A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis - 27/12/12
, Oliver T. Burton, PhD b, Petra Wise, PhD a, Yu-qian Zhang, PhD a, Suejy A. Hobson, MD a, Maria Garcia Lloret, MD a, Christel Chehoud, BA c, Justin Kuczynski, PhD c, Todd DeSantis, MSc c, Janet Warrington, PhD c, Embriette R. Hyde, BSc d, e, Joseph F. Petrosino, PhD d, f, Georg K. Gerber, MD, PhD g, Lynn Bry, MD, PhD g, Hans C. Oettgen, MD, PhD b, Sarkis K. Mazmanian, PhD h, Talal A. Chatila, MD, MSc a, ⁎ 
Corresponding author: Talal A. Chatila, MD, MSc, Division of Immunology, Boston Children’s Hospital, Karp Family Building, 1 Blackfan Circle, Boston, MA 02115.Abstract |
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 ⍺ 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.
Results |
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.
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.
El texto completo de este artículo está disponible en PDF.Key words : Food allergy, microbiome, microbiota, regulatory T cells, tolerance, anaphylaxis, IgE, 16S rDNA, IL-4 receptor
Abbreviations used : Foxp3, GF, HC-AN, IL-4R, iTreg, KW, mMCP-1, NMDS, OTU, OVA, PAM, rDNA, SEB, STAT6, TCR, Treg, WT
Esquema
| Supported by National Institutes of Health grants AI 080002 (to T.A.C.), AI007512 (to O.T.B.), DK034854 and DK078938 (to L.B.), HL07627 (to G.K.G.), AI100889 (to H.C.O.), and DK078938 (to S.K.M.); a grant from the Alkek Foundation (to J.F.P.); and the Department of Defense Congressionally Directed Medical Research Program in Food allergy grant FA100085 (to T.A.C.). |
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| Disclosure of potential conflict of interest: C. Chehoud, J. Kuczynski, T. DeSantis, and J. Warrington are employees of Second Genome. E. R. Hyde has received support from The Alkek Foundation. G. K. Gerber, L. Bry, and H. C. Oettgen have received research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 1
P. 201-212 - janvier 2013 Regresar al número
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