Antibiotic induced alterations in the commensal microbiome reduce CD4+Foxp3+ Tregs in the colonic lamina propria and increase allergic responses to food (175.14)

Abstract

Abstract Antibiotic (Abx) use in early life has been implicated in the increasing prevalence of food allergy, presumably due to its effects on the commensal bacterial microbiome. To gain insight into the mechanisms by which commensal bacteria regulate allergic responses to food, C57Bl/6 mice were treated with a cocktail of Abx, beginning by gavage at two weeks of age and continuing in the drinking water after weaning. 16S rDNA based pyrosequence analysis demonstrated that Abx treatment significantly altered the composition and diversity of the fecal microbiota; Lachnospiraceae (Clostridia) were significantly reduced and Bacteroidaceae were enriched in fecal samples obtained from Abx treated mice. Reduced Clostridia abundance correlated with significantly decreased proportions of CD4+Foxp3+ Tregs in the colonic lamina propria, but not the spleen or mesenteric lymph node, of Abx treated mice compared to untreated controls. Elevated allergen specific IgE and IgG1 responses were induced in Abx treated (but not untreated) mice sensitized with purified peanut extract plus cholera toxin. Transfer of CD4+Foxp3+Tregs from untreated mice, prior to sensitization, blocked the allergen specific IgE response induced by Abx treatment. Our data supports the hypothesis that bacteria (Clostridia) induce CD4+Foxp3+ Tregs in the colonic mucosa. These Tregs are depleted (and protection against an allergic response to food is reduced) in Abx treated mice.