Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease of the gastrointestinal (GI) tract, comprised of two main subcategories: ulcerative colitis (UC) and Crohn’s disease (CD) [1]. With increasing rates in newly industrialized and westernized countries, IBD presents a growing public health challenge [2], [3]. It affects greater than 0.3% of the global population, with the highest prevalence rates in Europe and North America [2]. In the UK alone, approximately 640,000 individuals were estimated to have an IBD diagnosis in 2017, with predictions of an 11% increase by 2025 [4]. IBD often leads to acute complications and severe chronic conditions, posing life-threatening risks and potentially reducing life expectancy [5], [6], [7]. Despite current treatment strategies providing temporary relief, their effectiveness in managing long-term symptoms is limited, and some treatments may lead to severe health conditions, including certain cancers [8], [9].

Previous studies have reported inconsistent findings regarding the association between UC or CD and overall and cause-specific mortality [10], [11], [12], [13], [14], [15], [16], [17]. While most recent prospective cohort studies reported elevated mortality risks in both UC and CD patients, others found no significant differences in outcomes compared with individuals without IBD [11], [18], [19], [20]. Such inconsistencies could be attributable to the limitations of each study, including small sample sizes, limited ability to control for confounders particularly for registry data, and population differences. Meanwhile, previous studies have linked IBD to increased mortality from GI disease, infection, respiratory conditions such as chronic obstructive pulmonary disease, and cardiovascular disease (CVD) [21], [22], [23]. Understanding the cause-specific mortality associated with IBD is essential for shaping future prevention and management efforts, including potential screening and surveillance strategies, thereby potentially improving outcomes for IBD patients.

Our study leveraged the substantial data available from the UK Biobank cohort, a large, population-based, prospective cohort study with long-term follow-up for mortality and extensive data on possible confounders and effect modifiers [24], [25]. We aimed to evaluate the association of IBD with all-cause mortality and mortality from major causes of death, including CVD, respiratory disease, and cancer, and determine whether specific demographic, lifestyle, or other medical factors modify the association between IBD and all-cause mortality.