ERA-HDHL Cofund “Biomarkers for Nutrition and Health”

Early life programming of childhood health: a nutritional and epigenetic investigation of adiposity and bone, cardiometabolic, neurodevelopmental and respiratory health

WHAT: The ALPHABET project aims to improve our understanding of nutritional and epigenetic biomarkers of offspring health with a view to refining dietary exposure measures and to aid development of more effective evidence-based public health strategies with an emphasis on advocating a healthy diet in pre-pregnancy, pregnancy and early postnatal life, to reduce obesity, improve health and attenuate development of a range of adverse health outcomes in future generations.

WHO: The consortium includes 7 partners from 6 countries (Ireland, UK, France, The Netherlands, Poland and the US). The partners are Catherine Phillips, University College Dublin, Ireland; Caroline Relton, University of Bristol, UK; Nicholas Harvey, University of Southampton, UK; Barbara Heude, INSERM UMR 1153, France; Liesbeth Duijts, Erasmus MC, University Medical Center Rotterdam, Netherlands; Kinga Polanska, Nofer Institute of Occupational Medicine, Poland and James Hebert, University of South Carolina, US. The ALPHABET project is coordinated by Dr. Catherine Phillips in UCD.

HOW: Utilising biological samples and data from existing European longitudinal birth cohorts at the international forefront of lifecourse epidemiology we will investigate the complex relationships between maternal diet (defined by dietary quality and inflammatory potential), offspring health outcomes (including adiposity, bone, cardiometabolic, respiratory and neurodevelopmental health) and epigenetic patterns (DNA methylation) from birth throughout childhood.

Biomarkers for Infant Fat Mass Development and Nutrition

WHAT: Childhood obesity is a rapidly growing problem. Weight loss programs have limited effects and prevention is our only hope to stem this new epidemic. Infant fat mass development in particular, has long-term effects on later body fat mass and thus metabolic health. Lipid profiles may be used as biomarkers for fat mass development and provide predictive biomarkers for later childhood obesity.

WHO: BioFN brings together experts on Lipidomics (Dr Albert Koulman, University of Cambridge, UK); Paediatric endocrinology (Prof Anita Hokken-Koelega, Erasmus University, NL; Prof David Dunger and Dr Ken Ong, University of Cambridge, UK); Systems biology (Dr Henrik Bjørn Nielsen, Clinical Microbiomics, DK); Lipid metabolism (Dr Lars Hellgren Danish Technical University, DK). BioFN is coordinated by Albert Koulman.

HOW: BioFN will use lipid profiling in samples from two birth cohort studies, Sophia-Pluto (Rotterdam, NL) and Cambridge Baby Growth Study (UK) that both have very precise body composition data. This will allow us to develop predictive biomarkers for fat distribution. By quantifying the dietary effect on lipid metabolism, gut microbiome metabolism and fat distribution BioFN will provide tools to prevent of childhood obesity.

Gut Metabotypes as Biomarkers for Nutrition and Health

WHAT: Health reflects a balanced condition of all our eukaryontic cells and all the microbes living in and on our human body. In contrast, for many different disease entities it has been shown that the host-microbiome axis is dysregulated. Since the gut microbiome is known to be heavily influenced by diet, a balanced and symbiotic interplay between gut bacteria and the human organism might be a promising indicator for nutrition and health.

WHO: Our consortium combines two groups with access to large and well characterized human cohorts (Matthias Laudes, Kiel (Germany) and Jane Shearer, Calgary (Canada)) and two well established groups in Metabolomics experienced in liquid chromatography, mass spectrometry (LC-MS) and matrix assisted laser desorption ionization-time of flight (MALDI-TOF) based approaches (Karin Schwarz, Kiel (Germany) and Harald Koefeler, Graz (Austria)).

HOW: Identification of bacterial metabolites in the human serum as markers for nutrition and health using a three step program:

1. Identification of biopatterns of gut bacterial metabolites in the human serum;
2. Validation of the identified biopatterns in two independent international cohorts and in the same cohort at different time points;
3. Verification of the eligibility of the biopatterns as indicators for nutrition and health in two human intervention studies.
   
