- Bunning Food Allergy Professor
- Professor of Pathology, Medicine, Pediatrics and the College Committee on Immunology
B.A. Barnard College, Columbia University
Ph.D., New York University, Sackler Institute of Graduate Biomedical Science
The University of Chicago
924 East 57th Street
Chicago, Illinois 60637
Phone: (773) 702-6317
Regulation of allergic responses to food by the commensal microbiota
Life-threatening anaphylactic responses to food are a public health problem that shows no sign of abating. The Centers for Disease Control and Prevention has documented an 18% increase in the prevalence of reported food allergy among children in the U.S. during the ten-year period from 1997-2007. To understand what factors might be driving this increase, we have turned to the trillions of bacteria that populate our gastrointestinal tract, known collectively as the microbiome. Twenty-first century environmental interventions, including widespread antibiotic use, consumption of a high fat/low fiber Western diet, elimination of previously common enteropathogens (including helminthic parasites), reduced exposure to infectious disease, Caesarean birth and formula feeding have perturbed mutually beneficial interactions established with our commensal microbiome over millions of years of co-evolution. In genetically susceptible individuals, this dysbiosis can predispose to allergic disease.
Antibiotic use during infancy has often been cited as a factor in the rising prevalence of allergic disease. However, the mechanisms by which changes in the composition of the intestinal microbiota regulate allergic responses to food have been poorly understood. Murine models developed in our laboratory demonstrate that sensitization to a food allergen is enhanced in mice that have been treated by neonatal antibiotic administration (Abx) or are devoid of commensal microbes (germ free). By selectively colonizing germ free mice, we have shown that the allergy-protective capacity is contained within the Clostridia, a class of anaerobic spore-forming Firmicutes that reside in close proximity to the colonic epithelium. Moreover, reintroduction of a Clostridia-containing microbiota to Abx-treated mice blocks sensitization to a food allergen. Microarray analysis of intestinal epithelial cells isolated from gnotobiotic mice helped to identify a novel innate mechanism by which Clostridia protect against sensitization to dietary antigens. Defects in intestinal permeability have been implicated in aberrant allergic responses to food, but the mechanisms governing uptake of dietary antigen have not been clear. We find that Clostridia colonization induces the production of the barrier protective cytokine IL-22 by both innate lymphoid cells and T cells in the colonic lamina propria. IL-22 acts to reduce uptake of orally administered dietary antigen into the systemic circulation, thereby protecting against sensitization.
Ongoing work in our laboratory explores the cellular and molecular interactions by which commensal bacteria regulate sensitization to food allergens. Oral and subcutaneous allergen-specific desensitization protocols are already showing promise for treating food allergy. Our data suggest that pairing Clostridia enrichment of the gut microbiota with these tolerance inducing protocols may potentiate antigen specific tolerance to prevent or treat food allergy. We have launched a new company, ClostraBio,Inc. to develop microbiome-modulating therapeutics to prevent or treat food allergy.