Adherence to the Mediterranean diet assessed by a novel dietary biomarker score and mortality in older adults: the InCHIANTI cohort study

Background Dietary biomarkers may complement dietary intake assessment made by dietary questionnaires. We developed an a-posteriori dietary biomarkers score based on Mediterranean diet food groups and evaluated its association with mortality. Methods 642 participants (56% female), aged ≥65 years, with complete data on dietary biomarkers were followed during 20 years in the InCHIANTI cohort study (Tuscany, Italy). The main outcomes were all-cause, cardiovascular, and cancer mortality. Dietary biomarkers were selected from literature and from correlation analyses with dietary intakes of Mediterranean diet food groups in the study. The baseline levels of the following dietary biomarkers were chosen: urinary total polyphenols and resveratrol metabolites, and plasma carotenoids, selenium, vitamin B12, linolenic, eicosapentaenoic and docosahexaenoic acids, and the mono-unsaturated/saturated fatty acid ratio. Associations of the Mediterranean diet score using dietary biomarkers and a validated food frequency questionnaire (FFQ) (as tertiles) with mortality were assessed through Cox regression. Results During the 20-year follow-up [median (Q1–Q3), 14 (8–18) years], and 435 deaths occurred (139 from cardiovascular diseases and 89 from cancer-related causes). In the fully adjusted models, the dietary biomarker-Mediterranean diet score was inversely associated with all-cause (HRT3vs.T1 0.72; 95%CI 0.56–0.91) and cardiovascular (HRT3vs.T1 0.60; 95%CI 0.38–0.93), but not with cancer mortality. Associations between the FFQ-Mediterranean diet score and mortality were not statistically significant. Conclusions A greater adherence at baseline to a Mediterranean diet assessed by a dietary biomarker score was associated with a lower risk of mortality in older adults during a 20-year follow-up. The measurement of dietary biomarkers may contribute to guide individualized dietary counseling to older people. Trial registration NCT01331512

A Scoping Review of the Application of Metabolomics in Nutrition Research: The Literature Survey 2000–2019

Nutrimetabolomics is an emerging field in nutrition research, and it is expected to play a significant role in deciphering the interaction between diet and health. Through the development of omics technology over the last two decades, the definition of food and nutrition has changed from sources of energy and major/micro-nutrients to an essential exposure factor that determines health risks. Furthermore, this new approach has enabled nutrition research to identify dietary biomarkers and to deepen the understanding of metabolic dynamics and the impacts on health risks. However, so far, candidate markers identified by metabolomics have not been clinically applied and more efforts should be made to validate those. To help nutrition researchers better understand the potential of its application, this scoping review outlined the historical transition, recent focuses, and future prospects of the new realm, based on trends in the number of human research articles from the early stage of 2000 to the present of 2019 by searching the Medical Literature Analysis and Retrieval System Online (MEDLINE). Among them, objective dietary assessment, metabolic profiling, and health risk prediction were positioned as three of the principal applications. The continued growth will enable nutrimetabolomics research to contribute to personalized nutrition in the future.

Effects of Diet on the Microbiome and Serum Metabolome of South Asian Infants at 1 Year

Diet is known to affect the gut microbiome and metabolome composition in adults, but this has not been fully explored in infants. Dietary patterns from 1 year-old infants (n=182) from the South Asian Birth Cohort (START) study were compared to gut microbiome alpha and beta diversity and to taxa abundance differences. Diet – serum metabolite associations were identified using multivariate analysis (partial least squares-discriminant analysis, PLS-DA) and univariate analysis (T-Test). Dietary biomarkers identified from START were also examined in a separate cohort of white Caucasian infants (CHILD Cohort Study, n=82). Lastly, the association of diet with gut microbiome and serum biomarkers, considering maternal, perinatal and infant characteristics was investigated using multivariate forward stepwise regression. A dietary pattern characterized by breastfeeding, supplemented by formula and dairy was the strongest predictor of the gut microbiome that also differentiated the serum metabolome of infants. The formula and dairy dietary pattern was associated with a panel of circulating metabolites in both cohorts, including: S-methylcysteine, branched-chain/aromatic amino acids, lysine, dimethylglycine, and methionine. Breastfeeding status, the prominent feature of the dietary pattern, was also associated with a sub-set of serum metabolites in both cohorts. In START, this diet pattern was associated with the metabolites tryptophan betaine, 2-hydroxybutyric acid, tyrosine, phenylalanine, and trimethyl-N-oxide. In the CHILD Cohort Study(CHILD), breastfeeding status was associated with the metabolites aminooctanoic acid, 3-hydroxybutyric acid, and methyl-proline. The results of our study suggest that breastfeeding has the largest effect on the composition of the gut microbiome and the serum metabolome at 1 year, even when solid food diet and other covariates are considered.

