title: Germ-free status and altered caecal subdominant microbiota are associated with a high susceptibility to cow's milk allergy in mice.
abstract: Studies suggesting that the development of atopy is linked to gut microbiota composition are inconclusive on whether dysbiosis precedes or arises from allergic symptoms. Using a mouse model of cow's milk allergy, we aimed at investigating the link between the intestinal microbiota, allergic sensitization, and the severity of symptoms. Germ-free and conventional mice were orally sensitized with whey proteins and cholera toxin, and then orally challenged with β-lactoglobulin (BLG). Allergic responses were monitored with clinical symptoms, plasma markers of sensitization, and the T-helper Th1/Th2/regulatory-T-cell balance. Microbiota compositions were analysed using denaturing gradient gel electrophoresis and culture methods. Germ-free mice were found to be more responsive than conventional mice to sensitization, displaying a greater reduction of rectal temperature upon challenge, higher levels of blood mouse mast cell protease-1 (mMCP-1) and BLG-specific immunoglobulin G1 (IgG1), and a systemic Th2-skewed response. This may be explained by a high susceptibility to release mMCP-1 even in the presence of low levels of IgE. Sensitization did not alter the microbiota composition. However, the absence of or low Staphylococcus colonization in the caecum was associated with high allergic manifestations. This work demonstrates that intestinal colonization protects against oral sensitization and allergic response. This is the first study to show a relationship between alterations within the subdominant microbiota and severity of food allergy.
authors.affiliation: EA 4065, Ecosystème intestinal, Probiotiques, Antibiotiques, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Guénolée
authors.initials: G
authors.lastname: Prioult
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bibiloni
authors.forename: Ioannis
authors.initials: I
authors.lastname: Nicolis
authors.forename: Annick
authors.initials: A
authors.lastname: Mercenier
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Butel
authors.forename: Anne-Judith
authors.initials: AJ
authors.lastname: Waligora-Dupriet
mesh_terms: D000818:Animals; D002417:Cattle; D002432:Cecum / Q000276:immunology / Q000382:microbiology*; D053818:Chymases / Q000097:blood / Q000276:immunology; D004269:DNA, Bacterial / Q000302:isolation & purification; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005856:Germ-Free Life; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007782:Lactoglobulins / Q000494:pharmacology; D054892:Metagenome / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D016269:Milk Hypersensitivity / Q000097:blood / Q000276:immunology*; D008894:Milk Proteins / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000067816:Whey Proteins
chemical_list: D004269:DNA, Bacterial; D007074:Immunoglobulin G; D007782:Lactoglobulins; D008894:Milk Proteins; D000067816:Whey Proteins; D007073:Immunoglobulin E; D053818:Chymases; C509230:Mcpt1 protein, mouse