Epithelial Barrier Theory
 | It has been suggested that this article be merged into Innate immune system#Anatomical barriers. (Discuss) Proposed since September 2025. |
| Epithelial barrier theory | |
|---|---|
| Specialty | Immunology, Allergy, Dermatology, Gastroenterology |
| Symptoms | Variable; associated with asthma, atopic dermatitis, food allergy, autoimmune disease, metabolic syndrome |
| Complications | Chronic inflammation |
| Causes | Environmental exposures, pollutants, detergents, food additives, microplastics |
| Risk factors | Industrialization, urbanization, modern lifestyle factors |
| Prognosis | Not applicable |
| Frequency | Unknown |
The epithelial barrier hypothesis (also known as the epithelial barrier theory) is a medical concept suggesting that dysfunction of epithelial barriers, induced by environmental toxic substances such as air pollutants, detergents, food additives, microplastics, and nanoparticles, contributes to the development of chronic diseases. Barrier impairment occurs in the skin, respiratory tract, and intestines, and is often accompanied by microbial dysbiosis, bacterial translocation, tissue and systemic inflammation, and immune dysregulation. These processes have been proposed as contributing factors to allergic, autoimmune, metabolic, and neuropsychiatric disorders.[1][2]
The hypothesis was initially framed in the early 2020s by immunologist Cezmi A. Akdis and has since been discussed in independent peer-reviewed reviews in the fields of immunology, allergy, dermatology, and nutrition.[3][4]
Background
[edit]Akdis introduced the concept to explain the rising prevalence of chronic inflammatory diseases in industrialized societies. It builds on earlier frameworks such as the hygiene hypothesis and incorporates findings from microbiome research.[5]
Proposed mechanisms
[edit]Barrier damage
[edit]Environmental exposures including ozone, particulate matter, detergents, and synthetic particles may impair epithelial junctions, increasing permeability and allowing antigens to penetrate underlying tissues.[6]
Microbial dysbiosis
[edit]Barrier impairment can alter microbiota composition in the skin, gut, and airways, reducing microbial diversity and promoting overgrowth of opportunistic species.[7]
Immune activation
[edit]Cytokines such as interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) are implicated in initiating type 2 inflammatory responses following barrier disruption.[8]
Disease contexts
[edit]- Allergic diseases: asthma, atopic dermatitis, food allergy, allergic rhinitis, eosinophilic esophagitis.[9]
- Autoimmune and metabolic disorders: type 1 diabetes, multiple sclerosis, metabolic dysfunction-associated steatotic liver disease (MASLD).[9]
- Neuropsychiatric conditions: preliminary research suggests possible links to neuroinflammatory disorders such as Alzheimer’s disease.[9]
Independent reviews
[edit]Independent peer-reviewed coverage includes:
- Ferraro et al. (2025) in Nutrients, reviewing associations with food allergy.[3]
- Patel & Lio (2024) in Journal of Integrative Dermatology, providing a systematic review of mechanisms.[4]
Reception and criticism
[edit]Supporters highlight the hypothesis as a unifying framework in chronic inflammatory disease research. Critics argue that many associations remain correlative and emphasize the need for longitudinal human studies and standardized methods to assess epithelial barrier integrity.[10][11]
See also
[edit]References
[edit]- ^ Akdis, Cezmi A (2021). "Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?". Nature Reviews Immunology. 21 (11): 739–751. doi:10.1038/s41577-021-00538-7. PMID 33846604.
- ^ Sozener, ZC (2022). "Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease". Allergy. 77 (5): 1418–1449. doi:10.1111/all.15240. PMC 9306534. PMID 35108405.
- ^ a b Ferraro, VA (2025). "The Epithelial Barrier Hypothesis in Food Allergies: The State of the Art". Nutrients. 17 (6): 1014. doi:10.3390/nu17061014. PMC 11994808. PMID 40290033.
- ^ a b Patel, K (2024). "Epithelial barrier hypothesis: A systematic review". Journal of Integrative Dermatology. 4 (1): 1–15. doi:10.1002/jiderm.127482 (inactive 3 September 2025).
{{cite journal}}: CS1 maint: DOI inactive as of September 2025 (link) - ^ Sozener, ZC (2022). "The External Exposome and Allergies: From the Perspective of the Epithelial Barrier Hypothesis". Frontiers in Allergy. 3 (12) 887672. doi:10.3389/falgy.2022.887672. PMC 9285408. PMID 35855646.
- ^ Lu, HF (2024). "Involvement and repair of epithelial barrier dysfunction in allergic diseases". Frontiers in Immunology. 15 1348272. doi:10.3389/fimmu.2024.1348272. PMC 10867171. PMID 38361946.
- ^ Canani, RB (2024). "Skin, gut, and lung barrier: Physiological interface and target of intervention for preventing and treating allergic diseases". Allergy. 79 (6): 1485–1500. doi:10.1111/all.16092. PMID 38439599.
- ^ Duchesne, M (2022). "Epithelial cell alarmin cytokines: Frontline mediators of the asthma inflammatory response". Frontiers in Immunology. 13 975914. doi:10.3389/fimmu.2022.975914. PMC 9616080. PMID 36311787.
- ^ a b c Na, S (2024). "The epithelial barrier theory and its associated diseases". Allergy. 79 (12): 3192–3237. doi:10.1111/all.16318. PMC 11657050. PMID 39370939.
- ^ Shin, W (2018). "Intestinal barrier dysfunction orchestrates the onset of inflammatory host-microbiome cross-talk in a human gut inflammation-on-a-chip". Proceedings of the National Academy of Sciences USA. 115 (45): E10539 – E10547. Bibcode:2018PNAS..11510539S. doi:10.1073/pnas.1810819115. PMC 6233106. PMID 30348765.
- ^ Furman, D (2019). "Chronic inflammation in the etiology of disease across the life span". Nature Medicine. 25 (12): 1822–1832. doi:10.1038/s41591-019-0675-0. PMC 7147972. PMID 31806905.