The External Exposome and Allergies: From the Perspective of the Epithelial Barrier Hypothesis

Abstract

Introduction: In the last decades, we have seen a rapid increase in the prevalence of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergies. The environmental changes caused by industrialization, urbanization and modernization, including dramatic increases in air pollutants such as particulate matter (PM), diesel exhaust, nitrogen dioxide (NO2), ozone (O3), alarming effects of global warming, change and loss of biodiversity, affect both human health and the entire ecosystem.

Objective: In this review, we aimed to discuss the effects of the external exposome on epithelial barriers and its relationship with the development of allergic diseases by considering the changes in all stakeholders of the outer exposome together, in the light of the recently proposed epithelial barrier hypothesis.

Method: To reach current, prominent, and comprehensive studies on the subject, PubMed databases were searched. We included the more resounding articles with reliable and strong results.

Results: Exposure to altered environmental factors such as increased pollution, microplastics, nanoparticles, tobacco smoke, food emulsifiers, detergents, and household cleaners, and climate change, loss and change in microbial biodiversity, modifications in the consumption of dietary fatty acids, the use of emulsifiers, preservatives and the decrease in the antioxidant content of the widely consumed western diet may disrupt the epithelial barriers of the skin, respiratory and gastrointestinal tracts, making us more vulnerable to exogeneous allergens and microbes. Epithelial cell activation, microbial dysbiosis and bacterial translocation disrupt the immune balance and a chronic Th2 inflammation ensues.

Conclusion: Dramatic increases in air pollution, worrisome effects of global warming, dysbiosis, changing dietary habits and the complex interactions of all these factors affect the epithelial barriers and local and systemic inflammation. We want to draw attention to the emerging health effects of environmental changes and to motivate the public to influence government policies for the well-being of humans and the nature of the earth and the well-being of future generations.

Keywords: air pollution; climate change; epithelial barrier; exposome; microbiome; nutrition.

Figure 1

The effect of external exposome on epithelial barriers of skin lung and intestine. Due to climate change, extreme weather events have become more frequent and more intense. The air was polluted, and biodiversity was lost. Dietary preferences have shifted toward increased consumption of processed foods, n-6 fatty acids and GM foods. Exposure to environmental substances such as, detergents, PM, ozone, diesel exhaust, nanoparticles, microplastics, environmental tobacco smoke and airborne allergens were increased. Finally, the microbiome was affected, and increase in harmful commensals resulted in dysbiosis. All these factors affect and disrupt the epithelial barriers of skin, lung and gastrointestinal system and cause allergic diseases.

Figure 2

Interaction between environmental factors, epithelium, microbiota, and the immune system. Dysregulation of the epithelial barrier by genetic and environmental factors has been hypothesized to cause a leaky epithelium, which causes dysbiosis of microbial content, including commensals and opportunistic pathogens. Translocation of this content to interepithelial and subepithelial compartments and colonization of the opportunistic pathogens inducing peri-epithelial chronic inflammation. Finally chronic wound and continuous regeneration process ensues [adapted from reference (10)].