiting, cramps and diarrhea so severe that it kills 14,000 people a year in the United States alone.

The first line of treatment for the attacking microbes, called Clostridium difficile, is antibiotics. But a group of Norwegian researchers asked if something more unusual — an enema containing a stew of bacteria from feces of healthy people — might work just as well.

The answer, according to a report today in the New England Journal of Medicine, is yes.

Until now, there has never been a clinical trial conducted in more than one medical center that has investigated so-called fecal transplants as a first therapy for C. difficile infections, said Dr. Michael Bretthauer, a gastroenterologist at the University of Oslo and lead author of the new study.

The Food and Drug Administration permits fecal transplants and professional societies endorse them, but only a last resort for treating C. difficile infections after antibiotics have failed, said Dr. Alexander Khoruts, a gastroenterologist at the University of Minnesota.

“The F.D.A. and all the professional societies are in full agreement on this point,” he said.

Several small clinical trials and doctors’ clinical experience have shown that a fecal transplant can help in that desperate situation.

“It’s definitely a paradigm shift to use it earlier rather than later,” Dr. Nasia Safdar, an infectious disease specialist at the University of Wisconsin — Madison.

The study, conducted in Norway, was small — just 20 patients randomly assigned to get the fecal bacteria or antibiotics. That’s not enough to determine whether transplants are better than antibiotics.

Instead, the research was intended to show that treatment with fecal bacteria is no worse.

Five out of nine patients who received fecal bacteria were cured immediately of their infections, compared to five of 11 in the group getting antibiotics. Three of the four remaining patients who got fecal bacteria then got antibiotics; two were cured within days.

None of the antibiotic patients whose symptoms persisted after their first round of treatment were cured with a second round of the drugs.

Although the results seem to favor treatment with fecal bacteria, the difference was not large enough to say fecal transplants were actually superior to the drugs.

The researchers are planning to start a more definitive study with 200 patients this summer.

The idea behind fecal transplants is to provide a dose of healthy gut bacteria that multiply and crowd out the dangerous germs making patients ill. The bacteria can be extracted from feces and supplied as an enema or in a capsule that patients swallow.

A small company also grows fecal bacteria in a lab and freezes them for transplants. The Norwegian study relied on that company to supply fecal bacteria, but the investigators say the company had no other role in the study.

Researchers are exploring the use of fecal transplants for a variety of conditions, Dr. Bretthauer said, ranging from bowel diseases such as Crohn’s disease and ulcerative colitis “to more far-fetched things, such as multiple sclerosis.”

So far, he added, the most promising evidence for the fecal transplant’s effectiveness is in ulcerative colitis.

One problem with using fecal transplants as a treatment of last resort for C. difficile infections, Dr. Khoruts said, is that it can take a long time for patients to overcome their aversion. On average, he said, these patients struggle through ten months of futile antibiotic treatments before they try a fecal transplant.

Still, some patients newly diagnosed with C. difficile ask Dr. Khoruts why can’t they just get a fecal transplant right away. Their reasoning makes sense, he added. Antibiotics that destroy the normal bacteria that protect against C. difficile are the main reason patients developed the infection in the first place.

Transplants, Dr. Khoruts said, “are trying to repair what was broken in the first place, rather than perpetuate the damage.”

But when Dr. Bretthauer and his colleagues proposed a study testing fecal transplants compared to antibiotics in newly diagnosed patients, other doctors were not enthusiastic.

“Using feces is a little taboo,” Dr. Bretthauer said. “If you are putting someone else’s feces into a patient, there has to be a good reason.”

And, he said, antibiotics are an approved treatment. Doctors are familiar with the drugs. The ethics board that had to approve the clinical trial suggested a small pilot study instead.

The trial was difficult to set up. The challenge was to get to patients before they were given antibiotics.

“We made friends with the hospital lab which did the C. difficile fecal testing,” Dr. Bretthauer said. The laboratory technicians agreed to alert the researchers to new C. difficile cases.

The researchers then rushed to the doctors and asked them to delay giving antibiotics until the patients were asked to enter the study.

