Commensal Bacteria and Their Metabolites Reduce Intestinal Permeability to Protect Against Food Allergen Sensitization

Food allergies are a growing public health concern. We have identified a consortium of spore-forming Firmicutes from the Clostridia class that prevents food allergen sensitization when administered to neonatal antibiotic-treated or germ free (GF) mice. Protection was characterized by reduced serum concentrations of the peanut allergens Ara h 2 and 6 in orally challenged Clostridia-colonized mice and required the induction of IL-22 in the intestinal lamina propria (LP). We examined whether Clostridia mediate their epithelial barrier protective effects through direct interaction with the host or through the secretion of metabolites. Heat-inactivation abrogated Clostridia-induced expression of IL-22, but not IL-12, in the intestinal LP. Heat-inactivated Clostridia also failed to reduce serum concentrations of either FITC-labeled dextran or Ara h 2/6, suggesting a possible protective role for bacterial metabolites. Short chain fatty acids (SCFA) are important immunoregulatory metabolites of this bacterial class. Metabolomic analysis revealed that our Clostridia consortium produces both butyrate and acetate. We found that administration of butyrate, but not acetate, to GF mice induces IL-22 expression and reduces serum Ara h 2/6 concentrations. Our data suggest that the production of the SCFA butyrate is one mechanism by which Clostridia induce a barrier protective response that prevents sensitization to food.