title: Of monkeys and men: a metabolomic analysis of static and dynamic urinary metabolic phenotypes in two species.
abstract: BACKGROUND
  Metabolomics has attracted the interest of the medical community for its potential in predicting early derangements from a healthy to a diseased metabolic phenotype. One key issue is the diversity observed in metabolic profiles of different healthy individuals, commonly attributed to the variation of intrinsic (such as (epi)genetic variation, gut microbiota, etc.) and extrinsic factors (such as dietary habits, life-style and environmental conditions). Understanding the relative contributions of these factors is essential to establish the robustness of the healthy individual metabolic phenotype.
  
  
  METHODS
  To assess the relative contribution of intrinsic and extrinsic factors we compared multilevel analysis results obtained from subjects of Homo sapiens and Macaca mulatta, the latter kept in a controlled environment with a standardized diet by making use of previously published data and results.
  
  
  RESULTS
  We observed similarities for the two species and found the diversity of urinary metabolic phenotypes as identified by nuclear magnetic resonance (NMR) spectroscopy could be ascribed to the complex interplay of intrinsic factors and, to a lesser extent, of extrinsic factors in particular minimizing the role played by diet in shaping the metabolic phenotype. Moreover, we show that despite the standardization of diet as the most relevant extrinsic factor, a clear individual and discriminative metabolic fingerprint also exists for monkeys. We investigate the metabolic phenotype both at the static (i.e., at the level of the average metabolite concentration) and at the dynamic level (i.e., concerning their variation over time), and we show that these two components sum up to the overall phenotype with different relative contributions of about 1/4 and 3/4, respectively, for both species. Finally, we show that the great degree diversity observed in the urinary metabolic phenotype of both species can be attributed to differences in both the static and dynamic part of their phenotype.
authors.affiliation: Laboratory of Systems and Synthetic Biology, Wageningen University and Research Center, Wageningen, The Netherlands; Biosystems Data Analysis Group, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Saccenti
authors.affiliation: Center for Magnetic Resonance (CERM), University of Florence, Florence, Italy; FiorGen Foundation, Florence, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Tenori
authors.affiliation: Synthetic Systems Biology and Nuclear Organization Group, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Verbruggen
authors.affiliation: Heymans Institute for Psychological Research Psychometrics and Statistics, University of Groningen, Groningen, The Netherlands.
authors.forename: Marieke E
authors.initials: ME
authors.lastname: Timmerman
authors.affiliation: Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek (TNO), Utrecht, The Netherlands.
authors.forename: Jildau
authors.initials: J
authors.lastname: Bouwman
authors.affiliation: Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek (TNO), Utrecht, The Netherlands; Sino-Dutch Centre for Preventive and Personalized Medicine, Utrecht, The Netherlands; Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: van der Greef
authors.affiliation: Center for Magnetic Resonance (CERM), University of Florence, Florence, Italy; Department of Chemistry, University of Florence, Florence, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.affiliation: Biosystems Data Analysis Group, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Age K
authors.initials: AK
authors.lastname: Smilde
mesh_terms: D000328:Adult; D000818:Animals; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D008253:Macaca mulatta / Q000378:metabolism*; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D019906:Nuclear Magnetic Resonance, Biomolecular; D010641:Phenotype; D014556:Urine / Q000737:chemistry*