The epithelial barrier theory proposes a comprehensive explanation for the origins of allergic and other chronic noncommunicable diseases.

The epithelial barrier theory proposes that modern environmental exposures compromise skin and mucosal surfaces, initiating local inflammation that propagates systemically. The theory integrates epidemiological trends, molecular mechanistic data, and emerging clinical data to show how everyday exposures cause the development and exacerbation of more than 70 chronic noncommunicable diseases. A canonical epithelial cell and barrier injury cascade takes place, generating oxidative stress with increased reactive oxygen species, the release of alarmins, and multiple chemokines and epithelial barrier disruption. The damage to epithelial barriers occurs together with microbial dysbiosis. The alerted immune system fuels various immune activation loops involving multiple cells and chemokines and links barrier leakiness to atopic, autoimmune, metabolic, and neuropsychiatric disease clusters. Supporting the one health concept, abundant exposure of domestic animals and pets to the same groups of toxic substances related to their diseases has recently become more evident. The prevalence of these preventable diseases showed an increase in parallel to industrialization and modernization and epidemiologic exposure to culprit substances throughout the whole world, with a substantial public health burden reaching trillions of dollars each year. Impact statement Modern environmental exposures compromise epithelial barriers, triggering inflammation, microbial dysbiosis, and chronic disease clusters-atopic, autoimmune, metabolic, neuropsychiatric. These preventable conditions now affect millions and impose a public health and economic burden of trillions annually in healthcare costs and lost productivity.