NutriPROGRAM: Early-life Nutritional Programming of Metabolic Health through Epigenetic Pathways

Pregnancy and infancy are critical periods for nutritional programming of metabolic health. Epigenetic changes seem to have a crucial role in pathways leading from early-life nutrition to metabolic health across the life course. NutriPROGRAM will study key maternal and infant nutrition-related exposures in relation to DNA methylation in mothers and offspring at different ages, and metabolic health across the life course. NutriPROGRAM will specifically focus on cause-and-effect relationships, reversibility of DNA methylation changes by nutrition, lifestyle, physical activity and microbiota, functional consequences of DNA methylation changes and translation into preventive or population-health strategies. Eventually, NutriPROGRAM will develop a sustainable, translational, international collaboration for studies on nutrition and epigenetics and their role in sustaining good health throughout the life course.

Pregnancy and infancy are critical periods for nutritional programming of metabolic health. Epigenetic changes seem to have a crucial role in pathways leading from early-life nutrition to metabolic health across the life course. NutriPROGRAM will study key maternal and infant nutrition-related exposures in relation to DNA methylation in mothers and offspring at different ages, and metabolic health outcomes across the life course. It will involve: (1) integrating sets of early-life nutritional factors in mothers and infants; (2) observational and intervention studies across the life course on metabolic outcomes including longitudinal growth and fat development, advanced imaging for body fat, metabolomic profiles and clinical outcomes; (3) cause-and-effect relationships of DNA methylation in the associations of nutrition-related factors and metabolic outcomes across the life course, by advanced causal inference approaches; (4) modification of DNA methylation changes by nutrition, lifestyle, physical activity and microbiota; (5) functional consequences of differences in DNA methylation using RNA expression and tissue specific approaches; and (6) translation into preventive or population-health strategies. NutriPROGRAM will capitalize on rich, existing and complementary nutritional, metabolic and epigenetic datasets from observational and intervention studies in pregnancy, childhood and adulthood, together covering the full life course. It will use knowledge and data infrastructures from different collaborative consortia including the Horizon2020 DynaHEALTH and LifeCycle Projects, the ERA-HDHL ALPHABET project, and the Pregnancy and Childhood Epigenetics (PACE) Consortium. Eventually, NutriPROGRAM will develop a sustainable, translational, international collaboration for current and future studies on nutrition and epigenetics and their role in sustaining good health throughout the lifecourse.

NutriPROGRAM will create a set of harmonised and integrated nutrition-related exposure indices that can serve as important novel and improved tools for scientists studying the relationships between nutrition and health both within and outside of NutriPROGRAM.

NutriPROGRAM will lead to the identification of novel DNA methylation loci with functional roles in the pathways underlying the relation of early-life nutrition and metabolic health, improving the knowledge base for future research and development activities.

NutriPROGRAM will lead to a better understanding of causality and modification of DNA methylation in the pathways leading from early-life nutrition to metabolic health. This will be a starting point for evidence-based preventive strategies and new nutrition-related interventions to reduce the worldwide health-related, economic and societal burden of obesity, dyslipidemia and type 2 diabetes in future generations.

NutriPROGRAM will develop a method for prioritisation of DNA methylation markers for functional follow-up that will be broadly applicable for the wider research community involved in DNA methylation research.

NutriPROGRAM will form a sustainable, translational international network on early-life nutrition, epigenetics and long term metabolic outcomes that will lay the foundation of further research in this area for many years to come.

Effective exploitation and dissemination of research results is an important aspect of the work performed in NutriPROGRAM and will be a focus of attention from the beginning of this project onwards. WP6 will be responsible for the management of dissemination and exploitation. Partners in the consortium will be encouraged to participate in active dissemination strategies, which will include:

- Publishing scientific articles: NutriPROGRAM will produce scientific manuscripts which will be submitted for publication in peer-reviewed journals.

- Presenting work at national and international scientific conferences: Consortium members will present the work performed in the consortium at relevant scientific conferences and will engage in discussions with fellow scientists and other interested conference participants.

- Training activities: Consortium partners will be actively involved in the training of early career researchers, transferring knowledge and skills to contribute to building a strong foundation for their research careers. In addition, all consortium partners are involved in teaching activities in their own and other institutions. These include lectures, seminars and workshops. Relevant results from the work performed in the consortium will be incorporated in these teaching activities.

- Communicating with the general public: NutriPROGRAM will disseminate scientifically credible findings, with appropriate interpretations and explanations, to the general public. Various ways of communication may be used, including traditional media, (institutional) websites and social media.

- Communicating with stakeholders: NutriPROGRAM will effectively translate relevant scientific findings to various stakeholders, including policy makers, healthcare professionals such as obstetricians, midwives, paediatricians and general practitioners, industry and patient organisations.