Abstract
BACKGROUND: There is increasing evidence that diets characterized by food biodiversity could contribute to health outcomes. Greater dietary species diversity has been linked to reduced gastrointestinal cancer risk and all-cause mortality. However, mechanistic pathways supporting the association between food biodiversity and health are just beginning to be explored. AIM: To characterize the metabolic profile associated with food biodiversity of diets in a pan-European population. METHODS: Dietary species richness (DSR), or the absolute number of unique species in an individual's diet, was calculated for 7,983 cancer-free control participants within the European Prospective Investigation into Cancer and Nutrition cohort study. Usual dietary intakes in the preceding year were assessed at recruitment with country-specific dietary questionnaires. Metabolomic profiles from blood which included 128 circulating endogenous metabolites,32 polyphenol compounds, and 39 fatty acid isomers were used as biomarkers of potential mechanisms underlying nutrition and health associations. Lasso regression identified key metabolites in discovery and replication sets, and multivariable stepwise linear regression were used to quantify associations between DSR and metabolomic profiles. RESULTS: A total of 52 metabolites were selected using Lasso regression in the replication set, of which 70% were statistically significant in stepwise linear regression. Higher DSR was associated with lower levels of 4 amino acids (e.g., tyrosine, -0.0231, 95% CI: -0.0362, -0.0100, p = 0.0009) and 2 acylcarnitines (e.g., C14:2, -0.0834, 95% CI: -0.1084, -0.0583, p < 0.0001). Conversely, higher levels were observed for 7 amino acids (e.g., tryptophan, -0.0954, 95% CI: -0.1049, -0.0860, p < 0.0001) and 9 polyphenols (e.g., epicatechin, p = 0.0017). CONCLUSION: In this European middle-aged adult population, the circulating metabolic profiles of biodiverse diets are consistent with the metabolome linked with health-promoting diets, indicating metabolite groups that provide metabolic homeostasis, anti-inflammatory, anti-oxidative stress, and anti-obesogenic properties. These findings support the health benefits of consuming more diverse dietary species and may partially explain the inverse associations found in relation with mortality or gastrointestinal cancer.