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Abstract

Background: Ultra-processed food (UPF) consumption has been linked to adverse health outcomes, including increased cancer risks. The underlying mechanisms may involve diet-induced metabolic alterations and shifts in gut microbial communities. This study aimed to use metabolomic and gut microbiome profiling to elucidate metabolic pathways and microbial signatures associated with UPF intake and determine the relevance of pathways to carcinogenic processes. Methods: Data were obtained from 800 participants of the BC Generations Project (BCGP). Dietary intake was assessed using a past year validated food frequency questionnaire (FFQ). UPF consumption was quantified as a percentage of total energy intake. Non-fasting serum samples were assayed using mass spectrometry-based metabolomic profiling, and stool samples using whole metagenome shotgun sequencing. Metabolite data were analyzed using multivariate regression, principal component analysis, and orthogonal partial least squares discriminant analysis. Microbial diversity and composition were evaluated using alpha and beta diversity metrics, differential abundance testing, and core microbiome analysis. Results: A total of 1,080 metabolites were detected, of which 68 metabolites were significantly associated with UPF consumption after adjusting for covariates (q