There has been a steep increase in allergic and autoimmune diseases, reaching epidemic
proportions and now affecting more than one billion people worldwide. These diseases
are more common in industrialized countries, and their prevalence continues to rise
in developing countries in parallel to urbanization and industrialization. Intact
skin and mucosal barriers are crucial for the maintenance of tissue homeostasis as
they protect host tissues from infections, environmental toxins, pollutants and allergens.
A defective epithelial barrier has been demonstrated in allergic and autoimmune conditions
such as asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, eosinophilic
esophagitis, coeliac 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' and microbiome changes are suspected in Alzheimer disease,
Parkinson disease, chronic depression and autism spectrum disorders. This article
introduces an extended 'epithelial barrier hypothesis', which proposes that the increase
in epithelial barrier-damaging agents linked to industrialization, urbanization and
modern life underlies the rise in allergic, autoimmune and other chronic conditions.
Furthermore, it discusses how the immune responses to dysbiotic microbiota that cross
the damaged barrier may be involved in the development of these diseases.