GUT BACTERIA THAT PROTECT AGAINST FOOD ALLERGIES
The presence of
Clostridia, a common class of gut bacteria, protects against food allergies, a
new study in mice finds. By inducing immune responses that prevent food
allergens from entering the bloodstream, Clostridia minimize allergen exposure
and prevent sensitization -- a key step in the development of food allergies.
The discovery points toward probiotic therapies for this so-far untreatable
condition, report scientists from the University of Chicago, Aug 25 in the Proceedings
of the National Academy of Sciences
Although the causes of
food allergy -- a sometimes deadly immune response to certain foods -- are
unknown, studies have hinted that modern hygienic or dietary practices may play
a role by disturbing the body's natural bacterial composition. In recent years,
food allergy rates among children have risen sharply -- increasing
approximately 50 percent between 1997 and 2011 -- and studies have shown a
correlation to antibiotic and antimicrobial use.
"Environmental
stimuli such as antibiotic overuse, high fat diets, caesarean birth, removal of
common pathogens and even formula feeding have affected the microbiota with
which we've co-evolved," said study senior author Cathryn Nagler, PhD, Bunning
Food Allergy Professor at the University of Chicago. "Our results suggest
this could contribute to the increasing susceptibility to food allergies."
To test how gut
bacteria affect food allergies, Nagler and her team investigated the response
to food allergens in mice. They exposed germ-free mice (born and raised in
sterile conditions to have no resident microorganisms) and mice treated with
antibiotics as newborns (which significantly reduces gut bacteria) to peanut
allergens. Both groups of mice displayed a strong immunological response,
producing significantly higher levels of antibodies against peanut allergens
than mice with normal gut bacteria.
This sensitization to
food allergens could be reversed, however, by reintroducing a mix of Clostridia
bacteria back into the mice. Reintroduction of another major group of
intestinal bacteria, Bacteroides, failed to alleviate sensitization, indicating
that Clostridia have a unique, protective role against food allergens.
Closing the door
To identify this
protective mechanism, Nagler and her team studied cellular and molecular immune
responses to bacteria in the gut. Genetic analysis revealed that Clostridia
caused innate immune cells to produce high levels of interleukin-22 (IL-22), a
signaling molecule known to decrease the permeability of the intestinal lining.
Antibiotic-treated
mice were either given IL-22 or were colonized with Clostridia. When exposed to
peanut allergens, mice in both conditions showed reduced allergen levels in
their blood, compared to controls. Allergen levels significantly increased,
however, after the mice were given antibodies that neutralized IL-22,
indicating that Clostridia-induced IL-22 prevents allergens from entering the
bloodstream.
"We've identified
a bacterial population that protects against food allergen sensitization,"
Nagler said. "The first step in getting sensitized to a food allergen is
for it to get into your blood and be presented to your immune system. The
presence of these bacteria regulates that process." She cautions, however,
that these findings likely apply at a population level, and that the
cause-and-effect relationship in individuals requires further study.
While complex and
largely undetermined factors such as genetics greatly affect whether
individuals develop food allergies and how they manifest, the identification of
a bacteria-induced barrier-protective response represents a new paradigm for
preventing sensitization to food. Clostridia bacteria are common in humans and
represent a clear target for potential therapeutics that prevent or treat food
allergies. Nagler and her team are working to develop and test compositions
that could be used for probiotic therapy and have filed a provisional patent.
"It's exciting
because we know what the bacteria are; we have a way to intervene," Nagler
said. "There are of course no guarantees, but this is absolutely testable
as a therapeutic against a disease for which there's nothing. As a mom, I can
imagine how frightening it must be to worry every time your child takes a bite
of food."
"Food allergies
affect 15 million Americans, including one in 13 children, who live with this
potentially life-threatening disease that currently has no cure," said
Mary Jane Marchisotto, senior vice president of research at Food Allergy Research
& Education. "We have been pleased to support the research that has
been conducted by Dr. Nagler and her colleagues at the University of
Chicago."
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