By CARL ZIMMER
Blood type, meet bug type.
“It’s an important advance,” said Rob Knight, a biologist at the University of Colorado, who was not involved in the research. “It’s the first indication that human gut ecosystems may fall into distinct types.”
The research team, led by Peer Bork of the European Molecular Biology Laboratory in Heidelberg, Germany, found no link between what they call enterotypes and the ethnic background of the European, American and Japanese subjects they studied.
Nor could they find a connection to sex, weight, health or age. They are now exploring other explanations. One possibility is that infants are randomly colonized by different pioneering species of gut microbes. The microbes alter the gut so that only certain species can follow them.
Whatever the cause of the different enterotypes, they may end up having discrete effects on people’s health. Gut microbes aid in food digestion and synthesize vitamins, using enzymes our own cells cannot make.
Dr. Bork and his colleagues have found that each of the types makes a unique balance of these enzymes. Enterotype 1 produces more enzymes for making vitamin B7 (also known as biotin), for example, and Enterotype 2 more enzymes for vitamin B1 (thiamine).
The discovery of the blood types A, B, AB and O had a major effect on how doctors practice medicine. They could limit the chances that a patient’s body would reject a blood transfusion by making sure the donated blood was of a matching type. The discovery of enterotypes could someday lead to medical applications of its own, but they would be far down the road.
“Some things are pretty obvious already,” Dr. Bork said. Doctors might be able to tailor diets or drug prescriptions to suit people’s enterotypes, for example.
Or, he speculated, doctors might be able to use enterotypes to find alternatives to antibiotics, which are becoming increasingly ineffective. Instead of trying to wipe out disease-causing bacteria that have disrupted the ecological balance of the gut, they could try to provide reinforcements for the good bacteria. “You’d try to restore the type you had before,” he said. Dr. Bork notes that more testing is necessary. Researchers will need to search for enterotypes in people from African, Chinese and other ethnic origins. He also notes that so far, all the subjects come from industrial nations, and thus eat similar foods. “This is a shortcoming,” he said. “We don’t have remote villages.”
The discovery of enterotypes follows on years of work mapping the diversity of microbes in the human body— the human microbiome, as it is known. The difficulty of the task has been staggering. Each person shelters about 100 trillion microbes. (For comparison, the human body is made up of only around 10 trillion cells.) But scientists cannot rear a vast majority of these bacteria in their labs to identify them and learn their characteristics.
As genetics developed, scientists learned how to study the microbiome by analyzing its DNA. Scientists extracted DNA fragments from people’s skin, saliva and stool. They learned how to recognize and discard human DNA, so that they were left with genes from the microbiome. They searched through the remaining DNA for all the variants of a specific gene and compared them with known species. In some cases, the variants proved to be from familiar bacteria, like E. coli. In other cases, the gene belonged to a species new to science.
These studies offered glimpses of a diversity akin to a rain forest’s. Different regions of the body were home to different combinations of species. From one person to another, scientists found more tremendous variety. Many of the species that lived in one person’s mouth, for example, were missing from another’s.
Scientists wondered if deeper studies would reveal a unity to human microbiomes. Over the past few years, researchers have identified the genomes — the complete catalog of genes — of hundreds of microbe species that live in humans. Now they can compare any gene they find with these reference genomes. They can identify the gene’s function, and identify which genus of bacteria the microbe belongs to. And by tallying all the genes they find, the scientists can estimate how abundant each type of bacteria is.
In the recent work, Dr. Bork and his team carried out an analysis of the gut microbes in 22 people from Denmark, France, Italy and Spain. Some of their subjects were healthy, while others were obese or suffered from intestinal disorders like Crohn’s disease. Dr. Bork and his colleagues searched for fragments of DNA corresponding to the genomes of 1,511 different species of bacteria. The researchers combined their results with previous studies of 13 Japanese individuals and four Americans.
The scientists then searched for patterns. “We didn’t have any hypothesis,” Dr. Bork said. “Anything that came out would be new.”
Still, Dr. Bork was startled by the result of the study: all the microbiomes fell neatly into three distinct groups.
And, as Dr. Bork and his colleagues reported on Wednesday in the journal Nature, each of the three enterotypes was composed of a different balance of species. People with type 1, for example, had high levels of bacteria called Bacteroides. In type 2, on the other hand, Bacteroides were relatively rare, while the genus Prevotella was unusually common.
“You can cut the data in lots of different ways, and you still get these three clusters,” Dr. Bork said.
Dr. Bork and his colleagues found confirmation of the three enterotypes when they turned to other microbiome surveys, and the groups continue to hold up now that they have expanded their own study to 400 people.
