Text 34910, 178 rader
Skriven 2010-02-17 13:09:44 av Sean Dennis (1:18/200)
Ärende: Why do people become lactose intolerant?
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Hello, All.

This subject has been approached many times in here and I read this article
today that was quite interesting and describes some interesting results doing
experiments with genetic manipulation:

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From:
http://online.wsj.com/article/SB10001424052748703562404575067264166151750.html

Why Do People Become Lactose-Intolerant?
Scientists Turn to DNA in an Attempt to Answer Why Adults Develop Trouble
Digesting Milk But Can Eat Ice Cream

By Shirley S. Wang

(See Corrections & Amplifications item below.)

Most of us drank milk every day when we were young without a problem. Then,
sometime in our teens or early 20s, we start to feel bloated or have discomfort
after consuming a lot of milk, typically two or more glasses at a time.

Scientists have discovered that most people develop some degree of lactose
intolerance as they get older. Why we lose this ability to break down lactose,
the key sugar found in milk, is a puzzle that researchers have been trying to
figure out. The National Institute of Child Health and Human Development, part
of the National Institutes of Health, will hold its first conference on the
topic next week.

It is unusual for people to lose the ability to digest a nutrient as they age.
But most people stop making large quantities of "lactase"â€öthe enzyme that
breaks down lactoseâ€öafter childhood, says Eric Sibley, an associate professor
of pediatrics at the Stanford University School of Medicine, who has been
studying why people develop lactose intolerance as they get older.

Most people continue to produce some lactase, but at much-diminished levels.
After they reach their individual threshold and can no longer break down
lactose, it passes intact through the intestine until it reaches the colon,
where it is finally fermented by the bacteria that reside there. As the
bacteria do their job, they produce gas as a byproduct, which causes discomfort
and pain as well as symptoms such as cramping and diarrhea.

-- Training the Bacteria

Some people, after diagnosing themselves, cut out regular consumption of
dairyâ€öwhich can potentially make symptoms worse when they do consume it. The
bacteria in the gut can become less efficient at processing lactose if they
aren't continually asked to do it. Conversely, people can train the bacteria to
tolerate more dairy if they consume it regularly.

By understanding which genes and proteins are responsible for turning off
lactase production, scientists are hoping they can then flip a genetic switch
to turn the system back onâ€öbut only in the intestine. The hope is one day to
be able to "program the intestine to take on the ability to maximally use
nutrients," says Dr. Sibley.

This type of complex localized gene therapy isn't likely to be used in
run-of-the-mill lactose-intolerant individuals, who can just watch the amount
of dairy that they consume or take enzyme supplements. Instead, says Dr.
Sibley, it could be used to treat children with serious digestive diseases,
such as short bowel syndrome, get the nutrients they need.

Dairy products that have gone through some processing, such as cheese and ice
cream, tend to have less lactose because the fermentation process breaks some
of it down. But those with an intolerance should keep an eye out for lactose
that has been added to products like cookies by reading the food label, says
Gilman Grave, acting director of the National Institute of Child Health and
Human Development's Center for Research for Mothers and Children.

A separate group of individuals have an allergic reaction to milk that isn't
related to lactose. Instead, they are allergic to a protein in cow's milk and
tend to have more blood in their stool and abdominal pain, instead of bloating.
The allergy typically fades after childhood.

For years, doctors thought that lactose intolerance primarily affected
individuals from certain parts of the world, such as Asia and Africa. But newer
evidence suggests the opposite is true. Most adults develop lactose
intolerance. Only a minorityâ€öthose descended from herding cultures in
northern Europe and parts of Africaâ€öhave a mutation that allows them continue
to break down lactose into adulthood. The misperception likely developed in
part because so many Americans are of northern European descent and have the
mutation.

"A lot of people are self-diagnosing themselves with being lactose-intolerant
just because they're a member of a certain ethnicity, and they may not be," Dr.
Grave says.

