- August 27, 2014 at 5:09 am #120881
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A class of bacteria commonly found in the guts of people—and rodents—appears to keep mice safe from food allergies, a study suggests. The same bacteria are among those reduced by antibiotic use in early childhood. The research fits neatly into an emerging paradigm that helps explain a recent alarming increase in food allergies and other conditions, such as obesity and autoimmune disease, and hints at strategies to reverse the trend.
Food allergies have increased about 50% in children since 1997. There are various theories explaining why. One is that the 21st century lifestyle, which includes a diet very different from our ancestors’, lots of antibiotic use, and even a rise in cesarean section deliveries, has profoundly changed the makeup of microbes in the gut of many people in developed countries. For example, the average child in the United States has taken three courses of antibiotics by the time he or she is 2 years old, says Martin Blaser, an infectious disease specialist and microbiologist at New York University in New York City. (See here for more on the reach of microbiome research these days.)
Cathryn Nagler, an immunologist at the University of Chicago in Illinois, has spent years probing links between the immune system, intestinal bacteria, and the onset of allergies. Back in 2004, she and her colleagues reported that wiping out gut bacteria in mice led to food allergies. Since then, Nagler has continued trying to understand which bacteria offer allergy protection and how they accomplish that.
In one of the latest efforts, Nagler’s team first confirmed that mice given antibiotics early in life were far more susceptible to peanut sensitization, a model of human peanut allergy. Then, they introduced a solution containing Clostridia, a common class of bacteria that’s naturally found in the mammalian gut, into the rodents’ mouths and stomachs. The animals’ food allergen sensitization disappeared, the team reports online today in the Proceedings of the National Academy of Sciences. When the scientists instead introduced another common kind of healthy bacteria, called Bacteroides, into similarly allergy-prone mice, they didn’t see the same effect. Studying the rodents more carefully, the researchers determined that Clostridia were having a surprising effect on the mouse gut: Acting through certain immune cells, the bacteria helped keep peanut proteins that can cause allergic reactions out of the bloodstream. “The bacteria are maintaining the integrity of the [intestinal] barrier,” Nagler says.
The research “opens up new territory,” Blaser says. It “extends the frontier of how the microbiome is involved” in immune responses and the roles played by specific bacteria. (Blaser’s group reported earlier this month in Cell that giving mice penicillin soon after birth changed their gut microbiome and made them much more likely to be obese as adults.) Nagler and her university have filed for a patent application on the new findings. The ultimate goal is to “interrupt [the allergy] process by manipulating the microbiota,” she says—a probiotic consisting of Clostridia could be a new allergy therapy, for example. Nagler knows of none on the market yet, and they would need testing in people before becoming a treatment of choice.
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.
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