Legion of Little Helpers in the Gut Keeps Us Alive

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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 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 -- 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 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.

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.