Pathways of Epithelial Barrier Breakdown and Remodeling in Esophageal Organoids by Commonly Used Surfactants

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BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by symptoms of esophageal dysfunction, such as dysphagia and food impaction, as well as eosinophilic inflammation and impaired epithelial barrier integrity, which promotes allergen influx. Environmental exposures that weaken the esophageal barrier, including surfactants found in personal care products such as sodium dodecyl sulfate (SDS) and cocamidopropyl betaine (CAPB), have been proposed as contributors to disease susceptibility. However, their direct effects on esophageal epithelial barrier function and associated molecular responses remain insufficiently characterized. METHODS: We investigated the molecular and functional consequences of SDS and CAPB exposure in primary EoE-derived esophageal organoids and air-liquid interface cultures derived from biopsy tissue samples. We conducted transepithelial electrical resistance (TEER) measurements, paracellular flux assays, RNA sequencing, targeted and untargeted proteomics, and immunofluorescence imaging. RESULTS: Treatment of esophageal organoids with SDS or CAPB (0-100 μg/mL) caused dose-dependent cytotoxicity and barrier disruption, with SDS producing stronger effects. At 12.5 μg/mL, viability declined to ~30% with SDS versus ~60% with CAPB, accompanied by greater TEER reduction and ~2-fold higher permeability. RNA-seq of organoids exposed to 12.5 μg/mL for 24 h showed distinct transcriptomic clustering, with 2749 shared and > 1500 surfactant-specific differentially expressed genes, indicating broad epithelial remodeling, cell-cycle suppression, and stress responses, more pronounced under SDS. SDS preferentially activated inflammatory and innate immune pathways, which was supported by proteomic detection of elevated cytokines (TNF, IL-8, IL-18, etc.). Both surfactants induced keratinization, epidermal cell differentiation, and partial epithelial-mesenchymal transition signatures, including increased vimentin without E-cadherin loss. CONCLUSION: These findings demonstrate that common surfactants can induce coordinated epithelial stress responses in esophageal tissue models and may act as environmental aggravating factors in EoE at relatively low doses. This work underscores the need to consider mucosal exposure to consumer product ingredients in the context of epithelial barrier disorders, particularly surfactants such as SDS and CAPB, and supports efforts to refine formulations to minimize epithelial damage.

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