Wednesday, February 13, 2008
Life

Your Inner Life: Science is starting to explore the life and use of
the trillions of microbes that live inside us

By David Steinkraus
Journal Times
Wednesday, February 13, 2008 2:11 AM CST

There is a world within us that is not spiritual yet is intimately
connected to our well being. It is a mysterious world, known but
unexplored, and scheduled to be explored over the next several years
by scientists curious about the link between you, the world within and
your health.

This world is more you than you are, at least as counted by numbers.
Of all the cells that you consider to be yourself, only some 10
percent are human. The rest, 10 to 100 trillion, are something else —
microbes of one kind or another that live on your skin, in your ears
and throat, and in your intestine.

Mostly these organisms live quietly, but without many you couldn’t
live. Some synthesize vitamins. Others digest substances you cannot,
such as the cellulose that comprises the cell walls of plants.
Experiments in mice have demonstrated that without the presence of
bacteria, the mammalian intestine doesn’t develop properly. And when
this internal ecosystem is thrown out of balance you can become as
unhealthy as a lawn full of weeds.

At least that’s the current hypothesis about the thousand or so
microbe species thought to live in and on you. It is the reason why
the National Institutes of Health is committing about $113 million
over the next five years to try and figure out what lives with us and
how it affects our health.

The project is an outgrowth of the human genome project in which
scientists broke genes apart and figured out the order of every
nucleic acid, the building blocks of DNA. Their ambition this time is
no less: to feed samples of our microflora (the term for the
microorganisms specific to a place, in this case us) into machines
that will split their genomes apart. What they want to figure out is
the composition of our microbiome, our interrelated groups and species
of microbes.

Although sequencing the human genome sequence, the pace of the work
changed as the project progressed and has changed since, said Dr. Alan
Krensky, a deputy director of NIH and director of the office of
portfolio analysis and strategic initiatives.

“And so now sequencing is very affordable. They can do large amounts.
It’s all robots and computers and the like,” he said. “You take all
these different sequences together and the computers will figure out
that there are really 200 organisms there. It will take the pieces and
connect them.”

For years microbiologists have been hampered by an inability to grow
many of these organisms in a laboratory, Krensky said. Scientists
can’t create the right conditions. And the reason why this is so
important is the hint that we already have about how intimately the
organisms inside us can affect our health.

Tiny clues

About two years ago, a group of researchers at Washington University
in St. Louis reported that the composition of intestinal microflora in
mice was related to whether humans were obese. They found that the
composition of microflora changed as people lost weight, and when they
examined what these organisms did in mice, they found that the
microbiome of obese mice more broke food down more completely thus
releasing more calories for the mice to use. Yet what influences what,
whether the bacteria cause obesity or are a reaction to it, is not
clear.

There is also evidence that bacteria in the intestine can change the
body. A Swiss-British team, based in part at the Nestle Research
Center in Switzerland, found that people who desired chocolate and
those who didn’t may be influenced in part by how their diets affect
microbial activity in their digestive tracts.

Much of this work, this realization that microbes are so numerous and
are more diverse than we thought is the realization of only about the
last 10 years, said Hank Seifert, professor and associate chair of the
Department of Microbiology-Immunology at Northwestern University’s
Feinberg School of Medicine in Chicago. “A lot of this work started
with people probing what existed in the environment.” They looked in
mines and oceans, found unknown microbes, and then looked at the human
body, primarily the gut, he said, “and they said, ‘Wow, there’s a lot
more microbes than we realized.’ ”

“We always thought that ulcer disease was stress and eating the wrong
foods,” Krensky said. “When I started medical school that’s what they
taught us. But a group of researchers in Australia found that it’s a
bacteria (H. pylori) that causes it. So now you get antibiotics, and
your ulcer disappears. It’s pretty extraordinary. That’s the kind of
thing that may happen in other diseases.”

The first year of the project will be for sequencing, he said. For him
the second year will bring the most excitement because then
researchers will be invited to demonstrate how to apply the sequencing
knowledge.

