Metabolomic Profiling and Diet Quality Scoring in a Randomized Crossover Trial of Healthy and Typical Dietary Patterns.

This randomized cross-over feeding trial aimed to identify objective metabolomic biomarkers of dietary patterns and assess their relationship with cardiometabolic health. Metabolomic responses were compared between two distinct dietary patterns: the Healthy Australian Diet (HAD) based on national guidelines, and the Typical Australian Diet (TAD) reflecting apparent population intake. Thirty-four healthy adults were provided with all food for each diet pattern for 2 weeks, separated by a washout period. Plasma and spot urine samples were collected pre-post-intervention, and metabolomic profiling was performed using UHPLC-MS/MS. Elastic net regression identified 65 discriminatory metabolites (31 plasma, 34 urine) that distinguished HAD from TAD. A composite diet quality biomarker score derived from these metabolites, was significantly associated with improved cardiometabolic markers, including reductions in systolic and diastolic blood pressure, LDL-cholesterol, triglycerides, and fasting glucose. Several metabolites identified aligned with known food-specific biomarkers, while others represent novel candidates. Distinct short-term metabolomic signatures of a healthy dietary pattern were observed across biofluids. The identified candidate metabolites and biomarker score have potential for translation into objective tools for assessing diet quality in line with the Australian Dietary Guidelines and for early cardiometabolic risk monitoring, pending external validation in independent cohorts. Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id = 384710.