Regulation of oral immune tolerance by the microbiome in food allergy

• Published in: Current opinion in immunology Vol. 60; pp. 141 - 147
• Main Authors: Stephen-Victor, Emmanuel, Chatila, Talal A
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2019
• Subjects: Animals; Disease Susceptibility - immunology; Dysbiosis - immunology; Food Hypersensitivity - genetics; Food Hypersensitivity - immunology; Food Hypersensitivity - therapy; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Immune Tolerance; Immunomodulation; Microbiota - immunology; Precision Medicine; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism
• ISSN: 0952-7915; 1879-0372; 1879-0372
• DOI: 10.1016/j.coi.2019.06.001

•Food allergy (FA) is characterized by pathogenic dysbiosis.•The dysbiosis in FA disrupts oral tolerance to dietary antigens by impairing the generation of ROR-γt+ induced regulatory T cells.•Therapy with Clostridiales and Bacteroidales commensal bacteria activates a MyD88- ROR-γt axis in nascent iTreg cells to restore immune tolerance in FA. The steep rise in the incidence and prevalence of food allergy (FA) in the last few decades have focused attention of environmental mechanisms which act to promote disease, chief among which is the microbiome. Recent studies have now established the presence of pathogenic dysbiosis in FA that could be precipitated by a variety of environmental insults, including among others antibiotic usage and mode of delivery, that act to subvert the immune regulatory response that enforce tolerance to dietary antigens. A key attribute of this dysbiosis is the loss of Clostridial bacterial species that act to promote the formation of food allergen-specific nascent regulatory T cells in the gut. Significantly, different immunoprotective commensal bacteria, including members of the Clostridiales and Bacteroidales orders act to induce the transcription factor RORγt in nascent Treg cells via an upstream MyD88-dependent mechanism to promote tolerance to dietary antigens. Activation of this axis is disrupted by the dysbiosis, and can be restored by treatment with therapeutic microbiota. These findings highlight the potential for novel microbiota-based approaches to the prevention and treatment of the FA epidemic.