Right in the gut

When one looks at the Western world, there is a disproportionate
amount of cancer and chronic inflammation, said Dr. David Binion. He
is a professor of gastroenterology and hepatoloty at the Medical
College of Wisconsin and directs the inflammatory bowel disease
center. He suffers from Crohn’s disease himself, which gives him a
very personal interest in the NIH project.

Problems with colon cancer do not occur in areas where the diet
contains a large amount of fiber, he said. “Now we have to remember
that humans have evolved over thousands and thousands of year, and the
way we live in Wisconsin in the year 2008 doesn’t bear much
resemblance to the way we have developed.”

Typical of that are less developed parts of the world where sanitation
is poorer and the number of bacteria people are exposed to is much
greater. That suggests that the microflora of Third World environments
is probably very different than microflora found in First World
people. So it’s reasonable to assume, he said, that such changes in
the microflora could change the health of people in developed nations.

The link with IBD (inflammatory bowel disease), Binion said, is that
researchers suspect it is due to inflammation that results from an
inappropriate reaction of the gut to bacteria.

The gut is the body’s largest mucosal surface (about equal to a double
tennis court if it’s flattened out) and one of its important immune
barriers, said Dr. Nita Salzman, a researcher at the medical college
who specializes in the antimicrobial chemicals produced in the
intestine.

Yet the barrier is so tenuous, she said. Just a single layer of cells
separates the body from the inside of the intestine, which is really a
tube running through the middle of your body and connected to the
outside world. On top of that cell layer is a layer of mucous, and
many bacteria are content to live peacefully there, she said.

They multiply, and by taking up space they become part of the barrier
and allow no place for a pathogen to attach. They do more. They use up
the available food, thus reducing the supply for any pathogen which
tries to set up a colony, and they produce their own antibiotics to
kill off other bacteria competing for that food and living space.

In Crohn’s disease, gut cells produce fewer of those antimicrobial
chemicals, Salzman said. The common hypothesis about the disease now
says that the number and kind of bacteria growing in the gut changes,
and that these microbes move through the mucous and trigger an immune
response from the intestinal cells.

It’s called a leaky gut, meaning the intestinal walls aren’t as
resistant as usual to letting substances through. There are hints that
it may be somehow involved with autism; children with that disorder
are known for digestive tract problems.

Leaky gut is seen in patients with IBD but also in the relatives of
people with IBD, Salzman said, which means the disease must come from
a leaky gut combined with some other factor.

Many questions

The medical college is hoping to put together a team for one of those
NIH grants, Salzman said. She also studies pediatric problems, and
children present particularly fertile ground for asking important
questions about the gut microbiome, how it forms, and how important it
is.

“The simple questions that we have: Is there such a thing as a healthy
microbiome. It seems that there’s quite a bit of variation, normal
variation, from person to person, but that each individual’s
colonization seems basically fixed over time.”

Then there are the rest of the questions: How much is a child’s
microflora like her mother’s? If the mother is treated with
antibiotics, what happens to the child’s microflora? What is the
effect of breast feeding versus formula feeding? Does the microbiome
affect the development of food allergies? And what matters, which
bacterial species dominates in the gut, or the mix of particular
species? “These are simple questions that are very hard to answer
because of the complexity of the system.”

Seifert, the microbiologist from Northwestern, studies Neisseria
gonorrhoeae, the organism which causes gonorrhea in humans. It also
has cousins which live commonly and very peacefully in your nasal and
throat cavities.

“We have several Neisseria gonorrhoeae, and what’s lagging, of course,
are the normal flora relatives which is what you really need to
understand it. And that’s why the microbiome thing is so exciting,
because we’re realizing that just understanding the frank pathogens is
not enough. You need to understand all the ecosystem.”

Journal Times
Copyright © 2008 -

Article Link:
http://www.journaltimes.com/articles/2008/02/13/life/doc47b22dfa88dfa733751402.txt