Gut bacteria that protect against food allergies identifiedAugust 25, 2014
This story was first reported by the University of Chicago Medicine and Biological Sciences.
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.
"From a basic science perspective, what is fascinating with this research is the fine-scale machinations that the host microbiome exhibits with its host," said Dionysios Antonopoulos of the Institute for Genomics and Systems Biology at Argonne National Laboratory and a co-author for the study. "Specific populations of microorganisms serve specific functions in mediating how the host's immune system senses and interacts with its environment. As with this study, understanding how specific populations of the microbial community are impacted by antibiotics or diet provides a guide on what therapeutic strategies need to be developed to restore a healthy state."
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."
The study, "Commensal bacteria protect against food allergen sensitization," was supported by Food Allergy Research & Education (FARE) and the University of Chicago Digestive Diseases Research Core Center. Gene sequencing was conducted at the Next-Generation Sequencing Core at Argonne National Laboratory. Additional authors include Andrew T. Stefka, Taylor Feehley, Prabhanshu Tripathi, Ju Qiu, Kathy D. McCoy, Sarkis K. Mazmanian, Melissa Y. Tjota, Goo-Young Seo, Severine Cao, Betty R. Theriault, Dionysios A. Antonopoulos, Liang Zhou, Eugene B. Chang and Yang-Xin Fu.
Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science. DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.
Food Allergy Research & Education (FARE) is a 501(c)(3) nonprofit organization that seeks to find a cure for food allergies while keeping affected individuals safe and included. FARE does this by investing in world-class research that advances the treatment and understanding of the disease, providing evidence-based education and resources, undertaking advocacy at all levels of government and increasing awareness of food allergy as a serious public health issue.
The University of Chicago Medicine and Biological Sciences is one of the nation's leading academic medical institutions. It comprises the Pritzker School of Medicine, a top medical school in the nation; the University of Chicago Biological Sciences Division; and the University of Chicago Medical Center, which recently opened the Center for Care and Discovery, a $700 million specialty medical facility. Twelve Nobel Prize winners in physiology or medicine have been affiliated with the University of Chicago Medicine.