Joint Action “Nutrition & the Epigenome”
The second non-cofunded action in ERA-HDHL
In February 2018 the JPI HDHL launched a call for proposals focussed on the emerging field of nutrition and epigenetics. In total, 13 funding organisations from 11 countries participated in this call with a total budget of more than 8 M EUR.
The aim of this call is to support transnational, collaborative research projects that gain a better understanding of the diet-epigenome relationships and their effect on human health. This will allow the development and substantiation of intervention strategies for treating nutrition-related diseases and sustaining good health throughout the life course.
A total of 39 eligible full proposals were submitted to the JPI HDHL in April 2018. After peer review of the full-proposals, the Call Steering Committee selected 6 proposals, based on the ranking list provided by the scientific expert evaluation committee. The selected proposals requested a total of 6,8 M EUR of funding from the participating countries.
Starting in the first half of 2019 the six research consortia will work together in the upcoming three years towards a more complete understanding of the diet-epigenome relationships and their effect on human health.
Dietary Intervention in Food Allergy: Microbiome, Epigenetic and Metabolomic interactions
Cumulative evidence suggests that food allergy is associated with a multitude of environmental factors including hygiene habits, antibiotic use, lifestyle changes and in particular, diet. DIFAMEM aims to investigate the effects of food allergy treatment through intervention with a prebiotic dietary component, pectin, and using peach allergy as a model. This intervention should be safer than allergen immunotherapy. DIFAMEM will advance our understanding on how the interaction between dietary components and gut microbiota composition leads to epigenetic changes that provoke the immune modulation, and establish new strategies for dietary intervention in food allergy , with potential applications for other immune-related diseases.
The consortium consist of researchers from brings Spain, France and Germany. The consortium members have expertise in a wide variety of areas, including microbiome analysis, epigenetics, metabolomics, as well as clinical studies, immunology, and experimental animal models for food allergy.
Project coordinator: Dr. Maria Jose Torres.
DIFAMEM will (i) identify how different structural types of pectin affect regulatory immune responses, using mouse models, (ii) assess pectin effects on FA patients, and (iii) develop predictive probabilistic multivariate models for the treatment of FA via integrative analysis of epigenomic, microbiomic, metabolomics and immunologic profiles related to immune modulation. These profiles will be compared to those of patients treated with peach sublingual immunotherapy using samples stored at the IBIMA-Biobank.
Dietary induced methylome and transcriptome dynamics assessing nutrition impacts on cardiovascular and metabolic health
Cardiovascular and metabolic diseases are a primary cause of morbidity and mortality worldwide. Diet is a major risk factor for cardio-metabolic health, but is challenging to study in part because metabolic response to diet is highly individualised. Characterising the molecular pathways that mediate personalised responses to diet is critical to effectively tackle the current epidemic. Epigenetic mechanisms are key regulators of gene function that can change in response to external stimuli, including diet.
The DIMENSION consortium aims to deliver novel mechanistic insights into how exactly nutritional modifications can modulate the regulatory and functional genome to promote cardio-metabolic health. These insights will complement traditional population-based guidelines and inform the rapidly evolving area of individualised nutrition-based strategies.
The DIMENSION consortium brings together six partners from the UK, France, Germany, Spain, and the Netherlands with complementary research strengths and established track records in epigenetics, nutrition, cardio-metabolic health and disease, molecular biology, multi-omics, and epidemiology.
Project coordinator: Dr. Jordana Bell.
The work programme is based on (i) targeted postprandial and nutritional intervention studies to tackle the causal relationships between diet, epigenetic modifications and gene function, in combination with (ii) state-of-the-art analyses to characterize the links between diet, epigenetics, and cardio-metabolic health using novel diet measures including metabolomics in extensively studied cohorts, and (iii) functional follow-up experiments assessing the impact of diet-induced epigenetic and transcriptomic signals at the level of cells, within and across tissues.
Epigenetic effects of B-vitamins on brain health throughout life: scientific substantiation and translation of evidence for health-improvement strategies
The EpiBrain project aims to investigate the nutrition-epigenome-brain relationship across the lifespan, focusing. The EpiBrain project will lead to improved understanding of the role of B vitamins, their epigenetic effects and brain function in childhood and older age, with expected results anticipated to provide scientific substantiation to support nutritional strategies for sustaining better brain health through the lifespan
The consortium consists of four partners, two Canadian teams, one UK team, and one team in Spain. The synergy of the four consortium partners will bring together strengths in nutrition, epigenetics, dietetics, pediatrics, psychology and perinatal epidemiology.
