Plasma Phospholipids and Incident Ulcerative Colitis: A Prospective Cohort Study in the UK Biobank

Objective: To investigate the association between plasma levels of total phospholipids in lipoprotein particles and the risk of incident ulcerative colitis (UC). Methods: This prospective cohort study analyzed data from 254,921 participants in the UK Biobank (2006-2020), excluding those with pre-existing UC or missing data. Phospholipid levels were measured via nuclear magnetic resonance spectroscopy. Cox proportional hazards models were adjusted for demographic, lifestyle, socioeconomic, and genetic factors. Dose-response and subgroup analyses were conducted using generalized additive models. Results: During a median follow-up duration of 15.78 years, 1,330 incident UC cases were identified. Higher phospholipid levels demonstrated a significant inverse association with UC risk. After full adjustment, each unit increase in phospholipids was associated with a 16% lower risk (HR 0.84, 95% CI 0.75-0.95, p=0.006). Quartile analyses showed lower risks in higher quartiles, with the risk reduction most evident by the third quartile and then generally stable (Q4 vs Q1: HR 0.83, 95% CI 0.71-0.97, p=0.020). Generalized additive and quartile analyses suggested a non-linear plateau/threshold pattern rather than a strictly linear association. Subfraction analyses showed heterogeneous associations, with inverse patterns mainly observed for phospholipids carried by HDL, IDL, and LDL particles, whereas chylomicron- and several VLDL-related phospholipids showed null or positive/non-protective associations. Conclusion: Higher plasma total phospholipid levels are independently associated with reduced UC risk, suggesting phospholipid metabolism may play a protective role in UC pathogenesis. However, this association is not uniform across lipoprotein subfractions. These findings highlight potential metabolic biomarkers and mechanistic pathways requiring further validation for UC prevention.