title: The role of commensal bacteria in the regulation of sensitization to food allergens.
abstract: The prevalence of life-threatening anaphylactic responses to food is rising at an alarming rate. The emerging role of the gut microbiota in regulating food allergen sensitization may help explain this trend. The mechanisms by which commensal bacteria influence sensitization to dietary antigens are only beginning to be explored. We have found that a population of mucosa-associated commensal anaerobes prevents food allergen sensitization by promoting an IL-22-dependent barrier protective immune response that limits the access of food allergens to the systemic circulation. This early response is followed by an adaptive immune response mediated in part by an expansion of Foxp3(+) Tregs that fortifies the tolerogenic milieu needed to maintain non-responsiveness to food. Bacterial metabolites, such as short-chain fatty acids, may contribute to the process through their ability to promote Foxp3(+) Treg differentiation. This work suggests that environmentally induced alterations of the gut microbiota offset the regulatory signals conferred by protective bacterial species to promote aberrant responses to food. Our research presents exciting new possibilities for preventing and treating food allergies based on interventions that modulate the composition of the gut microbiota.
authors.affiliation: Department of Pathology and Committee on Immunology, The University of Chicago, 924 East 57th Street, JFK R120, Chicago, IL 60637, United States.
authors.forename: Severine
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Pathology and Committee on Immunology, The University of Chicago, 924 East 57th Street, JFK R120, Chicago, IL 60637, United States.
authors.forename: Taylor J
authors.initials: TJ
authors.lastname: Feehley
authors.affiliation: Department of Pathology and Committee on Immunology, The University of Chicago, 924 East 57th Street, JFK R120, Chicago, IL 60637, United States. Electronic address: cnagler@bsd.uchicago.edu.
authors.forename: Cathryn R
authors.initials: CR
authors.lastname: Nagler
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D018407:Bacterial Physiological Phenomena; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005512:Food Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis; D013559:Symbiosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D000485:Allergens; D005227:Fatty Acids; D007378:Interleukins; D000097043:Interleukin-22
keywords: Food allergy; Foxp3(+) Tregs; IL-22; Intestinal microbiota; Oral tolerance; Short chain fatty acids