Impact of Surfactants in Oral Care Products on Epithelial Cell Activation and Barrier Dysfunction in Eosinophilic Esophagitis

Introduction: Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition characterized by esophageal inflammation and tissue remodeling driven by type 2 immune responses, with both genetic predispositions and environmental factors, including dietary allergens and irritants, implicated in its pathogenesis. Surfactants such as sodium dodecyl sulfate (SDS/SLS) and cocamidopropyl betaine (CAPB), which are commonly found in oral care products, may contribute to esophageal epithelial barrier dysfunction. This study aimed to compare the effects of SDS and CAPB on epithelial integrity and immune responses in cells and organoids derived from EoE patients. Methods: Esophageal biopsy samples from five EoE patients were used to generate organoids, and SDS (12.5 μg/mL) and CAPB (12.5 μg/mL), at doses relevant to human exposure, were applied on day 11. RNA samples were collected after 24 hours for sequencing, while targeted proteomic analyses were performed on supernatants collected after 48 hours. In parallel, air–liquid interface (ALI) cultures were treated with the same compounds, and epithelial barrier integrity was assessed using transepithelial electrical resistance (TER) and FITC-dextran permeability assays. Results: Both SDS and CAPB significantly disrupted epithelial barrier function within 48 hours, with SDS exerting a more pronounced effect. Proteomic analysis revealed key alterations in proteins associated with cellular metabolism and immune responses, including ADGRG1, NECTIN2, CES2, and TGF-alpha. RNA sequencing demonstrated extensive transcriptional changes, with 7,234 genes affected by SDS and 7,461 genes affected by CAPB. A shared set of 2,560 upregulated and 2,360 downregulated genes indicated common mechanisms, particularly involving pathways related to autophagy, cell growth, epithelial differentiation, keratinization, and lipid metabolism. In addition, pathways related to the cellular response to unfolded proteins and mast cell activation were upregulated, and key oxidative stress–related genes, including PRDX5, DUOX1, DUOX2, and SOD2, showed increased expression. SDS more strongly affected pathways involved in keratinocyte differentiation and digestive system development. Conclusions: These findings demonstrate that commonly used surfactants such as SDS and CAPB, at doses relevant to everyday exposure, can significantly disrupt esophageal epithelial integrity and alter immune responses, with SDS showing a stronger disruptive effect on epithelial barrier function and associated molecular pathways, underscoring the potential for oral care products containing these surfactants to exacerbate EoE by impairing epithelial barriers and promoting pro-inflammatory responses.