Abstract
Cholelithiasis is a common, costly gastrointestinal disease with a rising global prevalence, and diet-related inflammation is closely associated with the onset of cholelithiasis. The energy-adjusted dietary inflammatory index (E-DII) provides a robust measure of dietary inflammatory potential by accounting for total energy intake, but prospective data on its link to cholelithiasis in general populations remain scarce. We explored this association in a large prospective cohort of 202,129 adults aged 40-69 from the UK Biobank. E-DII scores were derived from 24-h dietary recall data, and Cox regression models were used to examine associations between E-DII quartiles and cholelithiasis. Restricted cubic spline (RCS) regression characterized nonlinear relationships, with subgroup and sensitivity analyses (competing risk models, propensity score matching) validating findings. In fully adjusted model, the hazard ratios (HRs) with 95% confidence intervals (CIs) for cholelithiasis across higher E-DII quartiles were 1.05(0.97, 1.12), 1.00 (0.93, 1.08) and 1.19 (1.11, 1.28) compared to the lowest quartile, respectively. The RCS analysis showed a nonlinear and positive association between E-DII and cholelithiasis. Risk increased when E-DII was below −1.891, decreased slightly from −1.891 to −0.507, and increased continuously after −0.507. Subgroup and sensitivity analyses largely corroborated the primary findings, indicating robustness of the observed associations. No association was observed between E-DII and cholelithiasis-related mortality. In this large prospective cohort study, higher E-DII scores were associated with an increased risk of cholelithiasis, exhibiting a nonlinear pattern. These findings suggest that dietary adjustment may be beneficial for cholelithiasis prevention and warrant further targeted research.</p>