*Legion of Little Helpers in the Gut Keeps Us Alive*

[Guest guest]

This is fascinating!

Keen

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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

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AR2006060400603.html

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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 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 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 --

andconvert 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 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 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.

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 contributed to this report./

© 2006 The Washington Post Company

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