Legends:
Figure 1. Prevalence of Paediatric
FA Around the World adapted from Warren C, Jiang J, Gupta
R.Epidemiology and Burden of Food Allergy. Curr Allergy Asthma
Rep. 2020;20(2), Lyons SA,
Clausen M, Knulst AC, et al. Prevalence of Food Sensitization and Food
Allergy in Children
Across Europe. J Allergy Clin Immunol Pract. 2020;8(8):2736-2746
e2739 and Venter C, Pereira B, Voigt K, et al. Prevalence and cumulative
incidence of food hypersensitivity
in the first 3 years of life. Allergy. 2008;63(3):354-359.
Figure 2: Prevalence of Current
Eczema Symptoms (ISAAC Phase III: Ages 6-7 adapted from Odhiambo J,
Williams H, Clayton T, Robertson C, Asher M. Global variations in
prevalence of eczema symptoms in children from ISAAC Phase Three.J Allergy Clin Immunol. 2009;124(6):1251-1258
Figure 3: Prevalence of Current
Eczema Symptoms (ISAAC Phase III: Ages 13-14) adapted from from Odhiambo
J, Williams H, Clayton T, Robertson C, Asher M. Global variations in
prevalence of eczema symptoms in children from ISAAC Phase Three.J Allergy Clin Immunol. 2009;124(6):1251-1258
Figure 4: In the “outside-in” hypothesis, skin barrier defect allows
penetration of allergens and
microbes leading to atopic sensitization whereas, in the “inside-out”
paradigm, a polarized
immune response leads to a defective skin barrier. Adapted from Leung
DY, Guttman-Yassky E.
Deciphering the complexities of atopic dermatitis: Shifting paradigms in
treatment approaches.
J Allergy Clin Immunol. 2014;134(4):769-779.
Figure 5: Skin dysbiosis, especially colonization ofStaphylococcus aureus and Malassezia spp., is often seen
among young children with atopic dermatitis. (a) S. aureuscolonization on a six-month child; (b). heavy colonization ofMalassezia spp., also known as Pityrosporum, on the scalp of an
infant.
Figure 6: Dietary compounds and their conversion by commensal bacteria
influence oral tolerance. Several dietary components and digestive
products contribute heavily to the function of the gut immune system.
Gut-resident CD103+ dendritic cells (DCs) directly
convert dietary vitamin A to retinoic acid (RA) for further downstream
immune signaling. Conversely, tryptophan, liver-derived bile acids, and
fiber must first be metabolized by commensal bacteria such as
Clostridia. These bacteria degrade tryptophan into several compounds
that can bind to the aryl-hydrocarbon receptor (Ahr) of ILC3s, playing a
role in IL-22 production. Secondary bile acids and short chain fatty
acids (SCFAs), including butyrate, signal directly to epithelial cells
as well as local immune cell populations residing in the lamina propria.
Collectively, these compounds enhance epithelial barrier integrity by
stimulating Paneth cells to produce anti-microbial peptides, goblet
cells to produce mucus, and epithelial cells to produce tight junction
and adherens proteins. In addition, they induce populations of
tolerogenic lymphocytes such as peripherally induced regulatory T cells
(iTregs) and IgA-producing plasma cells. Together, these functions are
essential for the maintenance of oral tolerance.
Figure 7: Diagram of possible causal associations between genetics, skin
exposures, diet leading to eczema and/or food allergy. The interplay
between genetics, diet, and skin/microbiome exposure are connected by
arrows showing the direction of causality hypothesized to ultimately
influence food allergy. The relevant causal factors of the dual allergen
exposure hypothesis are outlined by the blue rectangle. This hypothesis
postulates that allergen exposure through the skin leads to the
development of food allergy. The degree of a broken skin barrier
involved with eczema is thought to interact with allergen exposure to
increase the probability of allergy development with increasing barrier
disfunction. While early introduction of food and diet diversity has
been proven to prevent food allergy (dark green), other factors such as
breastfeeding, commensal bacteria metabolizing bile acids, tryptophan
from dietary/commensal bacterial sources, dietary fiber, vitamins,
pre-pro- and syn-biotics have weaker evidence base for this (light
green). Reducing eczema severity has yet to be consistently shown as a
preventative causal mechanism. Nevertheless, eczema severity exists as
one of the strongest predictors of food allergy, and therapies to heal a
broken skin barrier remain as a leading mechanism to mediate the
prevention of food allergy.