title: The impact of micronutrient status on health: correlation network analysis to understand the role of micronutrients in metabolic-inflammatory processes regulating homeostasis and phenotypic flexibility.
abstract: BACKGROUND
  Vitamins and carotenoids are key micronutrients facilitating the maintenance of health, as evidenced by the increased risk of disease with low intake. Optimal phenotypic flexibility, i.e., the ability to respond to a physiological challenge, is an essential indicator of health status. Therefore, health can be measured by applying a challenge test and monitoring the response of relevant phenotypic processes. In this study, we assessed the correlation of three fat-soluble vitamins, (i.e., vitamin A or retinol, vitamin D3, two homologues of vitamin E) and four carotenoids (i.e., α-carotene, β-carotene, β-cryptoxanthin, and lycopene), with characteristics of metabolic and inflammatory parameters at baseline and in response to a nutritional challenge test (NCT) in a group of 36 overweight and obese male subjects, using proteomics and metabolomics platforms. The phenotypic flexibility concept implies that health can be measured by the ability to adapt to a NCT, which may offer a more sensitive way to assess changes in health status of healthy subjects.
  
  
  RESULTS
  Correlation analyses of results after overnight fasting revealed a rather evenly distributed network in a number of relatively strong correlations per micronutrient, with minor overlap between correlation profiles of each compound. Correlation analyses of challenge response profiles for metabolite and protein parameters with micronutrient status revealed a network that is more skewed towards α-carotene and γ-tocopherol suggesting a more prominent role for these micronutrients in the maintenance of phenotypic flexibility. Comparison of the networks revealed that there is merely overlap of two parameters (inositol and oleic acid (C18:1)) affirming that there is a specific biomarker response profile upon NCT.
  
  
  CONCLUSIONS
  Our study shows that applying the challenge test concept is able to reveal previously unidentified correlations between specific micronutrients and health-related processes, with potential relevance for maintenance of health that were not observed by correlating homeostatic measurements. This approach will contribute to insights on the influence of micronutrients on health and help to create efficient micronutrient intervention programs.
authors.affiliation: Netherlands Institute for Applied Science (TNO), Research Group Microbiology & Systems Biology, Zeist, The Netherlands.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: van den Broek
authors.affiliation: Netherlands Institute for Applied Science (TNO), Research Group Microbiology & Systems Biology, Zeist, The Netherlands.
authors.forename: Bas H A
authors.initials: BHA
authors.lastname: Kremer
authors.affiliation: Netherlands Institute for Applied Science (TNO), Research Group Microbiology & Systems Biology, Zeist, The Netherlands.
authors.forename: Marisa
authors.initials: M
authors.lastname: Marcondes Rezende
authors.affiliation: Netherlands Institute for Applied Science (TNO), Research Group Microbiology & Systems Biology, Zeist, The Netherlands.
authors.forename: Femke P M
authors.initials: FPM
authors.lastname: Hoevenaars
authors.affiliation: DSM Nutritional Products, Analytical Research Centre and Human Nutrition and Health Department, Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Weber
authors.affiliation: DSM Nutritional Products, Analytical Research Centre and Human Nutrition and Health Department, Basel, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hoeller
authors.affiliation: Netherlands Institute for Applied Science (TNO), Research Group Microbiology & Systems Biology, Zeist, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: van Ommen
authors.affiliation: Netherlands Institute for Applied Science (TNO), Research Group Microbiology & Systems Biology, Zeist, The Netherlands.
authors.forename: Suzan
authors.identifier: 0000-0001-9612-657X
authors.initials: S
authors.lastname: Wopereis
keywords: Carotenoids; Glucose; Inflammation; Lipid; Metabolic challenge test; Phenotypic flexibility; Systems biology; Vitamins