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The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, humans have been increasingly exposed to substances toxic for epithelial cells, including air pollutants, laundry and dishwashers, household chemicals, toothpaste, food additives, microplastics, and nanoparticles, introduced into our daily lives as part of industrialization, urbanization, and modernization. These substances disrupt the epithelial barriers and lead to microbial dysbiosis and cause immune response to allergens, opportunistic pathogens, bacterial toxins, and autoantigens followed by chronic inflammation due to epigenetic mechanisms. Recent evidence from studies on the mechanisms of epithelial barrier damage has demonstrated that even trace amounts of toxic substances can damage epithelial barriers and induce tissue inflammation. Further research in this field is essential for our understanding of the causal substances and molecular mechanisms involved in the initiation of leaky epithelial barriers that cascade into chronic inflammatory diseases., Competing Interests: Declaration of Competing Interest Cezmi A. Akdis has received research grants from the Swiss National Science Foundation, European Union, Brussels, Belgium (EU CURE, EU Syn-Air-G), Novartis Research Institutes (Basel, Switzerland), Stanford University (Redwood City, California, USA), Seed Health (Boston, USA), AO Research Institute (Davos, Switzerland), and SciBase (Stockholm, Sweden). He is the Co-chair for the EAACI Guidelines on Environmental Science in Allergic Diseases and Asthma; Chair of the EAACI Epithelial Cell Biology Working Group; serves on the Advisory Boards of Sanofi/Regeneron (Bern, Switzerland, New York, USA), Stanford University Sean Parker Asthma Allergy Center (CA, USA), Novartis (Basel, Switzerland), GlaxoSmithKline (Zurich, Switzerland), Bristol-Myers Squibb (New York, USA), Seed Health (Boston, USA), and SciBase (Stockholm, Sweden). He is the Editor-in-Chief of Allergy. Mübeccel Akdis has received research grants from the Swiss National Science Foundation, Bern; a research grant from Stanford University and the Leading House for the Latin American Region, Seed Money Grant. She is on the Scientific Advisory Board of Stanford University-Sean Parker Asthma Allergy Center, CA; Advisory Board member of LEO Foundation Skin Immunology Research Center, Copenhagen, and Scientific Co-chair of the World Allergy Congress Istanbul, 2022, and Scientific Programme Committee Chair, EAACI, Zurich, Switzerland. I.O., Y.P., D.Y., S.A., O.A., and Y.M. declare no relevant conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)