The epithelial barrier: The gateway to allergic, autoimmune, and metabolic diseases and chronic neuropsychiatric conditions.

Since the 1960 s, our health has been compromised by exposure to over 350,000 newly introduced toxic substances, contributing to the current pandemic in allergic, autoimmune and metabolic diseases. The "Epithelial Barrier Theory" postulates that these diseases are exacerbated by persistent periepithelial inflammation (epithelitis) triggered by exposure to a wide range of epithelial barrier-damaging substances as well as genetic susceptibility. The epithelial barrier serves as the body's primary physical, chemical, and immunological barrier against external stimuli. A leaky epithelial barrier facilitates the translocation of the microbiome from the surface of the afflicted tissues to interepithelial and even deeper subepithelial locations. In turn, opportunistic bacterial colonization, microbiota dysbiosis, local inflammation and impaired tissue regeneration and remodelling follow. Migration of inflammatory cells to susceptible tissues contributes to damage and inflammation, initiating and aggravating many chronic inflammatory diseases. The objective of this review is to highlight and evaluate recent studies on epithelial physiology and its role in the pathogenesis of chronic diseases in light of the epithelial barrier theory.
Competing Interests: Declaration of Competing Interest CA 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. YM and WV report grants from Novartis. MS reports grants from the Swiss National Science Foundation, GSK and Novartis. KN reports grants from National Institute of Allergy and Infectious Diseases (United States), National Heart, Lung, and Blood Institute (United States), National Institute of Environmental Health Sciences (United States), and Food Allergy Research & Education (United States); stock options from IgGenix, Seed Health, ClostraBio, and ImmuneID (United States). All other authors have no conflicts of interest to disclose.
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