Embargoed until 2 p.m. EDT
NSF PR 02-77 - September 26, 2002
Researchers Find Trigger for Devastating Digestive
Disease, Propose Treatment
1. Wheat-based foods
are broken down in the stomach and the
upper part of the small intestine called
the duodenum. Gluten is broken down in
2. Some of the partially
digested food travels to the next segment
of the small intestine called the jejunum.
3. In the jejunum, structures
called villi with surface-bound enzymes
break food down into complex molecules
the body absorbs.
4. Gluten adheres to
the tips of villi where enzymes break
it down into simpler molecules called
peptides. Some of the peptides, called
33-MER, cannot be broken down any further.
This is true for all persons whether they
suffer from celiac sprue or not.
5. Absorption cells in
the gut lumen absorb 33-MER peptides and
pass them into the tissues of the lamina
propria. Antigen presenting cells (APC),
part of the body's immune system, target
foreign substances in the body for response
by the immune system. APC do this by binding
with the foreign substance, and then send
biochemical signals to white blood cells
to attack. In nearly all people with celiac
sprue, APC bind with 33-MER only if the
APC carry a protien called DQ2.
6. Once the intestinal
wall absorbs 33-MER peptides, APC in celiac
sprue patients signal white blood cells
to attack. The result is eventual desctruction
of absorption cells and villi in the intestinal
Credit: Kirk Woellert, National Science Foundation
Editors: High resolution
images are available for downloading at:
Video available upon request:
Contact Dena Headlee, email@example.com,
Researchers have found a peptide molecule that triggers
celiac sprue - a severe inflammation of the intestine
that results from eating wheat and related grains
- and propose a treatment strategy that relies on
bacterial enzymes to break down the offending molecule
in the digestive tract. As many as 1 in every 200
Americans suffers from the condition.
In the September 27 issue of Science, Chaitan
Khosla and his coworkers at Stanford University and
the University of Norway in Oslo, report disassembling
the large, complex mixture of gluten proteins and
identifying a single component that triggers the autoimmune
response characteristic of celiac sprue.
The study presents, "a combined chemical-physiological-immunological
answer to the question 'why is gluten toxic to a person
with celiac sprue?,'" said Khosla, whose work is supported
by the National Science Foundation (NSF). "If proven
correct, the findings will lead to new insights into
the causes of celiac sprue, and perhaps certain other
types of autoimmune diseases."
The researchers determined that the autoimmune response
in people with celiac sprue can be traced to an unusually
long molecule - a chain of 33 amino acids - that cannot
be broken down by the human digestive system. They
immersed the 33-amino acid chain in digestive enzymes
derived from bacteria and found that a bacterial enzyme,
prolyl endopeptidase, can break the chain into apparently
"The technology used to isolate and identify the peptide
trigger for celiac sprue, and the enzymology used
to neutralize the disease, are marvelous examples
of how research into the fundamental understanding
of life processes can directly influence human health,"
said Fred Heineken, program director in NSF's Biochemical
Celiac sprue is often diagnosed only after years of
painful symptoms. Presently, there is no cure. The
only treatment is to completely avoid grains that
contain gluten, such as wheat, rye and barley.
The disease usually surfaces in early childhood when
intestinal tissue begins to show signs of devastation.
Symptoms include chronic diarrhea and an inability
to gain weight or grow normally. When the disease
arises in adulthood, symptoms can also include fatigue,
weight loss, anemia and neurological symptoms. Over
time, celiac sprue can lead to overall sickness and
even intestinal cancer.
In the small intestine, enzymes from the pancreas initially
digest gluten by breaking it into a number of fragments
called peptides. In most people, the larger peptides
probably work their way down to the lower intestine
where they are eaten by microorganisms.
"But in people with celiac sprue, the stable 33-amino
acid peptide causes big problems because the molecule
is recognized as being a threat to the person's immune
system," said Khosla, who also received NSF's Alan
T. Waterman Award in 1999. On learning that his family
was faced with the illness, Khosla used the award
to pursue research on the disease.
Khosla and his coworkers believe the bacterial enzymes,
which worked in human tissue cultures as well as intact
rats, may result in a simple, oral supplement that
can eliminate the harmful effects of gluten. The treatment
approach would be similar to enzyme supplements taken
orally by people who cannot digest lactose, a sugar
found in milk.
Khosla adds that an approved therapy could be as many
as 5 to 8 years away, although research is already
underway and the treatment should be testable in people
within 2 to 3 years.
Note to broadcasters: b-roll is available of an interview
with Chaitan Khosla; Khosla in his laboratory; and
an interview with a woman and her 6-year-old son,
who discuss the challenges of living with celiac sprue.
Video available upon request: Contact Dena Headlee,
For a static illustration series of the disease process,
For more information on Celiac Sprue, see: http://www.nlm.nih.gov/medlineplus/celiacdisease.html
For more information on the Alan T. Waterman Award,