   

CirculAting Bile Acids as biomarkers of metabolic health - Linking microbiotA, Diet and Health

WHAT: Bile acids (BA) through TGR5 and FXR regulate mammalian inflammation, lipid, glucose, and energy metabolism, and are in turn regulated by diet: microbe interactions in the gut. CABALA_DIET&HEALTH aims to establish circulating BA profiles as biomarkers of health, modulated by diet which reflect a change in metabolic health.

WHO: Partner (Coordinator): Kieran Tuohy, Fondazione Edmund Mach, Italy. Partner: Gianfagna Francesco, Università degli Studi dell'Insubria, Italy. Partner: Susan Joyce, University College Cork, Ireland. Partner: Julie Lovegrove, University of Reading, UK. Collaborator: Iris Shai, Ben-Gurion University of the Negev, Israel.

HOW: Using existing data and new mechanistic studies we will provide direct evidence in humans that diet: gut microbiota interactions modulate plasma BA profiles and modulate host health. Our aim is to identify plasma BA profiles as health biomarkers and establish microbiota modulation of BA signalling as a unifying molecular basis for efficacious probiotic, prebiotic and polyphenol functional foods.

Development of Riboflavin biomarkers to relate dietary sources with status, gene-nutrient Interactions and Validated health Effects in adult cohorts

WHAT: Sub-optimal riboflavin status may be more widespread than is generally recognised across the developed world, because of the reliance on dietary data only in nutrition surveys, without biomarker evidence. DERIVE will address this gap by developing accessible riboflavin biomarkers for use in population surveys globally, and by demonstrating important functional, gene-nutrient and health effects of optimal riboflavin status in Canadian, Irish and UK cohorts.

WHO: This unique partnership of scientists from three jurisdictions brings together Canadian, Irish and UK population cohorts to study novel nutrient factors, and related gene-nutrient interactions, and functional effects that influence health, including hypertension, a leading cause of mortality. Our proposal will lead to enhancements in health and disease prevention that can be marketed as a global strategy rather than one that is population specific. The partners are Mary Ward, Ulster University, Ireland (Coordinator); Yvonne Lamers, University of British Columbia, Canada; Albert Flynn, University College Cork, Ireland and Peter Weber, DSM Nutritional Products, Switzerland.

HOW: The proposed study will access bio-banked blood samples (collected under the JINGO initiative http://www.ucd.ie/jingo/) and data from one the most comprehensive dietary surveys in the EU, the Irish National Adult Nutrition Survey (www.iuna.net) as well as bio-banked specimen and data from the BC Generations Project (www.bcgenerationsproject.ca), part of the Canadian Partnership for Tomorrow Project, a major research platform for the study of disease causation.

Fatty Acid Metabolism – Interlinking Diet with Cardiometabolic Health

WHAT: FAME aims to a) identify novel lipidomics biomarkers as biomarkers of fatty acid status and of future cardiometabolic clinical events, b) establish relationships between whole diets and specific foods with tissue status of fatty acids as explanatory factors for diet relationships with cardiometabolic health, and c) to investigate genetic determinants of fatty acid status and metabolism which modify the physiological effects of dietary intake.

WHO: Prof. Matthias Schulze, German Institute of Human Nutrition, Germany(coordinator) Prof. José López-Miranda, University of Cordoba, Spain Prof. Miguel Ángel Martínez González, University of Navarra, Spain Prof. Julie Lovegrove, University of Reading, UK Prof. Anne Marie Minihane, University of East Anglia, UK

HOW: Lipid metabolites as novel biomarkers will be identified in prospective studies on type 2 diabetes. Potential for dietary modification will be tested in controlled trials. Specific FAs and novel lipid metabolites will be tested as biomarkers of dairy fat intake and as markers of cardiometabolic health. Polyphenols and candidate genes as determinants of response to FA intake will be evaluated in the trials and cohorts.

TAGging dietary Fiber intake and their interest for health by measuring biomarkers related to the gut microbiota

WHAT: The FiberTAG project will establish a set of biomarkers linking dietary fiber (DF) intake and gut-microbiota related health effect. We aim at refining the concept of DF based on novel biological effects that can occur upon gut microbiota-nutrients interaction by using existing cohorts and by developing innovative approaches to evaluate the health interest of novel insoluble DF.

