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Legion of Little Helpers in the Gut Keeps Us Alive
By Rick Weiss
Washington Post Staff Writer
Monday, June 5, 2006; A06
So you think you are the self-reliant type.
A rugged individualist.
Well, give it up. You'd be nothing without the trillions of microbial minions toiling in your large intestine, performing crucial physiological functions that your highfalutin human cells wouldn't have a clue how to do.
That's one of the humbling truths emerging from the most thorough census yet of the bacterial tenants homesteading in our bodies. The new view, made possible by cutting-edge DNA screening methods, shows that the vaunted human genome -- all the genes in our cells -- is but a fraction of what it takes to make a human.
In fact, it's time to stop thinking of yourself as a single living thing at all, say the scientists behind the new work. Better to see yourself as a "super-organism," they say: a hybrid creature consisting of about 10 percent human cells and 90 percent bacterial cells.
"The numbers might strike fear into people, but the overall concept is one we have to understand and adjust to," said Steven Gill, a microbial geneticist who helped lead the study at the Institute for Genomic Research in Rockville.
A better understanding of the bacteria colonizing our bodies could have far-reaching medical implications. In the not-too-distant future, Gill and others predicted, doctors will test for subtle changes in the numbers and kinds of microbes in people's guts as early indicators of disease. Doctors may prescribe live bacterial supplements to bring certain physiological measures back into normal range. And drug companies will invent compounds that mimic or amplify the actions of helpful bacteria.
"These microbes are master physiological chemists," said Jeffrey I. Gordon of Washington University in St. Louis, another team member. "Understanding their biosynthetic capabilities and following the pathways by which they operate could be the starting point for a 21st-century pharmacopoeia."
Scientists have long recognized that the number of human cells in the body is dwarfed by the 100 trillion or so bacteria living in and on it. It's a daunting reality obscured by the fact that human cells are much bigger than bacterial cells. For all their numbers, bacteria account for only about three pounds of the average person's weight.
Just how important those three pounds are, however, has been difficult to appreciate until now. Most bacteria are too finicky to grow in laboratory dishes. As a result, little was known about who these majority shareholders really are and what, exactly, they are doing to and for us.
The new study, described in last week's issue of the journal Science, took a novel approach. Rather than struggling to grow the body's myriad microbes and testing their ability to perform various biochemical reactions -- the methods scientists traditionally use to classify bacteria -- the team used tiny molecular probes resembling DNA Velcro to retrieve tens of thousands of snippets of bacterial DNA from smidgeons of the intestinal output of two volunteers.
By comparing the DNA sequences of those snippets with those of previously studied bacteria, the team was able to sort many of the invisible bugs into known families.
Hundreds of others, it became clear, belong to microbial families unknown to science until now.
But the team members went further. By comparing the genetic puzzle pieces with similar sequences stored in databases, they were able to determine what biological functions many of these microbes are performing in the gut. And, as it turns out, no small number of those functions are crucial to human survival.
Some of the bacteria have the genetic machinery to make essential vitamins that are not found in the diet and that human cells can barely manufacture, including several B vitamins. Others make enzymes that can break the chemical bonds in plant fibers, or polysaccharides, where a plant's nutritional energy is stored.
"We have very few of those linkage-busting enzymes encoded in our own genome, but these microbial genomes have a whole arsenal of gene products to degrade plant polysaccharides to energy," Gordon said.
Some bacteria in the gut break down flavonoids and other chemicals made by plants that could cause cancer or other illnesses if they were not neutralized in the intestines.
Others have the genetic capacity to scavenge hydrogen gas from the gut -- a byproduct of digestion that can kill helpful bacteria -- and convert it into methane. That makes the intestines a more biologically friendly place, while contributing in sometimes embarrassing moments to Earth's accumulation of greenhouse gases.
And in one especially touching example, bacteria in the gut make generous quantities of an enzyme that facilitates the production of butyryl coenzyme A, a fatty acid that is a favorite food of the cells that line the colon.
"We provide them a great place to live," study author David A. Relman of Stanford University said of the bacterial cells, "and they are feeding the lining of our gut."
The new work does not purport to be a complete survey of all microbes in the human gut. And it did not even take a stab at the body's other pockets of microbial diversity -- primarily the nose and mouth, the vagina, and the skin. But it demonstrates that the DNA-based approach has the potential to reveal at last the metabolic details of our many mini-mes, said Claire M. Fraser-Liggett, president and director of the Institute for Genomic Research.
With the technology improving and getting cheaper, she said, it won't be long before it is easy to monitor a person's microbial changes from day to day -- or compare bacterial population structures among individuals who have different diets or health histories.
"One question we need to tackle is: Is there such a thing as a core microbiome, a set of organisms or bacterial genes you find in most or all individuals?" Fraser-Liggett said. "It may be that microbes are very stable and diet doesn't play a huge role. Or it may be that this is a snapshot in time reflecting something they ate in their last meal."
With that kind of information in hand, doctors could think about prescribing particular "probiotic" foods or supplements to change a patient's microbiome in healthful ways, or adjusting a patient's diet to make a better fit with the bugs that the patient is saddled with.
"To ignore our microbial side would be to ignore an important contributor to our health and our biology," Gordon said.
Edward DeLong, a professor at the Massachusetts Institute of Technology who has used similar techniques to study marine microbial diversity, said he was not completely comfortable with the idea that people are super-organisms. "I'm not sure where the super-organism ends and the environment begins," he said.
But he said he appreciated the focus on the positive side of bacteria.
"We typically think of microbes as being associated with human disease," DeLong said. "But they are always with us and are associated most of the time with human health."