Biomarkers of Dietary Patterns: A Systematic Review of Randomised Controlled Trials

Objectives We undertook a systematic review of clinical trials to identify a) dietary biomarkers being used to assess dietary pattern compliance, and b) novel biomarkers that are affected by intake of distinct dietary patterns. Methods The search strategy was developed in Medline and adapted for four additional databases: EMBASE, Cochrane CENTRAL, PreMedline, and CINAHL. Two independent reviewers extracted data and assessed risk of bias using the Cochrane tool. Results Literature search retrieved 3930 records; 450 full texts were assessed, and 30 articles reporting randomised controlled trials met the inclusion criteria. The most studied dietary patterns were the Mediterranean diet, healthy Nordic diet, Dietary Approaches to Stop Hypertension (DASH) diet, followed by low glycaemic-load diet, vegetarian diet, diets based on national and international guidelines (i.e., United Kingdom and World Health Organization Eating Guidelines), Korean diet and prudent diet. Of these, 13 articles incorporated prospectively identified dietary biomarkers, the most common being omega-3 index from erythrocytes or whole blood, 24-h urinary electrolytes, and serum or plasma carotenoids. Seventeen articles identified novel metabolomic biomarkers associated with dietary patterns, the most frequently identified being those associated with protein, lipid, and fish intakes. Conclusions Using dietary biomarkers of single nutrients, individual foods and food groups is commonly used to assess dietary compliance to dietary pattern interventions in controlled settings. However, identifying an individual's specific or broad dietary pattern, based on their biomarker profile, remains an area for future research. A framework that incorporates multiple biomarkers of individual dietary characteristics is likely necessary to accurately capture the complexity of dietary patterns. Funding Sources N/A.

Blood Metabolomic Profiling Confirms and Identifies Biomarkers of Food Intake

Metabolomics can be a tool to identify dietary biomarkers. However, reported food-metabolite associations have been inconsistent, and there is a need to explore further associations. Our aims were to confirm previously reported food-metabolite associations and to identify novel food-metabolite associations. We conducted a cross-sectional analysis of data from 849 participants (57% men) of the PopGen cohort. Dietary intake was obtained using FFQ and serum metabolites were profiled by an untargeted metabolomics approach. We conducted a systematic literature search to identify previously reported food-metabolite associations and analyzed these associations using linear regression. To identify potential novel food-metabolite associations, datasets were split into training and test datasets and linear regression models were fitted to the training datasets. Significant food-metabolite associations were evaluated in the test datasets. Models were adjusted for covariates. In the literature, we identified 82 food-metabolite associations. Of these, 44 associations were testable in our data and confirmed associations of coffee with 12 metabolites, of fish with five, of chocolate with two, of alcohol with four, and of butter, poultry and wine with one metabolite each. We did not identify novel food-metabolite associations; however, some associations were sex-specific. Potential use of some metabolites as biomarkers should consider sex differences in metabolism.

Maternal Diet and the Serum Metabolome in Pregnancy: Robust Dietary Biomarkers Generalizable to a Multiethnic Birth Cohort

ABSTRACT Background Advances in metabolomics are anticipated to decipher associations between dietary exposures and health. Replication biomarker studies in different populations are critical to demonstrate generalizability. Objectives To identify and validate robust serum metabolites associated with diet quality and specific foods in a multiethnic cohort of pregnant women. Design In this cross-sectional analysis of 3 multiethnic Canadian birth cohorts, we collected semiquantitative FFQ and serum data from 900 women at the second trimester of pregnancy. We calculated a diet quality score (DQS), defined as daily servings of “healthy” minus “unhealthy” foods. Serum metabolomics was performed by multisegment injection-capillary electrophoresis-mass spectrometry, and specific serum metabolites associated with maternal DQSs were identified. We combined the results across all 3 cohorts using meta-analysis to classify robust dietary biomarkers (r > ± 0.1; P < 0.05). Results Diet quality was higher in the South Asian birth cohort (mean DQS = 7.1) than the 2 white Caucasian birth cohorts (mean DQS <3.2). Sixty-six metabolites were detected with high frequency (>75%) and adequate precision (CV <30%), and 47 were common to all cohorts. Hippuric acid was positively associated with healthy diet score in all cohorts, and with the overall DQS only in the primarily white Caucasian cohorts. We observed robust correlations between: 1) proline betaine—citrus foods; 2) 3-methylhistidine—red meat, chicken, and eggs; 3) hippuric acid—fruits and vegetables; 4) trimethylamine N-oxide (TMAO)—seafood, meat, and eggs; and 5) tryptophan betaine—nuts/legumes. Conclusions Specific serum metabolites reflect intake of citrus fruit/juice, vegetables, animal foods, and nuts/legumes in pregnant women independent of ethnicity, fasting status, and delays to storage across multiple collection centers. Robust biomarkers of overall diet quality varied by cohort. Proline betaine, 3-methylhistidine, hippuric acid, TMAO, and tryptophan betaine were robust dietary biomarkers for investigations of maternal nutrition in diverse populations.