A scheme for a flexible classification of dietary and health biomarkers

Abstract

Biomarkers are an efficient means to examine intakes or exposures and their biological effects and to assess system susceptibility. Aided by novel profiling technologies, the biomarker research field is undergoing rapid development and new putative biomarkers are continuously emerging in the scientific literature. However, the existing concepts for classification of biomarkers in the dietary and health area may be ambiguous, leading to uncertainty about their application. In order to better understand the potential of biomarkers and to communicate their use and application, it is imperative to have a solid scheme for biomarker classification that will provide a well-defined ontology for the field. In this manuscript, we provide an improved scheme for biomarker classification based on their intended use rather than the technology or outcomes (six subclasses are suggested: food compound intake biomarkers (FCIBs), food or food component intake biomarkers (FIBs), dietary pattern biomarkers (DPBs), food compound status biomarkers (FCSBs), effect biomarkers, physiological or health state biomarkers). The application of this scheme is described in detail for the dietary and health area and is compared with previous biomarker classification for this field of research.

Keywords: Biomarker; Classification; Effect; Exposure; Metabolomics; Nutrition; Ontology; Review; Susceptibility.

Fig. 1

Interactions between the environment and a biological system. The system can be any organism or group of inter-dependent organisms and the environmental exposure can be any changes of the environment. The image in a applies to the static part of susceptibility and in b applies to the variable part of susceptibility. (a) Basic relationship between exposures, effects in a biological system and the susceptibility factors characteristic of the system. Susceptibility is basically an effect modifier for how the exposure(s) affect the biological response. (b) The effect imposed upon the biological system may eventually change the system characteristics thereby changing its susceptibility. (c) The exposure of the system may also be directly affected by the system susceptibility factors themselves, e.g. if exposure is avoided or exacerbated (e.g. if the sensation of hunger is increased so food intake increases beyond needs)

Fig. 2

Diversity of interaction between the biological system with intrinsic system variables and the surrounding environmental variables. Both exposures (environmental variables) and their corresponding host susceptibility factors (intrinsic variables) are diverse in nature and the steady state level of effect biomarkers (measured as changes in system variables) in a balanced health situation reflects environmental stress that does not overtly challenge the system susceptibility

Fig. 3

Balance and stress in a biological system. Any biological system including human individuals may experience periods of balance (a1, b1 and c1) and periods of increased stress (a2, b2 and c2). Systems with different susceptibility have different risk of developing disease when exposed to the same stress. For a system with normal (moderate or low) susceptibility (a1), an increased stress may be tolerated (a2) making the system come closer to disease risk but without causing disease. For a system with high general susceptibility (b1) or specific susceptibility (c1), an increased environmental challenge may overstep the system tolerance leading to imbalance and heightened risk of disease (b2 and c2)

Fig. 4

Classification of dietary and health biomarkers within the space shaped by the three hyper-categories of biomarkers, exposure, susceptibility and effect. See text for further discussion of the proposed subclasses of biomarkers. The interpretation of the measurement of a biomarker depends on its intended use

Fig. 5

Proposed terms for initiating ontology for dietary and health biomarker

Fig. 6

System training by challenging. a In the naive, untrained but balanced state, the capacity to withstand a challenge is limited. b An increased challenge intensity will offset the system causing a temporary, weaker state. c Following a biological response such as enzyme induction, formation of antibodies or muscle re-building, the system becomes more resilient to challenge or stress