Spondyloarthritis (SpA), a rheumatic disease characterised by inflammation affecting the axial skeleton and/or peripheral joints, is frequently accompanied by intestinal inflammation and dysbiosis. However, the epithelial contribution to host–microbiota interactions remains poorly defined. This thesis aims to establish patient-derived epithelial models to investigate properties associated with inflammatory diseases and responses to inflammatory and microbial signals. We have developed a cӕcal organoid platform from healthy controls and patients with SpA and/or inflammatory bowel disease (IBD), integrating culture-medium quality control, expansion, cryopreservation and differentiation. Organoids contain several differentiated epithelial cell populations and display polarised organisation. Their adaptation into monolayers on Transwell inserts enables separate access to the apical and basolateral surfaces and is accompanied by increasing transepithelial electrical resistance during culture. Differentiated models respond to a TNFα/IL-1β/IL-6 cytokine cocktail through changes in chemokine and epithelial defence gene expression. These changes display distinct profiles according to exposure duration and the gene examined. In monolayers, exposure to IL-17A and TNFα increases CCL20, NOS2 and DUOX2 expression relative to unstimulated controls. Apical butyrate exposure modifies selected inflammatory parameters. The tested Mediterraneibacter gnavus preparations do not induce a detectable inflammatory response within the transcriptional panel and conditions examined. We have compared isolated crypts from 41 participants, unstimulated organoids from 32 donor-derived lines and cytokine-exposed organoids from 30 lines by RNA-seq, across healthy controls, Crohn’s disease, SpA without IBD and SpA with IBD. In crypts, Crohn’s disease differs from controls through 1,728 differentially expressed genes (FDR < 0.05) and an inflammatory profile partially concordant with independent epithelial datasets from the literature. This profile differs markedly in unstimulated organoids: 22 of the 25 transcriptional signatures representing biological processes (Hallmark) significant in both contexts show opposite enrichment directions. For SpA without IBD, only 6 genes differ significantly from controls in crypts, yet 37 of the 50 Hallmark gene sets show significant enrichment, negative for inflammatory responses and oxidative phosphorylation and positive for the cell cycle. In this group, profiles remain concordant between crypts and organoids, with or without cytokine exposure. Paired analysis, restricted to organoid lines with matched unstimulated and cytokine-exposed samples, identifies 7 programmes whose changes between conditions differ between SpA and controls, mainly involving metabolism, cellular stress and the cell cycle. Finally, IBD × SpA interaction analysis identifies 495 genes whose expression in participants with both diagnoses deviates from that expected from the profiles associated with each disease considered independently.This thesis establishes a platform to investigate intestinal epithelial responses in SpA. SpA-associated transcriptional programmes remain concordant between isolated crypts and organoids, whereas Crohn-associated programmes diverge. Limited sample sizes constrain the interpretation and scope of these comparisons. Confirmation of SpA signatures in an independent cohort and functional validation are required to relate these epithelial response programmes to the dysregulated environment.