Potential approaches in repairing the damaged epithelial barrier in eosinophilic esophagitis

Eosinophilic esophagitis, or short EoE, is a chronic, food- and aeroallergen-driven type 2 inflammation strongly linked to epithelial barrier dysfunction, causing dysphagia and food impaction. We discuss the key question of whether barrier damage initiates the disease by allowing allergen penetration across the epithelium, or whether epithelial disruption results secondarily from inflammation.

This review examines current evidence of structural and functional epithelial defects in EoE, including abnormalities in junctional proteins, impaired cell differentiation, and increased permeability, based on a literature search in PubMed and Google Scholar. These defects stem from environmental or dietary exposures in individuals with genetic susceptibility, as evidenced by genome-wide association studies that identify genes crucial for epithelial structure and regulation. It also assesses the extent to which barrier dysfunction is caused by inflammatory cytokines, especially IL-13 and other type 2 cytokines, which directly alter epithelial architecture. Lastly, we explore emerging strategies to strengthen or repair the epithelial barrier, ranging from dietary interventions and biologics to approaches targeting epithelial metabolism, protease balance, and hormonal pathways.

Maintaining epithelial integrity is essential for preventing and treating EoE. Future treatments should directly reinforce the epithelial barrier, unlike current treatment options that reduce type 2 inflammation.