Tessa M.G. Dronkers1, Guido Hooiveld1, Anouk Gijbels1, Rinke Stienstra1 Stine M. Ulven2, Lydia A. Afman1
1 Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands; 2 Department of Nutrition, University of Oslo, Oslo, Norway tessa.dronkers@wur.nl
Background: Fasting measurements are routinely used in clinical nutrition studies to standardise baseline conditions and serve as a basis for evaluating intervention effects and postprandial responses, implicitly assuming that these measurements are reproducible within individuals. Peripheral blood mononuclear cell (PBMC) transcriptomics is increasingly used to investigate immune-metabolic responses to nutritional interventions, yet the extent to which fasting PBMC gene expression varies within individuals over time remains poorly understood.
Methods: Fasting PBMC whole-transcriptome array and RNA sequencing datasets from multiple nutritional intervention studies will be analysed to quantify intra-individual variability in gene expression across repeated fasting measurements. Variability will be assessed at both the gene and pathway level using repeated-measures statistical models, complemented by transcriptomic deconvolution to estimate PBMC composition.
Results: Analyses are currently underway. Preliminary results will describe the magnitude of intra-individual variation in fasting PBMC gene expression across studies, and the contribution of estimated PBMC composition to observed variability. We will also identify genes and pathways that demonstrate relatively stable or highly variable expression within individuals.
Conclusion: This study will evaluate a fundamental assumption underlying clinical nutrition research – that fasting measurements provide a stable biological baseline. This knowledge will strengthen the interpretation of longitudinal fasting PBMC whole genome transcriptome analyses, and support the identification of true nutritional intervention effects.