Phenotypic flexibility in nutrition research to quantify human variability: building the bridge to personalised nutrition

Phenotypic flexibility is a methodology that accurately assesses health in terms of mechanistic understanding of the interrelationship of multiple metabolic and physiological processes. This starts from the perspective that a healthy person is better able to cope with changes in environmental stressors that affect homeostasis compared to people with a compromised health state. The term 'phenotypic flexibility' expresses the cumulative ability of overarching physiological processes to return to homeostatic levels after short-term perturbations. The concept of phenotypic flexibility to define biomarkers for nutrition-related health was introduced in 2009 in the area of health optimisation and prevention and delay of non-communicable disease. The core approach consists of the combination of imposing a challenge test to the body followed by time-resolved analysis of multiple biomarkers. This new approach may better facilitate nutritional health research in intervention studies since it may show effects on early derailed physiological markers and the biomarker response can be extended by perturbing the system, thereby making them more sensitive in detecting health effects from food and nutrition. At the same time, interindividual variation can also be extended and compressed by challenge tests, facilitating the bridge to personalised nutrition. This review will overview where the science is in this research arena and what the phenotypic flexibility potential is for the nutrition field.