Identification of effect and exposure biomarkers in human dietary intervention studies : Using various omics approaches

Nutrition can play a pivotal role in preventing and sometimes even reversing obesity and associated diseases. Traditionally, the effects of nutrition on health were assessed by the use of a few single biomarkers, known as classical biomarkers of a disease state. While the low hanging fruits of diet-induced effects on health have been identified using these markers, new approaches are needed to assess the more subtle diet-induced effects of nutrition on health. Hence, there is a need for more sensitive and comprehensive diet effect biomarkers. Developments in the omics field have paved the way to explore and identify these new biomarkers. Additionally, these omics techniques are being used to improve measurements of dietary intake, by providing objective measurements for short and long term dietary intake, called exposure biomarkers. In this thesis, we identified both diet effect and exposure biomarkers, by performing several human intervention studies with varying dietary exposures and study designs, and by using various omics approaches.In these human intervention studies combined, we found that metabolomics is a powerful tool to identify diet effect biomarkers, next to its effective use to identify exposure biomarkers. In addition, we observed that compliance with a dietary intervention, as reflected by an increase in exposure biomarkers, does not always translate into a response in diet effect biomarkers. Furthermore, despite clear significant effects at the intervention group level, we observed large inter-individual differences in response in the diet effect biomarkers. These inter-individual differences might eventually provide leads for personalised dietary advice in the future. This thesis also confirmed the ambiguity that exists among the different biomarker categories, and highlighted the relevance to explore whether a biomarker is an exposure, effect, or health biomarker, or can reflect multiple conditions. We also showed that although many potential exposure biomarkers have been identified in the literature, well-validated exposure biomarkers are missing, and thereby hamper their current use in nutrition research. Lastly, we showed that microRNA expression in the subcutaneous adipose tissue can be affected by diet and weight-loss. However, before microRNAs can provide a useful addition to the omics arsenal within nutrition research, several challenges need to be overcome, such as the current limited knowledge on the interaction between microRNA, genome, and health. If these challenges can be overcome, the future of microRNA analysis within nutrition research holds strong promise.&nbsp