Dr. Sibley, who holds a doctorate in biochemistry and also is a pediatric
gastroenterologist at Lucile Packard Children's Hospital at Stanford, has spent
more than 15 years in the lab investigating genes and proteins that tell the
lactase system to shut down production.

To track whether the lactase gene is turned on or off, Dr. Sibley borrowed the
firefly's "luciferase" gene, which is responsible for lighting up the firefly's
tail. Light is emitted when the gene is turned on.

In the lab, Dr. Sibley and his colleagues take fragments of DNA from regions
they think are important to lactase production and graft them into the
luciferase gene. They then implant the combination gene into human intestine
cells in a dish and allow them to grow. If the DNA fragment indeed starts the
lactose production process, it turns the gene on. Thanks to the graft, the
turned-on gene emits light, which can be measured.

Using these methods, Dr. Sibley figured out what section of DNA appeared to be
responsible for turning the lactase system on and off. In cells from people
descended from northern Europeans, a single genetic mutation was associated
with the continued ability to tolerate lactose.

They then took cells with those mutations, and in a dish, showed that they
increased luceriferase production, which suggests the mutation does change the
cell's behavior. These findings were published in 2003 in the journal Human
Molecular Genetics.

With the small segment of the African population that is lactose-tolerant, the
mutations appear to be slightly different but are located in the same region of
the DNA.


--Multiple Proteins

Dr. Sibley and his colleagues have also identified several key proteins that
must be bound to specific regions of the lactase gene and in the right
combinations in order to turn on the gene. One protein they are currently
studying, called PDX-1, appears to suppress lactase production in cells in the
dish. But when the group generated mice that don't make PDX-1, lactase
production was only slightly increased. This suggests that there are multiple
proteins working together to suppress lactase and that PDX-1 alone isn't enough
to turn the system off completely, says Dr. Sibley.

They also are working to figure out which segment of the DNA sequence tells the
lactase gene to produce lactase in certain cells of the intestine but not
others, and when the system should be turned off. The ultimate goal of this
line of research would be to be able to turn on genes in cells in the intestine
that don't naturally produce it, says Dr. Sibley.

Individuals who are worried they are lactose-intolerant can do a self-test by
cutting out dairy for two weeks and seeing if their symptoms subside, says Dr.
Sibley. There is also a breathalyzer test that measures the amount of hydrogen
in the breath, which is a byproduct that bacteria produce if they are breaking
down lactose. Most individuals don't need it to be diagnosed with lactose
intolerance, according to Dr. Sibley.

For most individuals, lactose intolerance doesn't mean they should permanently
cut out all dairy. Studies have shown that people who are lactose intolerant
can drink one to two glasses of milk a day without symptoms, says Dr. Grave,
who encourages all people without allergies to drink this amount. Many people
say their symptoms actually improve when they regularly drink milk, perhaps
because the bacteria in the colon break down lactose more efficiently or the
number of bacteria build up, he says.

Another reason to drink milk: calcium. If children in particular don't get the
amount of calcium they need, their growth and skeletal health may be
compromised, says Dr. Grave. A New Zealand study showed that kids on a
dairy-free diet get only one-third of their needed daily calcium and had a
higher fracture rate, compared with kids who consumed dairy.

It is certainly possible to get calcium from other foods, but people would have
to eat vast amounts of it in order to get the same amount found in dairy, says
Dr. Grave. For instance, you would have to eat many servings of spinach in
order to absorb the same amount of calcium you would get in one cup of milk.

Write to Shirley S. Wang at shirley.wang@wsj.com

Corrections & Amplifications:

Eric Sibleyis an associate professor of pediatrics at the Stanford University
School of Medicine. Tuesday's In the Lab column on lactose intolerance
incorrectly identified him as an assistant professor.
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Later,
Sean

... The trick is to make sure you don't die waiting for prosperity to
come.-Iacocca

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