Noted FARE researcher Cathryn R. Nagler is the Bunning Food Allergy Professor and Professor of Pathology, Medicine and Pediatrics at The University of Chicago. At the 2017 FARE National Food Allergy Conference in San Antonio next week, she will be presenting a session on the trillions of bacteria in the human digestive tract, exploring how this gut microbiome may regulate immune responses to food proteins. Dr. Nagler has spoken previously at the FARE National Food Allergy Conference, and we are excited to hear about her latest research findings.
FARE: What first attracted you to food allergy research?
Dr. Nagler: I have been studying the mechanisms by which we maintain tolerance to dietary antigens since graduate school. My PhD thesis work was the first to show that tolerance to an autoantigen can be induced by oral administration of that antigen prior to induction of disease, using a mouse model of arthritis. This finding was replicated in many different animal models of autoimmune and allergic disease and was taken into multiple clinical trials. This is the concept behind antigen-specific oral immunotherapy. As the prevalence of food allergies began to increase I switched my focus to examining why tolerance to dietary antigens was failing in these patients.
FARE: What has sustained your interest?
Dr. Nagler: The dramatic generational increase in the prevalence of food allergies can’t be explained by a change in the antigen-specific response alone. It is increasingly clear that 21st century lifestyle factors, including overuse of antibiotics and anti-microbials, and highly processed low-fiber diets, have changed the composition of the trillions of bacteria that occupy all of the mucosal surfaces of our bodies but are most numerous in the gut. We identified a specific, allergy protective bacterial population that regulates allergen access into the bloodstream.
FARE: What experimental finding has surprised you the most, and why?
Dr. Nagler: In our first human studies, we found that as early as four months of age, the composition of the fecal microbiota in healthy infants is dramatically different from what we see in infants with cow’s milk allergy. When we transferred fecal material from the allergic infants to germ-free mice (which have no bacteria of their own) and sensitized these mice to cow’s milk, the mice died of anaphylaxis in response to oral challenge with a cow’s milk protein. Mice that received feces from healthy infants were protected. This study showed that we could transfer the infant’s clinical phenotype to a mouse with only transfer of feces – that was a big surprise.
FARE: How might your research affect patient care in the future?
Dr. Nagler: We have also identified a metabolite produced by these allergy protective bacteria that protects against allergic sensitization to food. We started a new company, ClostraBio, to develop this metabolite as a novel microbiome-modulating therapeutic to prevent or treat food allergies.
FARE: What unresolved question relating to food allergies would you most like to see answered?
Dr. Nagler: We want to move microbiome-modulating therapeutics into clinical trials and translate our mouse model work from the bench to the bedside.
FARE: You’ve spoken at the FARE National Food Allergy Conference before. What do you most look forward to at this year’s conference?
Dr. Nagler: I really enjoy talking about my work and answering audience questions. Although food allergy patients and parents are typically (of necessity) very well informed, they are usually engaged and enthusiastic to learn more, and to share their experiences.