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

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• dc.contributor.author Lau, Chung-Ho E.
• dc.contributor.author Maitre, Léa
• dc.contributor.author Urquiza, José M.
• dc.contributor.author Casas Sanahuja, Maribel
• dc.contributor.author Vrijheid, Martine
• dc.contributor.author Coen, Muireann
• dc.date.accessioned 2020-01-15T10:22:31Z
• dc.date.available 2020-01-15T10:22:31Z
• dc.date.issued 2018
• dc.description.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-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. 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.
• dc.description.sponsorship This research received funding from the EU European Commission’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 308333—the HELIX project. We would like to thank all the study participants and the full list of the HELIX Project Investigators that can be found at http://www.projecthelix.eu. The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), NIH/NINDS (grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1). Dr. Maribel Casas received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00128).
• dc.format.mimetype application/pdf
• dc.identifier.citation Lau CE, Siskos AP, Maitre L, Robinson O, Athersuch TJ, Want EJ et al. Determinants of the urinary and serum metabolome in children from six European populations. BMC Med. 2018;16(1):202. DOI: 10.1186/s12916-018-1190-8
• dc.identifier.doi http://dx.doi.org/10.1186/s12916-018-1190-8
• dc.identifier.issn 1741-7015
• dc.identifier.uri http://hdl.handle.net/10230/43288
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof BMC Medicine. 2018;16(1):202
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
• dc.rights © The Author(s). 2018 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Birth cohorts
• dc.subject.keyword Epidemiology
• dc.subject.keyword European children
• dc.subject.keyword Exposome metabolomics
• dc.subject.keyword LC-MS
• dc.subject.keyword Metabolic phenotyping
• dc.subject.keyword Metabolic profile
• dc.subject.keyword Metabonomics
• dc.subject.keyword NMR spectroscopy
• dc.subject.keyword Paediatrics
• dc.title Determinants of the urinary and serum metabolome in children from six European populations
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion