Determinants of the urinary and serum metabolome in children from six European populations

Abstract

BackgroundEnvironment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment–health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project (http://www.projecthelix.eu).MethodsMetabolic phenotypes of matched urine and serum samples from 1192 children (aged 6–11) recruited from birth cohorts in six European countries were measured using high-throughput 1H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit).ResultsWe identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythreonic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum.ConclusionsWe have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1190-8) contains supplementary material, which is available to authorized users.

Combined Markers to Assess Meat Intake—Human Metabolomic Studies of Discovery and Validation

“…In urine, creatine has been reported in intervention studies where meat was provided for 1–2 weeks, individually or as part of a high‐meat diet . Urinary creatine was also associated with meat intake in a cross‐sectional study in children; in adults, it was only associated with meat fat, but not with red meat, processed meats or fish, although it has been reported after intake of fish and shellfish . In the present studies, creatine is excreted shortly after a single serving of meat, peaking at 2 h for pork and chicken, and at 4 h for beef, after which its excretion gradually decreases.…”

The Urinary Metabolome of Healthy Newborns

“…This is often not fully realized, due to the fact that the majority of clinical studies that have been published are for adults [49][50][51][52][53][54][55]. Indeed, to date, there have only been a few comprehensive studies looking at age-specific intervals in children [48,56,57] and newborns [30].…”

Characterization of bulk phosphatidylcholine compositions in human plasma using side-chain resolving lipidomics

“…AbsoluteIDQ TM p150 and p180 kits have emerged as established measurement kits for quantification of phospholipids, such as PCs, in blood from thousands of participants in large epidemiological cohorts (11,12,15,16,20,(35)(36)(37)(38)(39) and in projects using a variety of human and non-human sample matrices (40)(41)(42)(43)(44). As the kits quantify PCs on the level of lipid species, each PC measure is composed of isobaric PCs (within mass resolution) with different combinations of fatty acid chain lengths and degrees of desaturation for the two residues.…”