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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:131

Article

Noval Rivas, Magali¹  Burton, Oliver T.²  Wise, Petra¹  Zhang, Yu-qian¹  Hobson, Suejy A.¹  Lloret, Maria Garcia¹  Chehoud, Christel³  Kuczynski, Justin³  DeSantis, Todd³  Warrington, Janet³  Hyde, Embriette R.^4,5  Petrosino, Joseph F.^4,6  Gerber, Georg K.⁷  Bry, Lynn⁷  Oettgen, Hans C.²  Mazmanian, Sarkis K.⁸  Chatila, Talal A.² 

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Immunol Allergy & Rheumatol, Los Angeles, CA 90095 USA

[2] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Immunol,Dept Pediat, Karp Family Bldg,1 Blackfan Circle, Boston, MA 02115 USA

[3] Second Genome Inc, San Bruno, CA USA

[4] Baylor Coll Med, Alkek Ctr Metagen & Microbiome Res, Houston, TX 77030 USA

[5] Baylor Coll Med, Interdept Program Cell & Mol Biol, Houston, TX 77030 USA

[6] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA

[7] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Clin & Translat Metagen,Dept Pathol, Boston, MA 02115 USA

[8] CALTECH, Div Biol, Pasadena, CA 91125 USA

关键词: Food allergy;    microbiome;    microbiota;    regulatory T cells;    tolerance;    anaphylaxis;    IgE;    16S rDNA;    IL-4 receptor;   

DOI  :  10.1016/j.jaci.2012.10.026

来源: Elsevier

【 摘 要 】

Background: Commensal microbiota play a critical role in maintaining oral tolerance. The effect of food allergy on the gut microbial ecology remains unknown. Objective: We sought to establish the composition of the gut microbiota in experimental food allergy and its role in disease pathogenesis. Methods: Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor alpha chain (Il4r alpha F709) 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. Results: OVA-sensitized Il4r alpha F709 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 Il4r alpha F709 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 Il4r alpha F709 mice differentially promoted OVA-specific IgE responses and anaphylaxis when reconstituted in WT germ-free mice. Conclusion: 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. (J Allergy Clin Immunol 2013;131:201-12.)

【 授权许可】

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