Figure 2
Pathogenetic events as mechanisms of the epithelial barrier theory: A cascade of events play a role in the pathogenesis of diseases associated with the epithelial barrier theory and development of many chronic noncommunicable diseases. Direct toxicity to epithelium and microbes: Genetic defects in barrier-related molecules or exposure to epithelial barrier-damaging agents cause a disruption of the skin and mucosal tight junction barriers and may also show a direct toxicity to health-promoting commensal microbes. Epithelitis and microbial dysbiosis: It is followed by translocation of microbiota to inter and subepithelial areas and colonization of opportunistic pathogens, such as Staphylococcus aureus (S. aureus), Moraxella catarrhalis, Haemophilus influenzae and pneumococcus bacteria. It is associated with microbial dysbiosis and decreased biodiversity of commensal bacteria. Epithelitis starts with the release of multiple alarmins. Expulsion response: An immune response develops towards commensals and opportunistic pathogens in the gut and respiratory system, and systemic inflammation takes place. Decreased biodiversity takes place because of loss of commensals and colonizing opportunistic pathogens. Migration of inflammatory cells to distant organs: Chronic inflammation in the subepithelial area prevails as one of the main reasons for the development of chronic diseases in the affected tissues. Distant organs are affected because of circulating microinflammation and migration of activated immune system cells to distant organs. Epigenetic regulation and chronicity: An impaired ability to restore the epithelial barrier function due to inflammation and epigenetic changes instigates a vicious cycle of leaky barriers, microbial dysbiosis and chronic inflammation.
Figure 1
The increase in the prevalence and exacerbations of many allergic, autoimmune, metabolic and neurodegenerative diseases was associated with damage to the epithelial layer induced by exposure to infections agents, allergens, particulate matter, diesel exhaust, cigarette smoke, laudry and dishwasher detergents and rinse aids, household cleaners, toothpastes, microplastics, nanoparticles, ozone, processed food additives and emulsifiers and other unidentified chemical substances. Some of these substances may have synergistic effects in the damage of epithelial barriers. Leaky barriers allow the passage of allergens, pollutants, toxins and microbes.
Why are allergies increasing? (Keymechanisms)
1. Damage to epithelial barriers
Modern exposures weaken the protectivebarriers of:
- Skin
- Airways
- Gut
This allows allergens and microbes topenetrate more easily and activate the immune system.Main culprits include:
- Air pollution (PM2.5, ozone, diesel exhaust)
- Detergents and cleaning chemicals (e.g., SLS)
- Food additives (emulsifiers, preservatives) Microplastics and industrial chemicals.
👉 This is the core idea behind the epithelial barrier theory.
2. Microbiome disruption (dysbiosis)
- Loss of beneficial bacteria
- Overgrowth of opportunistic microbes
Causes:
- Antibiotics
- Processed diets
- Reduced contact with nature
This impairs immune tolerance and promotes allergy.
3. Urbanization and lifestyle changes
- Less exposure to diverse microbes (“biodiversity loss”)
- Indoor lifestyles with poor air quality
- Increased hygiene and chemical exposure
4. Dietary changes
- High sugar, low fiber diets
- Ultra-processed foods
These affect gut barrier integrity andimmune regulation.
5. Early-life exposures
- C-section birth
- Reduced breastfeeding
- Early antibiotic use
These alter immune development and increaseallergy risk.
6. Climate change and environmentalstress
- Longer pollen seasons
- Increased allergen potency
- More air pollution
🧠Bigpicture
Allergies are not just genetic—they arelargely driven by environment–immune system interactions.👉 Thekey shift since the 1960s: Humans began living in a chemically intense,low-microbial, highly urban environment
