Of Monkeys and Men: A Metabolomic Analysis of Static and Dynamic Urinary Metabolic Phenotypes in Two Species

Abstract

BackgroundMetabolomics 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.MethodsTo 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.ResultsWe 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.

Hypothesis: The Sound of the Individual Metabolic Phenotype? Acoustic Detection of NMR Experiments

“…It is substantially different from the clustering experiment, which is an unsupervised pattern recognition test where no reference was given to the listeners who were asked to group the audio signals on the basis of some inherent similarity. The audio classification test mimicked indeed what is typically done in metabolomics studies when using supervised statistical analysis (Assfalg et al, 2008;Bernini et al, 2009;Saccenti et al, 2014).…”

“…The present study analyzed data from previous material (Assfalg et al, 2008;Bernini et al, 2009;Saccenti et al, 2014). As deliberated by the Ethical Committee of the Area Vasta Toscana-Tuscany Health Centre (Prot.…”

“…The donors were four healthy males, randomly selected from a cohort of 31 young adults; samples were collected during previously reported studies in which up to 40 urine samples were collected on consecutive days (Assfalg et al, 2008;Bernini et al, 2009;Saccenti et al, 2014). In the first set of experiments two donors were considered: four urine samples for each donor, taken from the first data collection, were used in the clustering test.…”

Proof of concept for quantitative urine NMR metabolomics pipeline for large-scale epidemiology and genetics

“…We used this approach here but it would be relevant to test this assumption with forthcoming data in extensive epidemiological cohorts by evaluating and comparing multiple methods, e.g., normalisation to the sum of all or selected metabolites in the sample, and potential new methods. 14,15 Serum samples (n=5,788) from NFBC66 were analysed using a high-throughput quantitative NMR metabolomics platform originating from our team. 7 This platform provides simultaneous quantification of routine lipids and lipid concentrations of 14 lipoprotein subclasses and major subfractions, and further quantifies abundant fatty acids, amino acids, ketone bodies and gluconeogenesis-related metabolites in absolute concentration units.…”

Hochdurchsatz‐Metabolomik mit 1D‐NMR

“…Einer der wichtigsten Befunde der Metabolomik ist, dass jedes Individuum “chemisch verschieden” von allen anderen ist, wenn man die Zusammensetzung der niedermolekularen Substanzen in den systemischen biologischen Flüssigkeiten wie Urin, Blut oder Speichel betrachtet . Unsere Arbeitsgruppe hat entscheidend dazu beigetragen, diese starke chemische Signatur zu definieren und zu charakterisieren, die nun individueller metabolischer Phänotyp oder Metabotyp genannt wird . Im Urin, einer biologischen Flüssigkeit, deren Zusammensetzung starken täglichen Schwankungen unterliegt, konnte ein unveränderlicher Teil des humanen metabolischen Phänotyps, der für jedes Individuum charakteristisch ist, durch multivariate statistische Analyse verschiedener Proben, die an unterschiedlichen Tagen genommen wurden, nachgewiesen werden.…”