Association of healthy lifestyle, metabolic alterations and lower mortality risk of IBD patients: a prospective cohort and mediation analysis.

BACKGROUND: Limited evidence has investigated the effect of a healthy lifestyle on mortality in patients with inflammatory bowel disease (IBD). We aimed to assess the relationship between a healthy lifestyle and all-cause mortality in IBD, as well as the underlying metabolic mechanisms in a prospective cohort. METHODS: Overall, 5052 IBD patients free of cancer (aged 57.0±8.0 years, 48.5% men) were included from UK Biobank cohort. A healthy lifestyle was defined as a normal body mass index, never smoking, moderate alcohol consumption, regular physical activity, adequate sleep duration and healthy diet. The primary outcome was all-cause mortality. Lifestyle-related metabolic signatures were constructed by linear regression and elastic net regression in patients with metabolomics data. A multivariable Cox proportional hazards model was used to assess associations between lifestyle, metabolic signature and all-cause mortality. The mediation effect of lifestyle-related metabolic signatures was estimated through the Cox marginal structural model. RESULTS: During a median of 14.6 years' follow-up, 583 deaths were identified. Compared with unfavourable lifestyle, those with favourable lifestyle showed significantly lower risk of all-cause mortality in IBD (HR=0.56, 95% CI 0.46 to 0.68), ulcerative colitis (UC) (HR=0.61, 95% CI 0.48 to 0.79) and Crohn's disease (HR=0.49, 95% CI 0.36 to 0.67), and 18.9% of the reduced risk was mediated by metabolic signature. Metabolic signature was significantly associated with lower all-cause mortality, with HR of 0.65 (95%CI 0.49 to 0.85) for values above versus below the median and 0.73 (95%CI 0.64 to 0.83) for per SD increase. Subgroup and sensitivity analyses demonstrated similar results. CONCLUSION: A healthy lifestyle is associated with lower mortality in IBD patients. This beneficial effect may be mediated by metabolic signatures and related to favourable metabolic alterations.