Commensal bacteria signal through TLR5 and AhR to improve barrier integrity and prevent allergic responses to food

Summary: The increasing prevalence of food allergies has been linked to reduced commensal microbial diversity. In this article, we describe two features of allergy-protective Clostridia that contribute to their beneficial effects. Some Clostridial taxa bear flagella (a ligand for TLR5) and produce indole (a ligand for the aryl hydrocarbon receptor [AhR]). Lysates and flagella from a Clostridia consortium induced interleukin-22 (IL-22) secretion from ileal explants. IL-22 production is abrogated in explants from mice in which TLR5 or MyD88 signaling is deficient either globally or conditionally in CD11c+ antigen-presenting cells. AhR signaling in RORγt+ cells is necessary for the induction of IL-22. Mice deficient in AhR in RORγt+ cells exhibit increased intestinal permeability and are more susceptible to an anaphylactic response to food. Our findings implicate TLR5 and AhR signaling in a molecular mechanism by which commensal Clostridia protect against allergic responses to food

Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles

The microbiome modulates host immunity and aids the maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Yet modern dietary factors and the excessive use of antibiotics have contributed to the rising incidence of food allergies, inflammatory bowel disease and other non-communicable chronic diseases associated with the depletion of beneficial taxa, including butyrate-producing Clostridia. Here we show that intragastrically delivered neutral and negatively charged polymeric micelles releasing butyrate in different regions of the intestinal tract restore barrier-protective responses in mouse models of colitis and of peanut allergy. Treatment with the butyrate-releasing micelles increased the abundance of butyrate-producing taxa in Clostridium cluster XIVa, protected mice from an anaphylactic reaction to a peanut challenge and reduced disease severity in a T-cell-transfer model of colitis. By restoring microbial and mucosal homoeostasis, butyrate-releasing micelles may function as an antigen-agnostic approach for the treatment of allergic and inflammatory diseases