title: The exposome concept in a human nutrigenomics study: evaluating the impact of exposure to a complex mixture of phytochemicals using transcriptomics signatures.
abstract: The application of transcriptome analyses in molecular epidemiology studies has become a promising tool in order to evaluate the impact of environmental exposures. These analyses have a great value in establishing the exposome, the totality of human exposures, both by identifying the chemical nature of the exposures and the induced molecular responses. Transcriptomic signatures can be regarded as biomarker of exposure as well as markers of effect which reflect the interaction between individual genetic background and exposure levels. However, the biological interpretation of modulated gene expression profiles is a challenging task and translating affected molecular pathways into risk assessment, for instance in terms of cancer promoting or disease preventing responses, is a far from standardised process. Here, we describe the in-depth analyses of the gene expression responses in a human dietary intervention in which the interaction between genotype and exposure to a blueberry-apple juice containing a complex mixture of phytochemicals is investigated. We also describe how data on differences in genetic background combined with different effect markers can provide a better understanding of gene-environment interactions. Pathway analyses of differentially expressed genes in combination with gene were used to identify complex but strong changes in several biological processes like immune response, cell adhesion, lipid metabolism and apoptosis. These observed changes may lead to upgraded growth control, induced immunity, reduced platelet aggregation and activation, diminished production of reactive oxidative species by platelets, blood glucose homeostasis, regulation of blood lipid levels and increased apoptosis. Our findings demonstrate that applying transcriptomics to well-controlled human dietary intervention studies can provide insight into mechanistic pathways involved in disease prevention by dietary factors.
authors.affiliation: Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands s.vanbreda@maastrichtuniversity.nl.
authors.forename: Simone G J
authors.initials: SG
authors.lastname: van Breda
authors.affiliation: Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Lonneke C
authors.initials: LC
authors.lastname: Wilms
authors.affiliation: Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Stan
authors.initials: S
authors.lastname: Gaj
authors.affiliation: Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Danyel G J
authors.initials: DG
authors.lastname: Jennen
authors.affiliation: Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Briedé
authors.affiliation: Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Jos C S
authors.initials: JC
authors.lastname: Kleinjans
authors.affiliation: Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
authors.forename: Theo M C M
authors.initials: TM
authors.lastname: de Kok
mesh_terms: D030541:Databases, Genetic; D004032:Diet; D004781:Environmental Exposure; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks; D006801:Humans; D008954:Models, Biological; D054647:Nutrigenomics / Q000379:methods; D064209:Phytochemicals / Q000494:pharmacology*; D012107:Research Design; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome
chemical_list: D064209:Phytochemicals