Figure 2.

Role of the microbiota in epithelial regulation of food allergy. Diet and the intestinal microbiota interact to produce the outgrowth or loss of certain bacterial genera in food allergy this can result in altered concentration of microbial ligands, such as TLR ligands, and small molecule metabolites that stimulate host epithelial and immune responses. CpG oligonucleotides from bacterial DNA bind epithelial TLR9 to increase expression of ZO-1 improving epithelial tight junction barrier integrity to antigen and reducing cytokine production from immune cells. A high-fiber diet leads to outgrowth of many fermenting Clostridial species and enable their production of short chain fatty acids (SCFAs), in particular butyrate, that act on the epithelium to induce goblet cell hyperplasia, increase antimicrobial proteins (Reg3β and γ), and reduce TLR4 expression. SCFAs also inhibit mast cell activation and favor the development of tolerogenic dendritic cells (DCs) and regulatory T cells and suppress the inflammatory DC-Th2-IgE pathway. A high-fat diet leads to increase in Bacteroidetes and Deltaproteobacteria and reduction in abundance of Prevoltellaceae. This microbial dysbiosis drives increased barrier permeability and antigen transfer to lamina propria cells by increasing Claudin2 and decreasing Occludin tight junction expression. The soluble microbial factors responsible for this epithelial change remain to be discovered.