Fig. 1: General impact of microbial metabolite dysbiosis on allergic pathogenesis.

Microbial dysbiosis is a risk factor, occurring even before the onset of allergy pathogenesis. Microbial dysbiosis accompanies altered production of microbial metabolites, reducing the production of beneficial metabolites such as SCFAs, indole derivatives and BA metabolites, among others. At the same time, the production of harmful microbial metabolites or products from pathogenic microorganisms is increased. These changes weaken the barrier function in the skin, respiratory tract and intestine, increasing environmental or food antigen exposures to the immune system in the tissues. This process is called antigenic sensitization. Due to heightened expression of allergic alarmin cytokines such as TSLP, IL-25 and IL-33, the recruitment and tissue population of immune cells such as ILC2, eosinophils, basophils and mast cells are increased over time. DCs differentiated under these conditions would migrate to secondary lymphoid tissues, where they promote the differentiation of Th2, Tfh and Tc2 cells, which collectively induce allergen-specific IgE production by B cells and drive allergic tissue inflammation. Allergen-specific IgE molecules bind to the high-affinity receptor FcεRI on mast cells for their sensitization and ultimate activation by allergens and other inflammatory signals in tissues. Following repeated exposure to allergens, these processes are eventually amplified to pathogenic levels and cause chronic allergic diseases.