Open Access

Na Sun, Ismail Ogulur, Yasutaka Mitamura, Duygu Yazici, Yagiz Pat, Xiangting Bu, Manru Li, Xueyi Zhu, Huseyn Babayev, Sena Ardicli, Ozge Ardicli, Paolo D'Avino, Ayca Kiykim, Milena Sokolowska, Willem van de Veen, Lukas Weidmann, Deniz Akdis, Banu Goker Ozdemir, Marie Charlotte Brüggen, Luc Biedermann, Alex Straumann, Andrea Kreienbühl, Emma Guttman‐Yassky, Alexandra F. Santos, Stefano Del Giacco, Claudia Traidl‐Hoffmann, David J. Jackson, De‐Yun Wang, Antti Lauerma, Heimo Breiteneder, Luo Zhang, Liam O'Mahony, Oliver Pfaar, Robyn O'Hehir, Thomas Eiwegger, Wytske J. Fokkens, Beatriz Cabanillas, Cevdet Ozdemir, Walter Kistler, Mahmut Bayik, Kari C. Nadeau, Maria J. Torres, Mübeccel Akdis, Marek Jutel, Ioana Agache, Cezmi A. Akdis

• The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practicallyThe prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.…