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.