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Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

Background and aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis (UC) in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the five-year outcome and disease course of patients with UC in the Epi-IBD cohort. Methods: In a prospective, population-based inception cohort of unselected patients with UC patients were followed-up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. Results: A total of 717 patients were included in the study. During follow-up, 43 (6%) patients underwent a colectomy, while 163 (23%) patients were hospitalized. Of patients with limited colitis (distal to the left flexure), 90 (21%) progressed to extensive colitis. In addition, 92 (27%) patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalization (HR: 0.5 CI95% 0.3-0.8). Overall, patients were treated similarly in both geographical regions and 80 (11%) patients needed biological therapy while 210 (29%) patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalization (HR: 0.5 CI95% 0.3-0.8). Conclusions: While patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes including colectomy rates were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalization.

Background and Aims The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease [IBD]. Methods Resident memory T cells [Trm] in colonic biopsies and local antibody responses to intraepithelial microbes were analysed. Systemic antigen-specific immune T and B cell memory to a panel of commensal microbes was assessed. Results Systemically, healthy blood showed CD4 and occasional CD8 memory T cell responses to selected intestinal bacteria, but few memory B cell responses. In IBD, CD8 memory T cell responses decreased although B cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T cell function via CD39. Cognate interaction between T cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses. Conclusions A previously unrecognised imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells, rather than immunosuppression, may reinforce tissue immunity, improve barrier function, and prevent B cell dysfunction in microbiota-associated disease and IBD aetiology.