The Dietary Biomarkers Development Consortium: An Initiative for Discovery and Validation of Dietary Biomarkers for Precision Nutrition

Abstract

Diet is a complex exposure that affects health across the lifespan. Objective biomarkers that can reliably reflect intake of nutrients, foods, and dietary patterns with sufficient accuracy are an important tool for assessing associations of diet with health outcomes. Advances in metabolomics, coupled with feeding trials and high-dimensional bioinformatics analyses, pave the way for discovering compounds that can serve as sensitive and specific biomarkers of dietary exposures. The Dietary Biomarkers Development Consortium (DBDC) is leading the first major effort to improve dietary assessment through the discovery and validation of biomarkers for foods commonly consumed in the United States diet. To achieve this goal, a 3-phase approach will be implemented to identify, evaluate, and validate food biomarkers. In phase 1, 3 controlled feeding trial designs will be implemented by administering test foods in prespecified amounts to healthy participants, followed by metabolomic profiling of blood and urine specimens collected during the feeding trials to identify candidate compounds. Data from these studies will characterize the pharmacokinetic parameters of candidate biomarkers associated with specific foods. In phase 2, the ability of candidate biomarkers to identify individuals eating the biomarker-associated foods will be evaluated using controlled feeding studies of various dietary patterns. In phase 3, the validity of candidate biomarkers to predict recent and habitual consumption of specific test foods will be evaluated in independent observational settings. Data generated during all study phases will be archived in a publicly accessible database as a resource for the research community. The DBDC aims to significantly expand the list of validated biomarkers of intake for foods consumed in the United States diet, which can help advance understanding of how diet influences human health. This manuscript discusses the DBDC's organizational infrastructure, study design, laboratory methods, and strategies for dietary biomarker discovery and validation.

Trial registration number: This trial was registered at Phase 1 Seattle Dietary Biomarkers Development Center (P1-SDBDC) as NCT05580653, at Fruit and Vegetable Biomarker Discovery (UCD-DBDC) as NCT05621863, and at Dietary Biomarkers Intervention Core as NCT05616585.

Keywords: consortium; dietary biomarkers; dietary exposures; food chemistry; metabolomics.

FIGURE 1

Dietary Biomarkers Development Consortium organizational structure. DSMB, Data Safety Monitoring Board; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; USDA-ARS, USDA-Agricultural Research Service; USDA-NIFA, USDA-National Institute of Food and Agriculture.

FIGURE 2

Dosing scheme of each food for determination of biomarkers during phase 1 in the Dietary Biomarkers Development Consortium–Davis study design. Participants will be provided a test meal consisting of either zero dose, a medium dose (1 half-cup equivalent), or a high dose (2 half-cup equivalent) of the indicated fruit and vegetable. Test meals will be prepared using other foods (for example, chicken broth, milk, etc.) that will not interfere with the biomarker determination to create an acceptable product for consumption. In brackets are gram-weight equivalents of corresponding raw food.

FIGURE 3

Study design at Dietary Biomarkers Development Consortium at Harvard.

FIGURE 4

Study design at Dietary Biomarkers Development Consortium–Fred Hutch. PK, pharmacokinetic; HEI, Healthy Eating Index.

FIGURE 5

Study design at Dietary Biomarkers Development Consortium–Davis. A total of 280 healthy subjects from the Davis and Sacramento areas in California will be enrolled in this study, which is divided into 3 phases. In phase 1, 30 participants will undergo a randomly assigned crossover dietary intervention involving 3 meal challenges with varying levels of fruits and vegetables for breakfast (refer to Figure 1 for dosing schemes). In phase 2, 50 participants will be stratified and randomly assigned into 3 dietary groups: 1) typical American diet (TAD), consisting of 10 participants receiving a diet devoid of target foods (bananas, peaches, strawberries, tomatoes, green beans, and carrots); 2) TAD+, involving 20 participants, includes the same diet as TAD but incorporates low levels of the target fruits and vegetables; 3) Dietary Guidelines for Americans (DGA), also including 20 participants, offers a diet enriched with higher levels of fruits and vegetables, including the target foods. Phase 3 involves a cross-sectional study with 200 participants who will provide dietary data and biological samples.