Epithelial Barrier Theory in Lectures and Slides

Exposure to barrier damaging agents or genetic deficiency in barrier molecules cause colonization of opportunistic pathogens and epithelial inflammation. Microbiome migrates deeper inside the epithelium and gets in contact with basal epithelial cells and stimulates the immune system. Opportunistic pathogens, such as S aureus, Moraxella, Haemophilus, Pneumococcus are colonized and translocate beneath the epithelium. An Immune response develops against the commensals and opportunistic pathogens and leads to the development of microbial dysbiosis. Microbial dysbiosis and the translocation of commensals and opportunistic pathogens across epithelial barriers typically intiates a type 2 immune response, characterized by a predominance of TH2 cells, ILC2s and eosinophils. The aim here is to expulse the microbes that are going deeper between and even below the epithelium. The epithelium cannot fully repair and close the barrier, instigating a vicious circle of leaky barriers, microbial dysbiosis and chronic inflammation.

The relatively recent onset of the epidemics of allergic, autoimmune and metabolic conditions leads to the question what might underlie their development. A prominent hypothesis is the hygiene hypothesis, which proposes that certain microorganisms protect against inflammatory diseases, and that their loss, due to hygiene measures, results in an increase in allergy, asthma and autoimmunity. Several extensions to the hygiene hypothesis have been proposed. One is the ‘old friends’ hypothesis’, which suggests that some microbial species have co-evolved with humans and their surrounding animals and have protective functions. Several shortcomings of the hygiene hypothesis have been discussed during the last decades and suggest that these hypothesis do not fully explain the rise in allergic and autoimmune disease. These include the fact that water sanitation was established in many western cities in the 1920s, but allergy and asthma epidemics only started in the 1960s. The protective role of parasite infections that increase biodiversity has been questioned for the same reason. In addition, allergic asthma is still on the rise in some cities in Asia and Africa that have low standards of hygiene. Another limitation of the hygiene hypothesis and biodiversity hypothesis is that probiotics are not viable alternatives for the prevention or treatment of allergies. Moreover, studies of migrants who move from developing countries to affluent regions demonstrate a rapid increase in asthma and allergic diseases as well as autoimmune diseases, such as type 1 diabetes and multiple sclerosis. It appears that domestic living conditions, increased birth by ceserian sections, antibiotic usage, dietary practices, urbanization, indoor air pollution are more prominent factors compared to general public hygiene.