The results of the study, Dr. Bretthauer said, “speak for themselves.” But not until a larger trial is completed will he have convincing results that could change clinical practice.

Dr. Khoruts said that in he will wait for the large clinical trial before using fecal transplants as a first-line therapy against C. difficile.

But “if you asked me what if my mother had it?” Then, he said, “I wouldn’t wait” to offer her a fecal transplant.

Trillions Upon Trillions of Viruses Fall From the Sky Each Day


Generally it’s assumed these viruses originate on the planet and are swept upward, but some researchers theorize that viruses actually may originate in the atmosphere. (There is a small group of researchers who believe viruses may even have come here from outer space, an idea known as panspermia.)

Whatever the case, viruses are the most abundant entities on the planet by far. While Dr. Suttle’s team found hundreds of millions of viruses in a square meter, they counted tens of millions of bacteria in the same space.

Mostly thought of as infectious agents, viruses are much more than that. It’s hard to overstate the central role that viruses play in the world: They’re essential to everything from our immune system to our gut microbiome, to the ecosystems on land and sea, to climate regulation and the evolution of all species. Viruses contain a vast diverse array of unknown genes — and spread them to other species.

Last year, three experts called for a new initiative to better understand viral ecology, especially as the planet changes. “Viruses modulate the function and evolution of all living things,” wrote Matthew B. Sullivan of Ohio State, Joshua Weitz of Georgia Tech, and Steven W. Wilhelm of the University of Tennessee. “But to what extent remains a mystery.”

Photo

Viruses reproduce by attaching to a bacterium and injecting their own genes. Ancient viral DNA eventually became part of the nervous system of modern humans, playing a roll in consciousness, nerve communication and memory formation.

Credit
Biozentrum, University of Basel/Science Source

Do viruses even fit the definition of something alive? While they are top predators of the microbial world, they lack the ability to reproduce and so must take over the cell of a host — called an infection — and use its machinery to replicate. The virus injects its own DNA into the host; sometimes that new genes are useful to the host and become part of its genome.

Researchers recently identified an ancient virus that inserted its DNA into the genomes of four-limbed animals that were human ancestors. That snippet of genetic code, called ARC, is part of the nervous system of modern humans and plays a role in human consciousness — nerve communication, memory formation and higher-order thinking. Between 40 percent and 80 percent of the human genome may be linked to ancient viral invasions.

Viruses and their prey are also big players in the world’s ecosystems. Much research now is aimed at factoring their processes into our understanding of how the planet works.

“If you could weigh all the living material in the oceans, 95 percent of it is stuff is you can’t see, and they are responsible for supplying half the oxygen on the planet,” Dr. Suttle said.

In laboratory experiments, he has filtered viruses out of seawater but left their prey, bacteria. When that happens, plankton in the water stop growing. That’s because when preying viruses infect and take out one species of microbe — they are very specific predators — they liberate nutrients in them, such as nitrogen, that feed other species of bacteria. In the same way, an elk killed by a wolf becomes food for ravens, coyotes and other species. As plankton grow, they take in carbon dioxide and create oxygen.

One study estimated that viruses in the ocean cause a trillion trillion infections every second, destroying some 20 percent of all bacterial cells in the sea daily.

Viruses help keep ecosystems in balance by changing the composition of microbial communities. As toxic algae blooms spread in the ocean, for example, they are brought to heel by a virus that attacks the algae and causes it to explode and die, ending the outbreak in as little as a day.

While some viruses and other organisms have evolved together and have achieved a kind of balance, an invasive virus can cause rapid, widespread changes and even lead to extinction.

West Nile virus has changed the composition of bird communities in much of the United States, killing crows and favoring ravens, some researchers say. Multiple extinctions of birds in Hawaii are predicted as the mosquito-borne avipoxvirus spreads into mountain forests where it was once too cold for mosquitoes to live.

When species disappear, the changes can ripple through an ecosystem. A textbook example is a viral disease called rinderpest.

Photo

An engraving showing a cattle inspection at a market in 19th century London, when rinderpest, a viral disease, was rampant in Europe and Africa, wiping out some herds entirely.

