Work

Barrier dysfunction in allergic diseases: Mechanisms, diagnosis, and therapeutic targeting

Year: 2026

Type: article

Abstract: Background The rising prevalence of allergic diseases parallels increasing environmental factors that compromise epithelial barrier integrity. The “epithelial barrier hypothesis” has evolved, emphasizing that dysfunction of skin, gut, and airway epithelia can act as an early event contributing to allergic sensitization and comorbidity. Objective This review synthesizes recent advances elucidating how barrier defects facilitate allergen passage, promote type 2 immunity, and contribute to the atopic march and atopic multimorbidity involving atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR), which may follow multiple trajectories. Methods We critically reviewed literature on barrier dysfunction in AD, FA, asthma, and AR, focusing on mechanisms, diagnostic biomarkers, and therapeutic interventions. Results Distinct organ-specific mechanisms were identified: filaggrin deficiency and Staphylococcus aureus protease activity in AD; zonulin-associated tight junction opening and IL-13-driven epithelial changes in FA; virus-induced oxidative stress and air-pollution–mediated barrier impairment in asthma; and allergen protease–mediated tight junction disruption in AR. Sequential and overlapping barrier defects may contribute to the atopic march and allergic comorbidities. Barrier-related tools, including transepidermal water loss (TEWL), the lactulose/mannitol (L/M) ratio, nasal TEWL (nTEWL), and epithelial sampling-based assays, are increasingly used to assess epithelial integrity, although their clinical maturity differs across organs. Therapeutic strategies include emollients, microbiome-based interventions, allergen immunotherapy (AIT), and biologics, but direct barrier-restoring evidence remains variable. Conclusion Integrating barrier assessment into clinical or translational evaluation and targeting barrier repair alongside anti-inflammatory therapy may provide new opportunities for modifying allergic disease trajectories and managing allergic comorbidities.

Source: Allergy medicine.

DOI: 10.1016/j.allmed.2026.100141

Authors: Weichun Xiao, Shan Wang, Ailin Tao

Institutions: Second Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou Medical University

Language: English

Topic: Dermatology and Skin Diseases

Subfield: Dermatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,300