Better biomarkers for health and nutrition
Diet, foods and food components are prime environmental factors affecting the transcriptome, proteome and metabolome. This life-long interaction largely defines an individual’s health or disease state. The body’s adaptive capacity to alterations in dietary conditions is called phenotypic flexibility and is key to the maintenance of overall homeostasis and consequently, health and healthy ageing. Given that health can be considered as the ability to adapt to daily stressors, new biomarkers are needed to quantify the body’s ability to adequately absorb a variety of perturbations and regain homeostasis. Consequently, biomarkers should not quantify homeostasis but rather the stress-response curve after such a perturbation, namely it is important to quantify the ability to adapt. The EU-funded NUTRITECH project used cutting-edge technologies such as genomics, transcriptomics, proteomics, metabolomics and laser scanning cytometry to measure homeostasis and phenotypic flexibility. Extending the concept of metabolic flexibility To date nutrition research has largely been focused on determining the effects of nutrient and non-nutrient food components on gene and protein expression and metabolic outcomes. NUTRITECH built on the foundations of conventional nutrition research using cutting-edge analytical methods to comprehensively evaluate the diet-health relationship. Researchers quantified the effect of diet on phenotypic flexibility, based on metabolic flexibility. NUTRITECH though extended the notion of flexibility to all underlying physiological processes and cell and genetic mechanisms involved in absorbing metabolic challenges and that are essential to maintaining optimal metabolic and inflammatory health. ‘Biomarkers thus report on the mechanisms that retain optimal stress responses after a metabolic/caloric challenge,’ says project coordinator Ben van Ommen. The aim was to show that using caloric restriction as an intervention should demonstrate a change in phenotypic flexibility. Based on this, the researchers conducted an extensive dietary intervention study on 72 volunteers that aimed to reduce the food intake by 20 % over a 12-week period. Phenotypic flexibility was measured by applying a dietary challenge containing high levels of carbohydrates, fat and proteins. The response profiles of numerous classical and novel biomarkers were then assessed over a period of several hours after the challenge was consumed. Scientists obtained important insight into the flexibility status of the intestines, pancreas, liver, certain muscles and adipose tissue by applying a standard glucose tolerance test and quantifying the response of insulin, and hundreds of other metabolites and proteins. The project also focused on the maintenance of DNA integrity to oxidative stress, developing new methods to measure the maintenance of genome integrity, which examined how well participants can safeguard the DNA in the genome. A laser scanning cytometry protocol for scoring micronuclei was also created to identify damage to chromosomes and the mitotic spindle apparatus. Personalised nutrition approach Volunteers appeared to respond differently to the same treatment due to differences in genetic background, body composition and eating patterns. For example, magnetic resonance imaging data showed that fat content and distribution differentiated amongst male and female participants. This allowed NUTRITECH to accurately measure how people react differently to the same dietary changes using a biochemical map of homeostasis. ‘Results suggest that it is important to get up close and personal when substantiating health effects, ’ says Mr Ommen. The phenotypic flexibility biomarkers have raised considerable interest in the food industry. NUTRITECH also gave rise to the launch of another project that involved five renowned food companies. Both projects aim to exploit the outcomes of the NUTRITECH intervention study by adopting a more personalised nutrition approach in an upcoming intervention study.
Keywords
NUTRITECH, biomarkers, phenotypic flexibility, homeostasis, intervention study