The skin microbiome in food allergy pathogenesis
Food allergy (FA) is closely associated with AD, particularly in the early-onset severe phenotype. Murine studies have demonstrated that the pathogenesis of food allergy may occur through epicutaneous sensitization to food allergens through the disrupted skin barrier in AD (Figure 2). In these murine studies, these mechanistic pathways are postulated to involve activation of dermal antigen-presenting cells upon exposure of inflamed skin to exogenous food allergens, germinal centre IgE+ B cell expansion and generation of food allergen-specific IgE and other pro-inflammatory cytokines (IL-4, IL-5, thymic stromal lymphopoietin (TSLP) and IL-33).64, 65
Recent studies have increasingly highlighted the association of skin microbes with the AD-FA axis. Jones et al found that children (n=718; aged 0–18 years) with AD who were colonized with S. aureus , particularly MRSA, also had a higher risk of food allergy compared to healthy controls.66Infants from the Learning About Peanut Allergy (LEAP) study who wereS. aureus- colonized during at least one time-point between 4 and 60 months of age had increased risk of peanut and egg allergy in the first 5 years of life, independent of AD severity.67 A murine model demonstrated that combined epicutaneous exposure to staphylococcal enterotoxin B (SEB) and OVA enhanced OVA-specific IgE and IgG2 antibody responses compared to OVA exposure alone.68 Mice which were cutaneously sensitized with SEB and peanut allergen extract had significantly increased peanut-specific Th2 responses compared to mice sensitized with peanut allergen alone.69 These mouse experiments suggest that SEB may perform an adjunctive role in mediating food allergy through AD skin.
A cross-sectional metagenomic study (n=62; children aged 4–17 years) of skin microbiota collected from AD patients with food allergy (ADFA+) showed an increased S. aureus relative abundance on their non-lesional skin as compared to healthy subjects. S. aureusabundance also positively correlated with transepidermal water loss in the ADFA+ group but not in AD patients without food allergy (ADFA-) or healthy groups.70 There is, however, a paucity of studies on the differences in overall skin microbiota composition (apart from S. aureus alone), and the temporal evolution of the skin microbiome alongside immune dysregulation, in the development of AD and food allergy.