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

详细信息    查看全文

• 作者：Magali Noval Rivas ; PhD^a ; ^&lowast ; ; 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 ; ^&lowast ; ; ^{talal.chatila@childrens.harvard.edu}
• 关键词：Food allergy ; microbiome ; microbiota ; regulatory T cells ; tolerance ; anaphylaxis ; IgE ; 16S rDNA ; IL-4 receptor
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：131
• 期：1
• 页码：201-212
• 全文大小：2128 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

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 ¦Á 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.