Bacterial metabolites reduce intestinal permeability to protect against food allergen sensitization (MUC8P.724)

Abstract Food allergies are a growing public health concern. Our laboratory has recently identified a consortium of Firmicutes from the Clostridia class that can protect germ free (GF) or antibiotic (Abx)-treated mice against sensitization to peanut. This Clostridia consortium induces an early innate cytokine response in the colonic lamina propria that is characterized by the production of the barrier protective cytokine IL-22. By measuring the concentrations of two immunodominant peanut allergens, Ara h 2 and Ara h 6, in serum post gavage we demonstrated that Clostridia-induced IL-22 is necessary and sufficient to reduce intestinal permeability in neonatal Abx-treated mice. Administration of FITC-labeled dextran molecules of different sizes has further interrogated the effect of Clostridia colonization on intestinal permeability to food allergens. Treatment of GF mice with heat-killed Clostridia did not induce IL-22 or reduce intestinal permeability, suggesting a role for bacterial metabolites in mediating protection. Metabolomic analysis revealed that our Clostridia consortium produces high levels of the short chain fatty acids acetate and butyrate. Administration of acetate or butyrate to GF mice showed that only butyrate induced IL-22 and reduced the concentration of peanut allergen in the blood after challenge. We propose that production of butyrate is one mechanism by which Clostridia can influence intestinal permeability and host susceptibility to allergic sensitization.