Your Inner Life(Microbiology)

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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. "

 

 

 

 

 

 

Article Link:

http://www.journaltimes.com/articles/2008/02/13/life/doc47b22dfa88dfa7

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