Determinants of the urinary and serum metabolome in children from six European populations
Creators
- Lau, Chung-Ho E.1
- Siskos, Alexandros P.1
- Maitre, Léa2
- Robinson, Oliver3
- Athersuch, Toby J.1
- Want, Elizabeth J.1
- Urquiza, Jose2
- Casas, Maribel2
- Vafeiadi, Marina4
- Roumeliotaki, Theano4
- McEachan, Rosemary R. C.5
- Azad, Rafaq5
- Haug, Line S.6
- Meltzer, Helle M.6
- Andrusaityte, Sandra7
- Petraviciene, Inga7
- Grazuleviciene, Regina7
- Thomsen, Cathrine6
- Wright, John5
- Slama, Remy8
- Chatzi, Leda9
- Vrijheid, Martine2
- Keun, Hector C.10
- Coen, Muireann1
- 1. Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, SW7 2AZ, UK
- 2. ISGlobal, Barcelona, Spain
- 3. MRC-PHE Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, London, W2 1PG, UK
- 4. Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece
- 5. Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
- 6. Norwegian Institute of Public Health, Oslo, Norway
- 7. Department of Environmental Sciences, Vytautas Magnus University, Kaunas, Lithuania
- 8. Inserm, Univ. Grenoble Alpes, CNRS, IAB (Institute of Advanced Biosciences), Grenoble, France
- 9. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA
- 10. Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W12 0NN, UK
Description
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.
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