Epithelial barrier hypothesis and the development of allergic and autoimmune diseases

The “epithelial barrier hypothesis” proposes that genetic predisposition to epithelial barrier damage, exposure to various epithelial barrier–damaging agents and chronic periepithelial inflammation are responsible for the development of allergic and autoimmune diseases. Particularly, the introduction of more than 200,000 new chemicals to our daily lives since the 1960s has played a major role in the pandemic increase of these diseases. The epithelial barrier constitutes the first line of physical, chemical, and immunological defence against external factors. A leaky epithelial barrier initiates the translocation of the microbiome from the surface of affected tissues to interepithelial and even deeper subepithelial areas. In tissues with a defective epithelial barrier, colonization of opportunistic pathogens, decreased microbiota biodiversity, local inflammation, and impaired regeneration and remodelling takes place. A dysregulated immune response against commensals and opportunistic pathogens starts. Migration of inflammatory cells to other tissues and their contribution to tissue injury and inflammation in the affected tissues are key events in the development and exacerbation of many chronic inflammatory diseases. Understanding the underlying factors that affect the integrity of epithelial barriers is essential to find preventive measures or effective treatments to restore its function. The aim of this review is to assess the origins of allergic and autoimmune diseases within the framework of the epithelial barrier hypothesis

Disrupted epithelial permeability as a predictor of severe COVID-19 development

BackgroundAn impaired epithelial barrier integrity in the gastrointestinal tract is important to the pathogenesis of many inflammatory diseases. Accordingly, we assessed the potential of biomarkers of epithelial barrier dysfunction as predictive of severe COVID‐19.MethodsLevels of bacterial DNA and zonulin family peptides (ZFP) as markers of bacterial translocation and intestinal permeability and a total of 180 immune and inflammatory proteins were analyzed from the sera of 328 COVID‐19 patients and 49 healthy controls.ResultsSignificantly high levels of circulating bacterial DNA were detected in severe COVID‐19 cases. In mild COVID‐19 cases, serum bacterial DNA levels were significantly lower than in healthy controls suggesting epithelial barrier tightness as a predictor of a mild disease course. COVID‐19 patients were characterized by significantly elevated levels of circulating ZFP. We identified 36 proteins as potential early biomarkers of COVID‐19, and six of them (AREG, AXIN1, CLEC4C, CXCL10, CXCL11, and TRANCE) correlated strongly with bacterial translocation and can be used to predict and discriminate severe cases from healthy controls and mild cases (area under the curve (AUC): 1 and 0.88, respectively). Proteomic analysis of the serum of 21 patients with moderate disease at admission which progressed to severe disease revealed 10 proteins associated with disease progression and mortality (AUC: 0.88), including CLEC7A, EIF4EBP1, TRANCE, CXCL10, HGF, KRT19, LAMP3, CKAP4, CXADR, and ITGB6.ConclusionOur results demonstrate that biomarkers of intact or defective epithelial barriers are associated with disease severity and can provide early information on the prediction at the time of hospital admission

Effect of altered human exposome on the skin and mucosal epithelial barrier integrity

Pollution in the world and exposure of humans and nature to toxic substances is continuously worsening at a rapid pace. In the last 60 years, human and domestic animal health has been challenged by continuous exposure to toxic substances and pollutants because of uncontrolled growth, modernization, and industrialization. More than 350,000 new chemicals have been introduced to our lives, mostly without any reasonable control of their health effects and toxicity. A plethora of studies show exposure to these harmful substances during this period with their implications on the skin and mucosal epithelial barrier and increasing prevalence of allergic and autoimmune diseases in the context of the "epithelial barrier hypothesis". Exposure to these substances causes an epithelial injury with peri-epithelial inflammation, microbial dysbiosis and bacterial translocation to sub-epithelial areas, and immune response to dysbiotic bacteria. Here, we provide scientific evidence on the altered human exposome and its impact on epithelial barriers. Keywords: Detergents; epithelial barrier; exposome; microplastics; nanoparticles; ozone; particulate matter