Metabolomic pattern of ultraprocessed food intake and its association with colorectal cancer risk.

[BACKGROUND] High ultra-processed food (UPF) intake has been linked to colorectal cancer (CRC), but underlying mechanisms remain unclear.

[OBJECTIVE] To evaluate a metabolomic pattern of UPF intake and its association with CRC risk.

[DESIGN] Integrating food frequency questionnaire data and high-throughput metabolomic profiling in 1740 participants (mean age at blood draw: 59.9 years; >95% non-Hispanic white participants) from nested case-control studies within the Nurses' Health Study and Health Professionals Follow-up Study, we derived and validated a UPF-related metabolomic pattern as a weighted sum of metabolites selected via elastic net regression with 10-fold cross-validation. We evaluated prospective associations of this pattern and individual metabolites with CRC risk using multivariable conditional logistic regression in 686 pairs of incident CRC cases and matched controls.

[RESULTS] Among 222 metabolites, we constructed a UPF metabolomic pattern comprising 50 metabolites, primarily lipids and amino acids, with 22 positively and 28 inversely associated with total UPF intake (pattern vs intake: Spearman rho=0.35). The pattern was associated with higher CRC risk (highest vs lowest quintile: OR (95% CI) 1.71 (1.15 to 2.53), p value trend=0.002). Correlations of individual metabolites with UPF intake were moderately aligned with their associations with CRC risk (rho=0.50). N2, N2-dimethylguanosine, a marker of meat/poultry intake, was positively associated with CRC risk (1.96 (1.27 to 3.03)), while 21-deoxycortisol, related to cortisol biosynthesis, was inversely associated (0.59 (0.41 to 0.86)).

[CONCLUSION] We developed a UPF metabolomic pattern. The pattern and several metabolites were associated with CRC risk, providing biological insights into potential pathways underlying the UPF-CRC relationship.