title: A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis.
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 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Magali
authors.initials: M
authors.lastname: Noval Rivas
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Burton
authors.forename: Petra
authors.initials: P
authors.lastname: Wise
authors.forename: Yu-qian
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Suejy A
authors.initials: SA
authors.lastname: Hobson
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia Lloret
authors.forename: Christel
authors.initials: C
authors.lastname: Chehoud
authors.forename: Justin
authors.initials: J
authors.lastname: Kuczynski
authors.forename: Todd
authors.initials: T
authors.lastname: DeSantis
authors.forename: Janet
authors.initials: J
authors.lastname: Warrington
authors.forename: Embriette R
authors.initials: ER
authors.lastname: Hyde
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.forename: Georg K
authors.initials: GK
authors.lastname: Gerber
authors.forename: Lynn
authors.initials: L
authors.lastname: Bry
authors.forename: Hans C
authors.initials: HC
authors.lastname: Oettgen
authors.forename: Sarkis K
authors.initials: SK
authors.lastname: Mazmanian
authors.forename: Talal A
authors.initials: TA
authors.lastname: Chatila
mesh_terms: D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology / Q000382:microbiology; D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005502:Food / Q000009:adverse effects; D005512:Food Hypersensitivity / Q000276:immunology* / Q000382:microbiology* / Q000628:therapy; D005516:Food Microbiology; D007108:Immune Tolerance / Q000276:immunology; D016219:Immunotherapy, Adoptive; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D008297:Male; D054892:Metagenome / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010802:Phylogeny; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
chemical_list: D000485:Allergens