Researcher Meg Smith contributed to this report.
By Rick Weiss
Washington Post Staff Writer
Monday, June 5, 2006; A06
So you think you are the self-reliant type.
A rugged individualist.
Well, give it up. You'd be nothing without the trillions of microbial minions toiling in your large intestine, performing crucial physiological functions that your highfalutin human cells wouldn't have a clue how to do.
That's one of the humbling truths emerging from the most thorough census yet of the bacterial tenants homesteading in our bodies. The new view, made possible by cutting-edge DNA screening methods, shows that the vaunted human genome -- all the genes in our cells -- is but a fraction of what it takes to make a human.
In fact, it's time to stop thinking of yourself as a single living thing at all, say the scientists behind the new work. Better to see yourself as a "super-organism," they say: a hybrid creature consisting of about 10 percent human cells and 90 percent bacterial cells.
"The numbers might strike fear into people, but the overall concept is one we have to understand and adjust to," said Steven Gill, a microbial geneticist who helped lead the study at the Institute for Genomic Research in Rockville.
A better understanding of the bacteria colonizing our bodies could have far-reaching medical implications. In the not-too-distant future, Gill and others predicted, doctors will test for subtle changes in the numbers and kinds of microbes in people's guts as early indicators of disease. Doctors may prescribe live bacterial supplements to bring certain physiological measures back into normal range. And drug companies will invent compounds that mimic or amplify the actions of helpful bacteria.
"These microbes are master physiological chemists," said Jeffrey I. Gordon of Washington University in St. Louis, another team member. "Understanding their biosynthetic capabilities and following the pathways by which they operate could be the starting point for a 21st-century pharmacopoeia."
Scientists have long recognized that the number of human cells in the body is dwarfed by the 100 trillion or so bacteria living in and on it. It's a daunting reality obscured by the fact that human cells are much bigger than bacterial cells. For all their numbers, bacteria account for only about three pounds of the average person's weight.
Just how important those three pounds are, however, has been difficult to appreciate until now. Most bacteria are too finicky to grow in laboratory dishes. As a result, little was known about who these majority shareholders really are and what, exactly, they are doing to and for us.
The new study, described in last week's issue of the journal Science, took a novel approach. Rather than struggling to grow the body's myriad microbes and testing their ability to perform various biochemical reactions -- the methods scientists traditionally use to classify bacteria -- the team used tiny molecular probes resembling DNA Velcro to retrieve tens of thousands of snippets of bacterial DNA from smidgeons of the intestinal output of two volunteers.
By comparing the DNA sequences of those snippets with those of previously studied bacteria, the team was able to sort many of the invisible bugs into known families.
Hundreds of others, it became clear, belong to microbial families unknown to science until now.
But the team members went further. By comparing the genetic puzzle pieces with similar sequences stored in databases, they were able to determine what biological functions many of these microbes are performing in the gut. And, as it turns out, no small number of those functions are crucial to human survival.
Some of the bacteria have the genetic machinery to make essential vitamins that are not found in the diet and that human cells can barely manufacture, including several B vitamins. Others make enzymes that can break the chemical bonds in plant fibers, or polysaccharides, where a plant's nutritional energy is stored.
"We have very few of those linkage-busting enzymes encoded in our own genome, but these microbial genomes have a whole arsenal of gene products to degrade plant polysaccharides to energy," Gordon said.
Some bacteria in the gut break down flavonoids and other chemicals made by plants that could cause cancer or other illnesses if they were not neutralized in the intestines.
Others have the genetic capacity to scavenge hydrogen gas from the gut -- a byproduct of digestion that can kill helpful bacteria -- and convert it into methane. That makes the intestines a more biologically friendly place, while contributing in sometimes embarrassing moments to Earth's accumulation of greenhouse gases.
And in one especially touching example, bacteria in the gut make generous quantities of an enzyme that facilitates the production of butyryl coenzyme A, a fatty acid that is a favorite food of the cells that line the colon.
"We provide them a great place to live," study author David A. Relman of Stanford University said of the bacterial cells, "and they are feeding the lining of our gut."
The new work does not purport to be a complete survey of all microbes in the human gut. And it did not even take a stab at the body's other pockets of microbial diversity -- primarily the nose and mouth, the vagina, and the skin. But it demonstrates that the DNA-based approach has the potential to reveal at last the metabolic details of our many mini-mes, said Claire M. Fraser-Liggett, president and director of the Institute for Genomic Research.
With the technology improving and getting cheaper, she said, it won't be long before it is easy to monitor a person's microbial changes from day to day -- or compare bacterial population structures among individuals who have different diets or health histories.
"One question we need to tackle is: Is there such a thing as a core microbiome, a set of organisms or bacterial genes you find in most or all individuals?" Fraser-Liggett said. "It may be that microbes are very stable and diet doesn't play a huge role. Or it may be that this is a snapshot in time reflecting something they ate in their last meal."
With that kind of information in hand, doctors could think about prescribing particular "probiotic" foods or supplements to change a patient's microbiome in healthful ways, or adjusting a patient's diet to make a better fit with the bugs that the patient is saddled with.
"To ignore our microbial side would be to ignore an important contributor to our health and our biology," Gordon said.
Edward DeLong, a professor at the Massachusetts Institute of Technology who has used similar techniques to study marine microbial diversity, said he was not completely comfortable with the idea that people are super-organisms. "I'm not sure where the super-organism ends and the environment begins," he said.
But he said he appreciated the focus on the positive side of bacteria.
"We typically think of microbes as being associated with human disease," DeLong said. "But they are always with us and are associated most of the time with human health."
Researcher Meg Smith contributed to this report.
