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.