A population-based nationwide study on total colectomy for ulcerative colitis and risk of ten prevalent inflammatory or autoimmune diseases

Background: There is growing evidence to support a role of the gut microbiome in the development of chronic inflammatory and autoimmune disease (IAD). We used total colectomy (TC) for ulcerative colitis (UC) as a model for a significant disruption in gut microbiome to explore an association with subsequent risk of IAD. Methods: We identified all patients with UC and no diagnosis of IAD prior to their UC diagnosis in Denmark from 1988 to 2015. Patients were followed from the date of UC to a diagnosis of IAD, death or end of follow-up, whichever occurred first. We used Cox regression to estimate hazard ratios (HRs) of IAD associated with TC, adjusting for age, sex, Charlson Comorbidity Index, and calendar year of UC diagnosis. Results: 30,507 patients with UC (3,155 with TC and 27,352 without) were identified from the Danish National Patient Registry. During 43,266 person-years of follow-up, 2733 patients were diagnosed with an IAD. The risk of any IAD was higher for patients with TC compared to patients without (adjusted HR [aHR] 1.39 (95% CI: 1.24–1.57)). When the analyses were adjusted for exposure to antibiotics, immunomodulatory medicine and biologics (covering 2005–2018), the risk of IAD was still higher for patients with total colectomy (aHR = 1.41 (95% CI: 1.09;1.83)). Disease-specific analyses were weakened by a low number of outcomes. Conclusions: The risk of IAD was higher for patients who underwent TC for UC compared to patients who did not. KEY MESSAGES: What is already known? oThe gut microbiome plays an important role in host immune homeostasis, and changes in gut bacterial diversity and composition may change the individual’s risk of inflammatory and autoimmune disease (IAD). What is new here? oPatients with ulcerative colitis who undergo total colectomy have a higher risk of being diagnosed with IAD, compared to patients with ulcerative colitis who do not undergo total colectomy. How can this study help patient care? oFuture research can help uncover the mechanisms responsible for the higher risk of certain IADs after total colectomy. If the microbiome plays a role, modifying the gut microbiome could prove a viable therapeutic strategy to reduce the risk of developing IADs.