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, 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.