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Cezmi A. Akdis, MD
Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Davos
Humans are exposed to a variety of toxins and chemicals every day. It is estimated that more than 350’000 new chemicals have been introduced to our lives after 1960s, mostly without any reasonable control of their health effects. There is a plethora of studies pointing to the rapid rise of exposure to many of these harmful substances during the last six decades with their implications on skin and mucosal epithelial barrier functions. According to the epithelial barrier theory (www.epithelialbarriertheory.com), exposure to many of these substances damages the epithelium on the surface of our skin, lungs and intestine. A defective epithelial barrier has been demonstrated in more than 70 diseases, including allergic and autoimmune conditions such as asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, celiac disease, and inflammatory bowel disease. In addition, leakiness of the gut epithelium is also implicated in systemic autoimmune and metabolic conditions such as diabetes, obesity, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and autoimmune hepatitis. Finally, distant inflammatory responses due to a ‘leaky gut barrier’ and microbiome changes are suspected in Alzheimer’s disease, Parkinson’s disease, chronic depression and autism spectrum disorders. The “epithelial barrier theory” proposes that the rise in epithelial barrier damaging agents linked to industrialization, urbanization and modern life underlies the rise in allergic, autoimmune and other chronic conditions. After breaking of the epithelial barriers by various environmental agents and infections, microbiome which normally floats above the skin and mucosas goes deeper between and beneath the epithelial barrier. Microbial dysbiosis and decreased biodiversity develop following the colonization of opportunistic pathogens. An “epithelitis” with the release of alarmins and multiple chemokines initiates the immune response and inflammation inside and beneath the epithelium with the aim of “expulsion response” to deeper and dysbiotic microbiome and pollutants and toxic substances reaching to deeper tissues, because of epithelial barrier defects. Oxidative stress, endoplasmic reticulum stress and protein folding defects, mitochondrial stress, DNA repairy delay and failures, and innate immune response have been identified as key mechanisms of tissue injury and inflammation. Cells and cytokines leak to the circulation from the barrier defective tissues and cause inflammation in target tissues in distant organs as repeatedly demonstrated in diabetes, rheumatoid arthritis and multiple sclerosis experimental models and patients. Disturbed epithelial barrier healing capacity because of microbial dysbiosis, chronic tissue inflammation and epigenetic mechanisms lead to the chronicity of the disease.
03.04.2025, 13:30 - 14:30 Uhr
Bibliothek des IRM-UZH (Y52 E 28/24)
Die Fortbildungen sind für alle IRM-Mitarbeitenden und ausgewählte Externe (Angehörige von Polizei und Justiz) offen
