A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 1; pp. 201 - 212
• Main Authors: Noval Rivas, Magali, Burton, Oliver T., Wise, Petra, Zhang, Yu-qian, Hobson, Suejy A., Garcia Lloret, Maria, Chehoud, Christel, Kuczynski, Justin, DeSantis, Todd, Warrington, Janet, Hyde, Embriette R., Petrosino, Joseph F., Gerber, Georg K., Bry, Lynn, Oettgen, Hans C., Mazmanian, Sarkis K., Chatila, Talal A.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.01.2013; Elsevier; Elsevier Limited
• Subjects: 16S rDNA; Administration, Oral; Allergens - administration & dosage; Allergens - immunology; Allergic diseases; Allergies; Allergy and Immunology; anaphylaxis; Anaphylaxis - immunology; Anaphylaxis - microbiology; Animals; Biological and medical sciences; Body temperature; chickens; community structure; Digestive allergic diseases; Disease; disease resistance; Disease Susceptibility - immunology; eggs; Female; Food; Food - adverse effects; Food allergies; Food allergy; Food Hypersensitivity - immunology; Food Hypersensitivity - microbiology; Food Hypersensitivity - therapy; Food Microbiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; germ-free animals; IgE; IL-4 receptor; Immune Tolerance - immunology; immunoglobulin E; Immunopathology; Immunotherapy, Adoptive; Industrialized nations; interleukin-4; intestinal microorganisms; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Lactobacillaceae; Lymphocytes; Male; Medical sciences; Metagenome - genetics; Metagenome - immunology; Mice; Mice, Transgenic; microarray technology; microbial ecology; microbiome; microbiota; mutation; oligonucleotides; ovalbumin; Pathogenesis; Phylogeny; regulatory T cells; Ribosomal DNA; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; sequence analysis; Studies; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; tolerance; microbiota; Food allergy; TCR; regulatory T cells; IgE; iTreg; IL-4 receptor; anaphylaxis; mMCP-1; OTU; 16S rDNA; STAT6; WT; tolerance; GF; Treg; HC-AN; NMDS; KW; microbiome; IL-4R; rDNA; SEB; OVA; Foxp3; PAM; Murine mast cell protease 1; Kruskal-Wallis; Ribosomal DNA; T-cell receptor; Hierarchical clustering-average-neighbor; Signal transducer and activator of transcription 6; Forkhead box protein 3; Regulatory T; Induced regulatory T; Ovalbumin; Wild-type; Nonmetric multidimensional scaling; Germ free; Staphylococcal enterotoxin B; Operational taxonomic unit; Prediction Analysis for Microarrays; Immunopathology; Cytokine; Tolerance; Experimental study; regulatory T cells; Interleukin 4; Anaphylaxis; Association; Immunology; T-Lymphocyte; Digestive diseases; Sensitization; Regulatory cell; Biological receptor
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.10.026

Commensal microbiota play a critical role in maintaining oral tolerance. The effect of food allergy on the gut microbial ecology remains unknown. We sought to establish the composition of the gut microbiota in experimental food allergy and its role in disease pathogenesis. Food allergy–prone mice with a gain-of-function mutation in the IL-4 receptor α chain (Il4raF709) and wild-type (WT) control animals were subjected to oral sensitization with chicken egg ovalbumin (OVA). Enforced tolerance was achieved by using allergen-specific regulatory T (Treg) cells. Community structure analysis of gut microbiota was performed by using a high-density 16S rDNA oligonucleotide microarrays (PhyloChip) and massively parallel pyrosequencing of 16S rDNA amplicons. OVA-sensitized Il4raF709 mice exhibited a specific microbiota signature characterized by coordinate changes in the abundance of taxa of several bacterial families, including the Lachnospiraceae, Lactobacillaceae, Rikenellaceae, and Porphyromonadaceae. This signature was not shared by similarly sensitized WT mice, which did not exhibit an OVA-induced allergic response. Treatment of OVA-sensitized Il4raF709 mice with OVA-specific Treg cells led to a distinct tolerance-associated signature coincident with the suppression of the allergic response. The microbiota of allergen-sensitized Il4raF709 mice differentially promoted OVA-specific IgE responses and anaphylaxis when reconstituted in WT germ-free mice. Mice with food allergy exhibit a specific gut microbiota signature capable of transmitting disease susceptibility and subject to reprogramming by enforced tolerance. Disease-associated microbiota may thus play a pathogenic role in food allergy.