Credit
Universal History Archive/UIG, via Getty Images

The Italian army brought a few cattle into North Africa, and in 1887 the virus took off across the continent, killing a broad range of cloven-hoofed animals from Eritrea to South Africa — in some cases wiping out 95 percent of the herds.

“It infected antelope, it infected wildebeest and other large grazers across the whole ecosystem,” said Peter Daszak, the president of Ecohealth Alliance, which is working on a global project to catalog viruses likely to pass from animals to humans.

“The impact was not just on the animals. But because they are primary grazers and they died off in huge numbers, vegetation was impacted, and it allowed trees to grow where they would have been grazed away,” he said.

“The large acacia trees on the plains of Africa are all the same age and were seedlings when rinderpest first came in and the wildlife died,” Dr. Daszak said. In other places, far less grazing created a hospitable habitat for the tsetse fly, which carries the parasites that cause sleeping sickness.

“These kinds of ecological changes can last for centuries or even millennia,” Dr. Daszak said.

Combined with drought, large numbers of people died from starvation as rinderpest spread. An explorer in 1891 estimated two-thirds of the Masai people, who depended on cattle, were killed.

“Almost instantaneously, rinderpest swept away the wealth of tropical Africa,” wrote John Reader in his book “Africa: A Biography of a Continent.”

With intensive vaccinations, rinderpest was completely wiped out, not only in Africa but globally in 2011.

The beneficial effects of viruses are much less known, especially among plants. “There are huge questions in wild systems about what viruses are doing there,” said Marilyn Roossinck, who studies viral ecology in plants at Pennsylvania State University. “We have never found deleterious effects from a virus in the wild.”

A grass found in the high-temperature soils of Yellowstone’s geothermal areas, for example, needs a fungus to grow in the extreme environment. In turn, the fungus needs a virus.

Tiny spots of virus on the plant that yields quinoa is also important for the plant’s survival. “Little spots of virus confer drought tolerance but don’t cause disease,” she said. “It changes the whole plant physiology.”

“Viruses aren’t our enemies,” Dr. Suttle said. “Certain nasty viruses can make you sick, but it’s important to recognize that viruses and other microbes out there are absolutely integral for the ecosystem.”

Continue reading the main story

Trillions Upon Trillions of Viruses Fall From the Sky Each Day


Generally it’s assumed these viruses originate on the planet and are swept upward, but some researchers theorize that viruses actually may originate in the atmosphere. (There is a small group of researchers who believe viruses may even have come here from outer space, an idea known as panspermia.)

Whatever the case, viruses are the most abundant entities on the planet by far. While Dr. Suttle’s team found hundreds of millions of viruses in a square meter, they counted tens of millions of bacteria in the same space.

Mostly thought of as infectious agents, viruses are much more than that. It’s hard to overstate the central role that viruses play in the world: They’re essential to everything from our immune system to our gut microbiome, to the ecosystems on land and sea, to climate regulation and the evolution of all species. Viruses contain a vast diverse array of unknown genes — and spread them to other species.

Last year, three experts called for a new initiative to better understand viral ecology, especially as the planet changes. “Viruses modulate the function and evolution of all living things,” wrote Matthew B. Sullivan of Ohio State, Joshua Weitz of Georgia Tech, and Steven W. Wilhelm of the University of Tennessee. “But to what extent remains a mystery.”

Photo

Viruses reproduce by attaching to a bacterium and injecting their own genes. Ancient viral DNA eventually became part of the nervous system of modern humans, playing a roll in consciousness, nerve communication and memory formation.

Credit
Biozentrum, University of Basel/Science Source

Do viruses even fit the definition of something alive? While they are top predators of the microbial world, they lack the ability to reproduce and so must take over the cell of a host — called an infection — and use its machinery to replicate. The virus injects its own DNA into the host; sometimes that new genes are useful to the host and become part of its genome.

Researchers recently identified an ancient virus that inserted its DNA into the genomes of four-limbed animals that were human ancestors. That snippet of genetic code, called ARC, is part of the nervous system of modern humans and plays a role in human consciousness — nerve communication, memory formation and higher-order thinking. Between 40 percent and 80 percent of the human genome may be linked to ancient viral invasions.