The research team, led by Peer Bork of the European Molecular Biology Laboratory in Heidelberg, Germany, found no link between what they call enterotypes and the ethnic background of the European, American and Japanese subjects they studied.
Nor could they find a connection to sex, weight, health or age. They are now exploring other explanations. One possibility is that infants are randomly colonized by different pioneering species of gut microbes. The microbes alter the gut so that only certain species can follow them.
Whatever the cause of the different enterotypes, they may end up having discrete effects on people’s health. Gut microbes aid in food digestion and synthesize vitamins, using enzymes our own cells cannot make.
Dr. Bork and his colleagues have found that each of the types makes a unique balance of these enzymes. Enterotype 1 produces more enzymes for making vitamin B7 (also known as biotin), for example, and Enterotype 2 more enzymes for vitamin B1 (thiamine).
The discovery of the blood types A, B, AB and O had a major effect on how doctors practice medicine. They could limit the chances that a patient’s body would reject a blood transfusion by making sure the donated blood was of a matching type. The discovery of enterotypes could someday lead to medical applications of its own, but they would be far down the road.
“Some things are pretty obvious already,” Dr. Bork said. Doctors might be able to tailor diets or drug prescriptions to suit people’s enterotypes, for example.
Or, he speculated, doctors might be able to use enterotypes to find alternatives to antibiotics, which are becoming increasingly ineffective. Instead of trying to wipe out disease-causing bacteria that have disrupted the ecological balance of the gut, they could try to provide reinforcements for the good bacteria. “You’d try to restore the type you had before,” he said. Dr. Bork notes that more testing is necessary. Researchers will need to search for enterotypes in people from African, Chinese and other ethnic origins. He also notes that so far, all the subjects come from industrial nations, and thus eat similar foods. “This is a shortcoming,” he said. “We don’t have remote villages.”
The discovery of enterotypes follows on years of work mapping the diversity of microbes in the human body— the human microbiome, as it is known. The difficulty of the task has been staggering. Each person shelters about 100 trillion microbes. (For comparison, the human body is made up of only around 10 trillion cells.) But scientists cannot rear a vast majority of these bacteria in their labs to identify them and learn their characteristics.
As genetics developed, scientists learned how to study the microbiome by analyzing its DNA. Scientists extracted DNA fragments from people’s skin, saliva and stool. They learned how to recognize and discard human DNA, so that they were left with genes from the microbiome. They searched through the remaining DNA for all the variants of a specific gene and compared them with known species. In some cases, the variants proved to be from familiar bacteria, like E. coli. In other cases, the gene belonged to a species new to science.
These studies offered glimpses of a diversity akin to a rain forest’s. Different regions of the body were home to different combinations of species. From one person to another, scientists found more tremendous variety. Many of the species that lived in one person’s mouth, for example, were missing from another’s.
Scientists wondered if deeper studies would reveal a unity to human microbiomes. Over the past few years, researchers have identified the genomes — the complete catalog of genes — of hundreds of microbe species that live in humans. Now they can compare any gene they find with these reference genomes. They can identify the gene’s function, and identify which genus of bacteria the microbe belongs to. And by tallying all the genes they find, the scientists can estimate how abundant each type of bacteria is.
In the recent work, Dr. Bork and his team carried out an analysis of the gut microbes in 22 people from Denmark, France, Italy and Spain. Some of their subjects were healthy, while others were obese or suffered from intestinal disorders like Crohn’s disease. Dr. Bork and his colleagues searched for fragments of DNA corresponding to the genomes of 1,511 different species of bacteria. The researchers combined their results with previous studies of 13 Japanese individuals and four Americans.
The scientists then searched for patterns. “We didn’t have any hypothesis,” Dr. Bork said. “Anything that came out would be new.”
Still, Dr. Bork was startled by the result of the study: all the microbiomes fell neatly into three distinct groups.
And, as Dr. Bork and his colleagues reported on Wednesday in the journal Nature, each of the three enterotypes was composed of a different balance of species. People with type 1, for example, had high levels of bacteria called Bacteroides. In type 2, on the other hand, Bacteroides were relatively rare, while the genus Prevotella was unusually common.
“You can cut the data in lots of different ways, and you still get these three clusters,” Dr. Bork said.
Dr. Bork and his colleagues found confirmation of the three enterotypes when they turned to other microbiome surveys, and the groups continue to hold up now that they have expanded their own study to 400 people.
This article has been revised to reflect the following correction:
Correction: April 20, 2011
Correction: April 20, 2011
An earlier version of this article misstated the number of microbes relative to the number of cells in the human body. Each person shelters about 100 trillion microbes, not 10 trillion, and is made up of about 10 trillion cells, not one million.
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