Project coordinator: Dr. Yvonne Lamers.
EpiBrain aims to investigate diet-epigenome relationships and their associations with child brain function focusing on early exposure to maternal B-vitamins in utero and cognitive function in early stages of life. In light of the potential protective role of B-vitamins against cognitive decline in later life, the project will investigate whether the diet-epigenetic relationship affecting cognitive development is also related to cognitive function in later life.
Paternal RNA-mediated epigenetic inheritance of metabolic disorders: impact of weight loss on the human sperm epitranscriptome
Increasing evidence suggests that several non-communicable diseases, including obesity and its associated metabolic disorders, are inherited from parents to offspring over several generations by non-genetic mechanisms. HEROS aims to validate RNA-mediated epigenetic inheritance as a mechanism for obesity in humans. The major aim of the present study is to determine how the sperm epitranscriptome responds to environmental changes. Answering such a question might deliver valuable new insights into the molecular mechanism(s) involved in the process of the development of obesity and might also provide valuable new approaches to identify new obese-susceptibility.
The consortium brings together five teams (from France, Germany and Spain) with complementary expertise ranging from paternal epigenetic inheritance study, mouse experimental model, nucleotide RNA modification study, to clinical aspects of obesity diseases.
Project coordinator: Dr. Valerie Grandjean.
HEROS will collect sperm samples from two independently recruited cohorts of non-obese and obese men before and after weight-loss induced by surgery. They will (i) compare the epitranscriptome profiles of sperm from non-obese and obese men to identify RNAs that may be epigenetically (qualitatively or quantitatively) modulated by obesity; (ii) compare the epitranscriptome profiles of obese men before and post- surgery weight-loss to assess the potential reversibility of the newly acquired modifications and finally (iii) validate the role of human spermatozoa RNAs in epigenetic inheritance in an experimental in vivo mouse model.
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.
In the NutriPROGRAM consortium scientist from the Netherlands, UK, Canada, Germany and Spain will work together. The 3 key expertise of this consortium are nutritional expertise, epigenetics expertise and metabolic disease expertise.
Project coordinator: Dr. Janine Felix.
NutriPROGRAM will focus on an integrated set of maternal and infant nutrition-related exposures and the role of functional DNA methylation changes in associations with metabolic outcomes. NutriPROGRAM will make optimal use of these rich data and enrich these collaborations with new harmonised early-life nutritional factors and DNA methylation data.
Building on national cohorts and existing networks will enable NutriPROGRAM to develop a unique, important and long term sustainable network on early-life nutrition, epigenetics and long term metabolic outcomes.
A precision nutri-epigenetic approach to tackle the mother-to-child transmission of impaired glucose metabolism
The prevalence of co-morbidities associated with adult diabetes (T2D) continues rising.
Pounding evidence has established that the risk for impaired glycaemic health starts at conception and builds-up from one generation to another. PREcisE’s overarching goal studies life-course data from the pre-conceptual period up until adulthood to explore the life-course and molecular pathways pertaining the mother to offspring transmissibility of impaired glycaemic health. PREcisE will aim at breakthrough in understanding i) the causal epigenetic pathways underpinning fetal exposure to impaired glycaemic health, ii) the role played by the glycaemic and the inflammatory load of the diet in inducing and modulating DNA methylation and iii) the life-course consequences.
PREcisE consortium is multidisciplinary, uniting epigenetic researchers, nutrition scientists, clinical scientists, biostatisticians, bioinformaticians and epidemiologists from 5 countries (UK, France, Germany, Spain and the Netherlands).
Project coordinator: Prof. Marjo-Riitta Jarvelin.
PREcisE consortium will organise its working plan into three work packages to i) perform epigenome wide association study on glucose level exposure in utero followed by downstream analysis in a biobank of liver, skeletal muscles and adipose tissues, ii) infer the primary role of pre- and postnatal dietary exposures in modulating the association of methylation with adiposity and glycaemic health outcomes and iii) integrate its findings further into a life-course model for adiposity and glycaemic health outcomes trained in large birth cohort data.
JPI HDHL Joint Call Secretariat
Dr. Wilke van Ansem
ZonMw, the Netherlands