WHO: The FiberTAG consortium gathers 4 academic principal investigators from Belgium, France, Germany and Canada, respectively. They gather complementary research expertises such as

1. host physiology with emphasis on management of cardio-metabolic disorders;
2. intervention studies based on diet and prebiotic DF;
3. microbial ecology;
4. data integration and modelling.

The partners are Nathalie Delzenne, Université catholique de Louvain, Belgium (Coordinator); Martine Laville, CRNH-RA, France; Jens Walter, University of Alberta, Canada and Stephan C. Bischoff, University of Hohenheim, Germany. Two industrial partners (Kitozyme, Véronique Maquet, Belgium and Mondelez, Sophie Vinoy, France) will develop and provide selected insoluble fiber for the intervention studies. 

HOW: Specific metabolites selected as biomarkers of microbiota-driven fermentation and gut-related functions will be analyzed in 5 existing cohorts of healthy or overweight populations in which the fecal microbiota composition and DF intake have been (or will be) analyzed. New intervention studies will be performed in healthy and cardiometabolic risk volunteers to evaluate the interest for health of two insoluble fibers (chitin-glucan and a wheat bran fraction).

Metabolic HEALTH through nutrition, microbiota and tryptophan bioMARKers

WHAT: HEALTHMARK will investigate the complex associations between the gut microbiota, tryptophan availability and bioactive microbial metabolites of tryptophan, and diet and metabolic health. Phenotypes of obesity with low visceral adipose tissue as well as metabolically healthy obese phenotypes will be used to characterize metabolic health. The gut microbiome will be looked at as a potential reservoir of health-related biomarkers, both in terms of composition and function (microbial metabolites) open to modulation by diet.

WHO: HEALTHMARK is an interdisciplinary and transnational project. The project comprises five partners from four EU countries with complementary expertise and exemplars of scientific excellence in this research area. These partners are Ute Nöthlings, University of Bonn, Germany (Coordinator); Monique M.B. Breteler, German Center for Neurodegenerative Diseases, Germany; John F Cryan, the APC Microbiome Institute at University College Cork/ Teagasc, Moorepark Food Research Centre, Ireland; Fulvio Mattivi, Fondazione Edmund Mach, Italy and Lucile Capuron, Institut National de la Recherche Agronomique, France.

HOW: HEALTHMARK will identify, replicate and validate biomarkers in.existing human population studies - the DONALD, the Rhineland, the Obesity, and the MUCOL Study - which have dietary information, information on body composition, and biological samples. Gut microbiota composition will be assessed by 16S ribosomal RNA sequencing. The project will use targeted and untargeted metabolomic approaches to determine levels of relevant precursors, metabolites and bioactives in blood and urine samples.

Oxylipins signature to monitor the cardiometabolic status and its response to dietary intervention

WHAT: There is an urgent need to find reliable early biomarkers of the cardiometabolic syndrome (CardMetS) allowing intervention before irreversible damage develops while assessing the efficacy of nutritional prevention. Targeted lipidomic profiling of oxylipins could provide relevant candidate biomarkers. Our main objective is to uncover and validate the oxylipin signatures reflecting the trajectory from health to CardMetS and its relationships with diet.

WHO: The OXYGENATE project gathers complementary and multidisciplinary expertise in:

1. Nutrition:

• Dr C Gladine, INRA, France
• Dr A Astrup & L H Larsen, UCPH, Denmark

1. Analytical chemistry/lipidomics:

• Dr N Schebb, Univ. Wuppertal, Germany
• Dr J Newman, UC Davis, USA

1. Nutritional epidemiology and cardiometabolic health:

• Dr M Touvier, INSERM, France
• Dr A Szuba, Univ. Wroclaw, Poland 

HOW: Using an optimized targeted lipidomic approach and leveraging 2 independent prospective cohorts (i.e. the Polish PURE and the French NutriNet-Santé cohorts) and 2 whole-diet interventions (Shopus and iMAPS) we will identify and validate oxylipin signatures (i) differentiating individuals at different stages of CardMetS and with different dietary patterns and (ii) evolving consistently with dietary interventions affecting the cardiometabolic endpoints.

