Dairy intake in two American cohorts associates with novel and known targeted and untargeted circulating metabolites

Authors: HRUBY, ADELA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DENNIS, COURTNEY - Broad Institute Of Mit/harvard; JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2020
Publication Date: 2/13/2020
Citation: Hruby, A., Dennis, C., Jacques, P.F. 2020. Dairy intake in two American cohorts associates with novel and known targeted and untargeted circulating metabolites. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa021.
DOI: https://doi.org/10.1093/jn/nxaa021

Interpretive Summary: Metabolomics is the study of the thousands of byproducts, called metabolites, in the body. Metabolites can be found in every tissue, but most commonly they are studied in either the blood (called "circulating metabolites") or urine. In this study, we wanted to know how many and which metabolites differ between people who consume high amounts versus little or no dairy, and different dairy product types, including milk, yogurt, cheese, and cream and butter. We evaluated the metabolite-dairy relationships in two large groups of middle-aged Americans who participated in the Framingham Heart Study. They reported their food intake, including dairy, by completing a questionnaire. Their blood was drawn and analyzed for metabolites using sophisticated processes, which identified many hundreds of metabolites by name ("known" metabolites) as well as many thousands of metabolites whose identities are unknown. We then compared these metabolites against dairy intake. We found that a handful of known metabolites differed between people who consumed dairy (including milk, cheese, yogurt, and cream/butter) and those who didn't. Moreover, there were several dozen metabolites that appeared to differ between people who consume yogurt and those who don't. Many of these appeared to be dairy fatty acids as well as food flavorings or additives, although these are suggested identities and would need further confirmation. In sum, this research was able to show that there are specific metabolites that appear associated with dairy consumption. This work contributes to the growing field of nutritional metabolomics, as well as the search for valid markers of dairy consumption.

Technical Abstract: Background: The role of dairy in human health may be elucidated by investigating circulating metabolites associated with intake. Objective: To identify metabolites associated with quantity and type of dairy intake in the Framingham Heart Study Offspring (N=2,205) and Third Generation (Gen3; N=866) cohorts. Methods: Dairy intake (total dairy, milk, cheese, yogurt, and cream/butter) was analyzed in relation to targeted (Offspring, 217 signals; Gen3, 79 signals) and untargeted metabolites (Gen3, ~7,031 signals) in 2:1 discovery:validation subsets. Orthogonal projections to latent structures with discriminant analysis (OPLS-DA) was used to identify metabolites distinguishing between high and low intake. Linear regression in validation subsets was used to confirm putative associations, subsequently tested in the total samples. Previously reported associations were also investigated. Results: OPLS-DA in Offspring targeted discovery subset resulted in variable importance in projection (VIP) >1 of 65, 60, 58, 66, and 60 metabolites for total dairy, milk, cream/butter, cheese, and yogurt, respectively, of which 5, 3, 1, 6, and 4 metabolites, respectively, remained after adjustment. In Gen3 targeted discovery subset, OPLS-DA resulted in VIP>1 of 17, 15, 13, 7, and 6 metabolites for total dairy, milk, cream/butter, cheese, and yogurt, respectively. In Gen3 untargeted discovery subset, OPLS-DA resulted in VIP>2 signals of 203, 503, 78, 186, and 206 metabolites, respectively. Combining subsets and targeted and untargeted results in Gen3, significant associations of 7 (6 unannotated), 2, 12 (11 unannotated), 0, and 61 (all unannotated) metabolites, respectively, remained after adjustment. Candidate identities of unannotated signals included fatty acids, food flavorings, and additives. Results supported relationships previously reported for C14:0 sphingomyelin, and marginal associations for deoxycholates. Conclusions: Dairy intake associated with numerous circulating metabolites, including long-chain fatty acids, pantothenate, uridine, and sphingomyelins. Reports about diet-metabolite relationships and validation of previous findings may be limited by specificity of dietary intake and breadth of measured metabolites.