Detergent-induced eosinophilic inflammation in the esophagus: A key evidence for the epithelial barrier theory.

Abstract

Since the 1960s, there has been an increasing prevalence of allergic, autoimmune, and metabolic diseases. Industrialization, urbanization, and a westernized lifestyle have brought several environmental factors to our lives such as detergents, surfactants, toothpastes, food emulsifiers and additives, cigarette smoke, particulate matter, diesel exhaust, ozone, nanoparticles and nano/microplastics, which can be toxic to our cells.1-3 Detergents used in laundry, dishwashing, and household cleaning agents are at the forefront substances that have gained cell toxicity properties with the addition of surfactants and enzymes after the 1960s, and substantial exposure to such substances including household cleaners, cosmetics, shampoos, toothpastes, etc. have been taking place in the public.1-3 There is clear evidence demonstrating an epidemiological link between the increased prevalence of allergic diseases, and exposure to detergents and cleaning products.4 Sodium dodecyl sulfate (SDS) and sodium dodecylbenzenesulfonate, two of the most frequently used detergent ingredients, disrupt the lung5 and skin6 epithelium's tight junction barrier, even at relatively low concentrations. In addition, a recent study showed that alcohol ethoxylates in rinse aid, a main ingredient of professional dishwasher detergents is toxic and inflammatory to gut epithelial cells.7 In this issue of Allergy, Doyle et al.8 reported the effects of SDS on esophageal barrier integrity, epithelial hyperplasia, and tissue eosinophilia. Immortalized esophageal epithelial cells were exposed to SDS and epithelial barrier integrity was assessed by transepithelial electrical resistance, paracellular flux, and real-time-PCR. The epithelial cell morphology was evaluated in ex vivo SDS-treated mouse organoid cultures. In addition, 0.5% SDS was administered to mice in their water to study histopathology, protein expression, and bulk RNA sequencing in vivo. Their findings demonstrate that epithelial cell death was induced by 25 μg/mL SDS after 2 h. In addition, epithelial barrier function was impaired, and the expression of IL-33 was increased, while desmoglein-1 expression was decreased by SDS. Ex vivo mouse esophageal organoid cultures demonstrated that SDS triggered basal epithelial disruption. Moreover, oral administration of SDS stimulates eosinophilic inflammation in the esophagus, together with abscess formation, basal zone hyperplasia, spongiosis, increased infiltration of eosinophils, neutrophils, and CD4+ T cells, and elevated levels of IL-33 and metalloproteinase expressions (Figure 1). RNA sequencing data demonstrated that exposure to SDS upregulates inflammatory and immune response-related pathways. The authors conclude that detergents and particularly SDS are the culprit agents that may affect the pathogenesis of eosinophilic esophagitis (EoE). The prevalence of EoE substantially increased after the demonstration of the first cases.9 This increase is in parallel to increased food allergy and anaphylaxis.10 Indeed, many substances with oral exposure still contain substantial levels of SDS. This includes laundry detergents, household cleaners, skin care products, and particularly toothpastes that can be relevant for EoE development.8 Oral exposure to substances such as toothpastes may show an impact on the integrity of oral epithelial cells.11 Important recent studies on molecular mechanisms of epithelial barrier damage7, 8 and preservation12, 13 have demonstrated that substances, such as SDS and alcohol ethoxylates may disrupt the epithelial barrier. Epithelial barrier theory explains that the onset of allergic, autoimmune, and metabolic diseases emerges as a result of exposure to a variety of substances that can damage the epithelial barriers. It describes the new concept of molecular toxicity and changes in the tissues at a molecular level. Opportunistic pathogen colonization, altered microbiota diversity, local inflammation, and incorrect regeneration and remodeling take place in tissues with a damaged epithelial barrier. Many chronic inflammatory diseases develop and worsen as a consequence of the migration of inflammatory cells to other tissues, which also contributes to tissue damage and inflammation in distant organs.14 Doyle et al.8 demonstrated that exposure to one of the most commonly used substances, SDS may have an effect on the epithelial cells in line with the epithelial barrier theory. To further protect the epithelial barriers and related microbiomes, it is currently very important to increase the research and public awareness in this area of molecular toxicity and alert regulatory authorities to revisit the commonly used doses of such substances. We would like to thank Dr Anna Globinska for assistance in generating the figure. CAA has received research grants from the Swiss National Science Foundation, Christine Kühne-Center for Allergy Research and Education, European Commission Horizon's 2020 Framework Programme “CURE”, Novartis Research Institutes, GlaxoSmithKline and AstraZeneca; served in the advisory board and received research grants from GlaxoSmithKline, Sanofi/Regeneron, SciBase, Seed-Health, and Novartis; appointed as Editor-in-Chief of Allergy. All other authors have no conflicts of interest to disclose. The author(s) reported there is no funding associated with the work featured in this article. The data that support the findings of this study are available from the corresponding author upon reasonable request.