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

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Title: Determinants of the urinary and serum metabolome in children from six European populations
Authors: Lau, CH
Siskos, AP
Maitre, L
Robinson, O
Athersuch, TJ
Want, EJ
Urquiza, J
Casas, M
Vafeiadi, M
Roumeliotaki, T
McEachan, RRC
Azad, R
Haug, LS
Meltzer, HM
Andrusaityte, S
Petraviciene, I
Grazuleviciene, R
Thomsen, C
Wright, J
Slama, R
Chatzi, L
Vrijheid, M
Keun, HC
Coen, M
Item Type: Journal Article
Abstract: Background Environment 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). Methods Metabolic 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). Results We 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-deoxyerythronic 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. Conclusions We 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.
Issue Date: 8-Nov-2018
Date of Acceptance: 10-Oct-2018
URI: http://hdl.handle.net/10044/1/65436
DOI: https://dx.doi.org/10.1186/s12916-018-1190-8
ISSN: 1741-7015
Publisher: BioMed Central
Journal / Book Title: BMC Medicine
Volume: 16
Copyright Statement: © 2018 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Commission of the European Communities
Medical Research Council (MRC)
Funder's Grant Number: 308333
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Exposome metabolomics
Metabolic phenotyping
Birth cohorts
NMR spectroscopy
European children
Metabolic profile
11 Medical And Health Sciences
Publication Status: Published
Article Number: 202
Appears in Collections:Department of Surgery and Cancer