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

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

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

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.

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)).

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.