Viruses and their prey are also big players in the world’s ecosystems. Much research now is aimed at factoring their processes into our understanding of how the planet works.

“If you could weigh all the living material in the oceans, 95 percent of it is stuff is you can’t see, and they are responsible for supplying half the oxygen on the planet,” Dr. Suttle said.

In laboratory experiments, he has filtered viruses out of seawater but left their prey, bacteria. When that happens, plankton in the water stop growing. That’s because when preying viruses infect and take out one species of microbe — they are very specific predators — they liberate nutrients in them, such as nitrogen, that feed other species of bacteria. In the same way, an elk killed by a wolf becomes food for ravens, coyotes and other species. As plankton grow, they take in carbon dioxide and create oxygen.

One study estimated that viruses in the ocean cause a trillion trillion infections every second, destroying some 20 percent of all bacterial cells in the sea daily.

Viruses help keep ecosystems in balance by changing the composition of microbial communities. As toxic algae blooms spread in the ocean, for example, they are brought to heel by a virus that attacks the algae and causes it to explode and die, ending the outbreak in as little as a day.

While some viruses and other organisms have evolved together and have achieved a kind of balance, an invasive virus can cause rapid, widespread changes and even lead to extinction.

West Nile virus has changed the composition of bird communities in much of the United States, killing crows and favoring ravens, some researchers say. Multiple extinctions of birds in Hawaii are predicted as the mosquito-borne avipoxvirus spreads into mountain forests where it was once too cold for mosquitoes to live.

When species disappear, the changes can ripple through an ecosystem. A textbook example is a viral disease called rinderpest.

Photo

An engraving showing a cattle inspection at a market in 19th century London, when rinderpest, a viral disease, was rampant in Europe and Africa, wiping out some herds entirely.

Credit
Universal History Archive/UIG, via Getty Images

The Italian army brought a few cattle into North Africa, and in 1887 the virus took off across the continent, killing a broad range of cloven-hoofed animals from Eritrea to South Africa — in some cases wiping out 95 percent of the herds.

“It infected antelope, it infected wildebeest and other large grazers across the whole ecosystem,” said Peter Daszak, the president of Ecohealth Alliance, which is working on a global project to catalog viruses likely to pass from animals to humans.

“The impact was not just on the animals. But because they are primary grazers and they died off in huge numbers, vegetation was impacted, and it allowed trees to grow where they would have been grazed away,” he said.

“The large acacia trees on the plains of Africa are all the same age and were seedlings when rinderpest first came in and the wildlife died,” Dr. Daszak said. In other places, far less grazing created a hospitable habitat for the tsetse fly, which carries the parasites that cause sleeping sickness.

“These kinds of ecological changes can last for centuries or even millennia,” Dr. Daszak said.

Combined with drought, large numbers of people died from starvation as rinderpest spread. An explorer in 1891 estimated two-thirds of the Masai people, who depended on cattle, were killed.

“Almost instantaneously, rinderpest swept away the wealth of tropical Africa,” wrote John Reader in his book “Africa: A Biography of a Continent.”

With intensive vaccinations, rinderpest was completely wiped out, not only in Africa but globally in 2011.

The beneficial effects of viruses are much less known, especially among plants. “There are huge questions in wild systems about what viruses are doing there,” said Marilyn Roossinck, who studies viral ecology in plants at Pennsylvania State University. “We have never found deleterious effects from a virus in the wild.”

A grass found in the high-temperature soils of Yellowstone’s geothermal areas, for example, needs a fungus to grow in the extreme environment. In turn, the fungus needs a virus.

Tiny spots of virus on the plant that yields quinoa is also important for the plant’s survival. “Little spots of virus confer drought tolerance but don’t cause disease,” she said. “It changes the whole plant physiology.”

“Viruses aren’t our enemies,” Dr. Suttle said. “Certain nasty viruses can make you sick, but it’s important to recognize that viruses and other microbes out there are absolutely integral for the ecosystem.”

Continue reading the main story