Eosinophilic Oesophagitis (EoE) is a chronic allergen-mediated disease of the oesophagus with a rising incidence which represents an increased clinical burden associated with disease. During EoE chronic inflammation, eosinophils and other leukocytes migrate into the oesophageal epithelium and consume available oxygen at a higher rate than the surrounding epithelium. This reduction in the oxygen tension places an increased metabolic demand on the epithelium and induces an extended inflammatory hypoxia in the EoE oesophagus. Previous studies showed that this extended hypoxic microenvironment is concordant with a decrease in HIF-1α signaling, whereby HIF-1α was repressed in active EoE and shown to regulate the barrier forming tight junction claudin-1. Pharmacologic HIF�1α stabilisation restored the HIF-1α/claudin-1 regulatory axis and highlighted the barrier protective role of HIF-1α in the oesophageal epithelium. With reference to upstream regulators associated with oesophageal epithelial reactive changes, microRNAs (miRNAs) were an attractive avenue of exploration which were previously researched in EoE, however their impact on the oesophageal epithelium has not been fully elucidated. Previous research has defined a coordinate negative feedback loop with the elevation of miR-155 and the destabilisation of HIF-1α signaling in response to extended experimental hypoxia, however the functional impacts of miR-155 in the oesophagus had not yet been fully identified. Using in silico analyses we highlight an enrichment of miR-155 regulated pathways within the EoE transcriptome and suggest the action of miR-155 in hypoxic pathways and epithelial barrier regulation. Furthermore, we show via in situ hybridisation an elevation in miR-155 in oesophageal biopsies of active EoE patients, whereby miR-155 was shown localised to basal and suprabasal layers of the epithelium. In concordance with the literature, we defined an elevation of miR-155 in EPC2-hTERTs cultured in extended experimental hypoxia, which was inversely correlated with the decrease in HIF�1α signaling. Using miR-155 stably overexpressing (miR-155OE) EPC2-hTERTs we reported a dysfunctional epithelial barrier in 3-dimensional physiologic cultures measured by transepithelial electrical resistance (TEER). qRT-PCR and western blot analysis identified a selective decrease in claudin-7, with immunofluorescence staining further confirming a decrease in expression and mislocalisation of claudin-7. In silico analysis did not identify miR-155 binding sites in claudin-7 mRNA, however we propose that miR-155 induces dysfunctional epithelial barrier through indirect attenuation of claudin-7. Molecular characterisation studies have shown a dysregulation in the basal-stem cell compartment in the EoE epithelium. Studies have highlighted a decrease in CD73 and CD104 expressing basal-stem cells in response to EoE inflammation which was associated with reduced epithelial renewal. Further studies have also associated an elevation in quiescent progenitorstem cells in EoE pathology, however the impact of miR-155 on the epithelial basal-stem compartment has not been fully explored. We identified that miR-155OE cultures have an acute elevation of proliferation and basal stem markers, followed by a reduction at extended timepoints. This was concordant with reduction in suprabasal keratin-13 and keratin-4, and elevation in late-differentiation markers keratin�16 and involucrin. We propose that miR-155 is associated with destabilisation of CD73, dysregulates other basal stem-like cells and induces an accelerated maturation phenotype in organoid cultures. Collectively, these findings suggest that miR-155 is an epithelial miRNA elevated in EoE pathology. MiR-155 elevation is concordant with the extended hypoxic microenvironment and attenuation in HIF�1α, moreover we highlight that miR-155 impairs barrier integrity by the indirect attenuation of claudin-7 which may contribute to EoE pathophysiology. MiR-155 elevation was also associated with the decrease in basal CD73, and in the induction of an accelerated maturity phenotype characterised by an atrophy of adequate stratification processes indictive of EoE pathology.