SALivAry bioMarkers of mediterraneAN Diet associated with long-tERm protection against type 2 diabetes mellitus

WHAT: Saliva offers the advantages of simple and non-invasive sampling and is a rich source of biomarkers thanks to the high diversity of its microbiome, proteome and metabolome. Saliva composition is also dependent on diet. The SALAMANDER project aims at identifying and validating salivary signatures indicative of healthy dietary choices (adherence to a Mediterranean diet) with a positive long-term health outcome (protection against T2DM).

WHO: SALAMANDER brings together partners from France, the United Kingdom and Spain: Institut National de la Recherche Agronomique (Martine Morzel, coordinator, the Centre for Taste and Feeding Behaviour), Université de Bordeaux (Catherine Féart, Bordeaux Population Health), King’s College London (Gordon Proctor, Dental Institute) and Universidad Autónoma de Madrid (Fernando Rodríguez-Artalejo, Cardiovascular and Nutritional Epidemiology group).

HOW: Using the UKBiobank resource, subjects will be categorized based on their health status (T2DM) and diet. The saliva microbiome, proteome and metabolome of selected subjects will be analyzed, and analytical data integrated to define a multimarker signature of a healthy Mediterranean diet associated with protection against T2DM. The validation phase will also include elderly subjects of the ENRICA and 3City-Bordeaux cohorts, to verify whether such signatures are conserved with ageing.

Innovative Technological Approaches for validation of Salivary AGEs as novel biomarkers in evaluation of risk factors in diet-related diseases

WHAT: Recent findings convincingly demonstrate that Advanced Glycation End Products (AGEs) are modifiable by diet and reflect changes in healthy state. SALIVAGES will investigate whether that diet-induced AGEs can act as reliable biomarkers of changes in health status and/or risk, focusing on the most highly accessible source of AGEs, the saliva.

WHO: The project is proposed by a highly qualified multidisciplinary research team with complementary experience in different fields of biochemistry, pathology, pharmacology and analytical chemistry. The scientific network involves five different European countries: ITALY (Massimo Collino, University of Turin), SPAIN (Rosa M. Sainz, University of Oviedo), IRELAND (Lokesh Joshi, National University of Ireland Galway), ROMANIA (Ilea Aranka, University of Cluj-Napoca), GERMANY (Thomas Henle, Technische Universität Dresden).

HOW: SALIVAGES will provide innovative and original tools for assessing status and efficacy of interventions, namely biosensors, metabolomics and biomimic approaches. It will also deepen our understanding of the early events leading to the changes in health status, by multidisciplinary approaches based on the integration of preclinical biological and molecular studies, analytical and food chemistry, information technologies, and glycomic analyses.

Valerolactones and healthy Ageing: LInking Dietary factors, nutrient biomarkers, metabolic status and inflammation with cognition in older adults.

WHAT: Polyphenols, particularly procyanidins (abundant in foods such as tea, cocoa, grapes, nuts and berries), may be beneficial in maintaining better cognitive function in ageing, but investigating their role in relation to health is hampered by the lack of robust biomarkers of dietary intake. We will validate novel plasma biomarkers of procyanidin-rich foods and link them with inflammation, metabolic health and cognition in an ageing European population.

WHO: VALID brings together partners from the UK, Ireland and Italy with interdisciplinary expertise in nutrition, food bioactives, immunology, geography and clinical gerontology, with the aim of conducting impactful research linking dietary polyphenols with cognitive health in older adults. VALID builds on the Joint Irish Nutrigenomics Organisation (JINGO) project and specifically its component Trinity, Ulster, Department of Agriculture (TUDA) cohort study. The partners are Helene McNulty, Northern Ireland Centre for Food and Health, UK (Coordinator); Daniele Del Rio, University of Parma, Italy and Anne Molloy, Trinity College Dublin, Ireland.

HOW: VALID draws on the TUDA cohort, a unique resource on 5200 adults aged 60-102 years recruited from the UK and Ireland, providing a range of biomarkers and health measures. Apart from performing new analysis on bio-banked TUDA samples, we will access ‘TUDA 5+’, a follow-up study of 1000 participants from the original cohort 5 years after initial investigation, to determine the role of procyanidin-rich foods in preventing cognitive decline over a 5-year follow-up period.