The exposome in atopic dermatitis

Abstract

Atopic dermatitis (AD) is a complex inflammatory disorder with multiple interactions between genetic, immune and external factors. The sum of external factors that an individual is exposed to throughout their lifetime is termed the exposome. The exposome spans multiple domains from population to molecular levels and, in combination with genetic factors, holds the key to understanding the phenotypic diversity seen in AD patients. Exposomal domains are categorized into nonspecific (human and natural factors affecting populations), specific (eg humidity, ultraviolet radiation, diet, pollution, allergens, water hardness) and internal (cutaneous and gut microbiota and host cell interaction) exposures. The skin, as the organ that most directly interacts with and adapts to the external environment, is a prime target for exploration of exposomal influences on disease. Given the well-recognized physical environmental influences on AD, this condition could be much better understood through insightful exposomal research. In this narrative review, we examine each domain in turn, highlighting current understanding of the mechanisms by which exposomal influences modulate AD pathogenesis at distinct points in time. We highlight current approaches to exposome modification in AD and other allergic disease and propose future directions for exposome characterization and modification using novel research techniques.

Keywords: allergy; atopic dermatitis; exposome; microbiome.

Figure 1

The effect of nonspecific external exposures on AD pathogenesis. The interplay between nonspecific external exposures from both human and natural domains exerts an effect on AD pathogenesis. Patterns of economic development, migration and urbanization act as both cause and consequence of climate change and loss of biodiversity. Consequently, this increases susceptible individuals’ exposure to specific disease‐modifying exposures, alters the microbiome and interacts with host genetic and immune factors to contribute to AD flares. AD,atopic dermatitis

Figure 2

The role of airborne pollutants in AD pathogenesis. Airborne pollutants induce epigenetic modifications in utero, polarizing the immune response towards a TH2 phenotype, as well as directly damaging SC lipids and proteins. TH2 cytokines drive the characteristic inflammation and pruritus, as well as suppress FLG expression. The resulting itch‐scratch cycle further impairs the barrier through mechanical damage, driving inflammation and enabling direct contact with airborne pollutants, leading to a perpetuating cycle. AD, atopic dermatitis; APM, airborne particulate matter; NC, nitrogen compounds; RNS, reactive nitrogen species; ROS, reactive oxygen species; SC, stratum corneum; VOC, volatile organic compounds

Figure 3

The role of the cutaneous microbiome and its interaction with the exposome. Both lesional and nonlesional AD skin facilitates enhanced Staphylococcus aureus adherence and displays reduced microbial diversity. Staphylococcus aureus superantigen production facilitates TH2 cell influx, driving the characteristic inflammatory response. An exposomal approach aims to restore the normal cutaneous biodiversity via identifying positive and negative influences on the skin microbiome, thus enabling a degree of definitive prevention and amelioration in AD. The listed exposures do remain partly hypothetical at present, as further studies investigating the extent of their effect on cutaneous microbiome diversity are sought. AD, atopic dermatitis

Figure 4

Individual exposures, their doses and timing influence the interplay between the host microbiota, host immunity and genetics. The host gut and skin microbiota are entities sensitive to external manipulation by environmental influences, particularly at certain times in an individual's lifespan, such as the third trimester of gestation and the early neonatal period. Given the intimate interaction of the two microbiomes with each other via the gut‐skin axis and with the host's immune system, gut and skin dysbiosis are both likely to play a significant role in atopic dermatitis (AD) pathogenesis. The balance of detrimental and beneficial influences on the microbiome at critical time points determines the course of AD and allergy in the individual. The evidence regarding the above is varied in its robustness (strong evidence for breastfeeding, biodiversity, weak or emerging evidence for emollients, synbiotics and unpasteurized farm milk); however, it is the balance between a multitude of factors rather than individual factors in isolation that remain the pertinent factor in AD pathogenesis