Celiac disease is an auto-immune disease in which a
person reacts to gluten - a protein found in grains including rye, wheat, barley
and also oats. It is estimated that about 1% of the American population has
celiac disease. Around 80% of Americans with celiac disease are undiagnosed or
misdiagnosed with other conditions.
When a person with celiac disease eats gluten, their immune
system produces antibodies against gluten which can also causing damage to the
small intestine. This leads to the symptoms of celiac disease including abdominal
pain, diarrhea, bloating, malnutrition and fatigue. The only existing
treatment for celiac disease is a gluten-free diet.
The answer to this has been uncertain, but recent study
suggests it may be explained by how specific gut bacteria respond to gluten. Some
researchers have proposed that the presence of specific gut bacteria may have a
role in the development of celiac disease.
Dr. Elena F. Verdu, of the Digestive Health Research
Institute at McMaster University in Canada, and her colleagues have
investigated how the immune responses to gluten varies with different
populations of gut bacteria in mouse models with gluten intolerance. Their
findings were published in The American Journal of Pathology.
The team assessed three groups of mice that expressed a gene
called DQ8, which is also found in humans and makes them genetically
susceptible to gluten intolerance. Each group of mice had different gut
bacteria compositions, or gut microbiomes. The researchers exposed each group
of mice to the same amount of gluten.
- Group 1 mice were germ free
- Group 2 mice had specific, pathogen-free flora which possessed a wide range of normal gut bacteria; their gut microbiomes were free of Proteobacteria; and did not have any opportunistic pathogens present
- Group 3 mice, also had specific, pathogen-free flora (as for group 2), but it also included Proteobacteria such as Escherichia coli and Helicobacter; and also included other opportunistic pathogens such as Staphylococcus and Streptococcus
Note:
- Opportunistic pathogens are bacteria which live normally on/in the body and cause disease in people with a compromised immune system or other pre-existing disease.
Gram negative bacilli
. Results: Group 1 – The Germ Free Mice
The germ- free mice exhibited signs of celiac disease. The
germ-free mice showed increased levels of intraepithelial lymphocytes in the
gut. The proliferation and activation of intraepithelial lymphocytes is an
early indicator of celiac disease. The germ-free mice also experienced
increased death of cells called enterocytes that line the gastrointestinal
tract, as well as anatomical alterations of the villi, the small, finger-like
projections that line the small intestine.
The researchers also identified that the germ free mice in
group 1 developed antibodies in response to gliadin, a component of gluten. These
mice also demonstrated T-cell responses specific to this component.
Results: Groups 1 mice with specific, pathogen-free flora
Increased intraepithelial lymphocytes levels were not seen
in group 2, the mice with specific, pathogen-free flora only
Results: Groups 2 mice with specific, pathogen-free flora, Proteobacteria and opportunistic pathogens
The group 3 mice demonstrated greater gluten-induced
pathology than the group 2 mice, according to the researchers, so the team set
out to investigate whether the presence of Proteobacteria,
such as Escherichia and Helicobacter, plays a role.
The team found that development of gluten-induced pathology
was NOT halted if the mice were also inoculated with entero-adherent Escherichia coli isolated from a
patient with celiac disease.
They found that the presence of Proteobacteria worsened gluten-induced pathology. On increasing the
presence of Proteobacteria in new
born mice, the researchers found that gluten-induced pathology got worse.
Specifically, the team identified an increase in levels of intraepithelial
lymphocytes.
Conclusions
"These studies demonstrate that perturbation of early
microbial colonization in life and induction of dysbiosis (microbial imbalance
inside the body), characterized by increased Proteobacteria, enhances the severity of gluten-induced responses
in mice genetically predisposed to gluten sensitivity," says Dr. Verdu. "Importantly,
our data argue that the recognized increase in celiac disease prevalence in the
general population over the last 50 years could be driven, at least in part, by
perturbations in intestinal microbial ecology. Specific microbiota-based
therapies may aid in the prevention or treatment of celiac disease in subjects
with moderate genetic risk."
In an editorial linked to the study, Dr. Robin G. Lorenz, of
the University of Alabama at Birmingham, notes that while these findings
suggest the presence of Proteobacteria
may play an important role in celiac disease pathology, they do not mean that Proteobacteria causes the condition. An
alternative, he suggests, is that Proteobacteria
somehow boost the immune response to gluten or gliadin.