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 multi-ethnic cohort of pregnant women. Design In this cross-sectional analysis of 3 multi-ethnic Canadian birth cohorts, we collected semi-quantitative food frequency questionnaires (FFQ) and serum 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 diet quality scores 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 two 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 multi-ethnic populations.

Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods

“…27 studies were considered for this review [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. Their major features such as study design, methodology used for TMAO determination, and the effects of foods on TMAO are given in Table 1 .…”

“…15 studies evaluated the possible relationship between fish and TMAO. 13 studies demonstrated that levels of urinary or plasma TMAO and/or TMA are significantly associated with the intake of fish [ 11 , 12 , 20 , 21 , 24 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 36 ]. One of the earliest studies evaluated 46 different foods and demonstrated that only fish and other sea-products significantly increase urinary TMAO [ 12 ].…”

“…17 studies that assessed the correlation between egg consumption and increased TMAO were evaluated. Robust correlations between TMAO and eggs were demonstrated in six studies [ 13 , 14 , 19 , 25 , 30 , 34 ]. Pignanelli et al [ 25 ] described that the intake of egg yolk contributes significantly to plasma levels of TMAO.…”

“…12 studies [ 12 , 17 , 20 , 21 , 26 , 27 , 28 , 30 , 31 , 34 , 35 , 36 ] evaluated the possible correlation between meat consumption and an increase of TMAO. Seven studies showed that the levels of urinary or plasma TMAO and/or TMA are significantly associated with the intake of meat.…”

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

“…These foods were chosen because they have been widely used to characterize healthy dietary patterns (i.e., prudent diet) that reduce chronic disease risk [35–42]. Our DQS correlates well with a modified version of the AHEI previously derived in these cohorts [20,34,43]. The infant semi-quantitative FFQ built upon existing instruments used in 3 studies: the Avon Longitudinal Study of Parents and Children (ALSPAC) [44], the Born in Bradford (BiB) study [45], and the Study of Health Assessment and Risk Evaluation (SHARE) [30].…”