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Location:

The 3^rd Scientific Workshop of POSITIVe will be hosted by Porto Palace Hotel Thessaloniki.

Adress: 65, 26th Octovriou Str., Thessaloníki, 546 28.

Local Organizers:

• Antonia Kaltsatou (University of Thessaly, Greece)
• Christos Kontogiorgis (Democritus University of Thrace, Greece)
• Eirini Deligiannidou (Democritus University of Thrace, Greece)

Scientific Committee

• Banu Bayram (University of Health Sciences, Istanbul, Turkey)
• Mar Garcia-Aloy (University of Barcelona, Spain)
• Antonio González-Sarrías (CEBAS-CSIC, Spain)
• Rocío García-Villalba (CEBAS-CSIC, Spain)
• Geoffrey Istas (King’s College London, United Kingdom)
• Pedro Mena (University of Parma, Italy)
• Laurent-Emmanuel Monfoulet (INRA, France)
• Noemi Tejera (University of East Anglia, United Kingdom)
• Mireia Urpi-Sarda (University of Barcelona, Spain)

14:00 - 14:10

Welcome & Introduction

Metabolomics Session

Chairs: Claudine Manach (INRA, France) - Rocio García-Villalba (CEBAS-CSIC, Spain)

14:10 - 14:50

The Translation of Lipid Profiles to Nutritional Biomarkers in the Study of Infant Metabolism

Albert Koulman (NIHR BRC Nutritional Biomarker Laboratory; NIHR BRC Core Metabolomics and Lipidomics Laboratory; University of Cambridge; UK)

In the first months of life the diet of every infant will consists entirely out of milk, which will be either human breast milk, formula, or both. Many studies have shown that growth, development and disease risk in later life are different between infants starting their life on breast milk or formula. We developed a lipidomics approach that allows us to study lipid metabolism of infants using minimally invasive heel prick samples. With this approach we have been able to show that the lipid metabolism of breast-fed infants is significantly different to those who receive only formula and that some of these differences are associated with growth rates. We have validated key features of the lipid profile as nutritional biomarkers and we are currently trying to understand what part of the milk composition is responsible for these effects and how.

14:50 - 15:20

Biomarkers of food intake and effect after consumption of plant-based dietary patterns in cardiovascular risk participants

Mireia Urpi-Sarda (Barcelona University, Spain)

The consumption of plant-based foods and the adherence to healthy dietary patterns are associated with lower risk of chronic diseases. Their robust measurement is an essential component in studies attempting to establish links between intake or adherence and health outcomes. Currently, they are measured in nutritional epidemiology by the use of questionnaires such as the dietary scores or dietary recalls. We applied metabolomic approaches to study biomarkers of Mediterranean diet adherence and polyphenol-rich food intake. Additionally, these approaches also allowed identifying metabolomic biomarkers of effect of these patterns which could explain altered pathways or metabolic routes involved. The results will provide a better understanding of health benefits of these dietary patterns in nutritional epidemiology.

15:20 - 15:50

Host: microbiome co-metabolic processing of dietary polyphenols – a cross-over study with different doses of apple polyphenols in healthy subjects

Marynka Ulaszewska (Istituto Agrario San Michele all'Adige, Italy)

Human metabolism of apple polyphenols is a co-metabolic process between human encoded activities and those of our resident microbiota. We are delighted to show nutrikinetics study where the aim was to effectively identify the metabolic products of various classes of apple polyphenols using an untargeted metabolomics. We assessed whether particular profiles of apple derived plasma/urine metabolites could be related to individual members of the gut microbiota. Finally we evaluated whether an higher concentration of polyphenols in the apple matrix, would lead to a corresponding increased metabolic output.

15:50 - 16:10

Flash Poster Presentation

Nutri-genetics, -genomics, and -epigenomics Session (I)

Chairs: Wil Van der Berg (University of Antwerp, Belgium) - Antonio González-Sarrías (CEBAS-CSIC, Spain)

16:40 - 17:20

The impact of genotype on the metabolism and bio-efficacy of plant polyphenols

Anne Marie Minihane (Head of Nutrigenetics and Director of Research and Innovation, Norwich Medical School, University of East Anglia (UEA), Norwich, UK)

At a population level, there is growing evidence of the beneficial effects of plant polyphenols on health. However, there is wide variability in the response to increased intake, which is likely due to heterogeneity in their absorption, distribution, metabolism and elimination (ADME). A number of factors, including age, sex, gut microflora and genotype influence these metabolic process. In this presentation the impact of common gene variants on polyphenol ADME and bio-efficacy will be considered, which may help establish and refine dietary polyphenol intake recommendation for different population subgroups.

17:20 - 17:50

Implications of predictive Genomics for drug response and food intake

George Patrinos (University of Patras, Greece)

Precision medicine aims to interrelate one’s genetic profile with disease predisposition and response to the most commonly used drugs. Nutrigenomics is gradually becoming an important aspect of precision medicine that, contrary to pharmacogenomics that predict drug efficacy and/or toxicity, examines the bidirectional interactions of the genome and nutritional exposures, and attendant health and disease outcomes. However, at present, despite the knowledge gained from nutrigenomics research, integration into the daily clinical practice requires an evidence-based approach to validate that personalized recommendations result in health benefits to individuals and do not cause harm. As (Camp and Trujillo (2014). Stated “…whether or not the knowledge gained from nutrigenomics can be integrated into the everyday lives of consumers is yet unknown”. Here, we will contextualize our recent study of 38 genes included in commercially available nutrigenomics tests and make a call in the best interest of the nutrigenomics science community, governments, global society, and commercial nutrigenomics test providers that new evidence evaluation and synthesis platforms are created concerning nutrigenomics tests before they become commercially available. The proposed assessment and synthesis of nutrigenomics data should be carried out on an ongoing dynamic basis with periodic intervals and/or when there is a specific demand for evidence synthesis, and importantly, in ways that are transparent where conflict of interests are disclosed fully by the involved parties, be they scientists, industry, governments, citizens, social scientists, or ethicists.

17:50 - 18:20

Gene expression profiling in whole blood cells from healthy men after chronic blueberry consumption

Geoffrey Istas (King’s College London, UK)

Blueberries are associated with cardiovascular health benefits and are therefore interesting candidates for disease prevention. The aim of this work was to investigate the underlying molecular mechanism of action by evaluating their impact on both gene and miRNA expression in peripheral blood mononuclear cell (PBMC) using integrated nutrigenomic analysis. In a parallel double-blinded randomized controlled trial, young healthy males consumed a blueberry drink over a one-month period. Whole gene and miRNA profiling was investigated using Agilent human microarrays. In vitro monocyte to endothelial adhesion assays were performed using primary endothelial cells (human umbilical vein endothelial cells (HUVECs)) and monocyte cell line THP-1 after incubation with plasma-derived phenolic acids.

Microarray and statistical analyses revealed significant changes in the expression of 608 genes in PBMCs. Bioinformatic analysis showed enrichment of cellular processes involved in the regulation of inflammation, immune response, leukocyte chemotaxis, cell adhesion, cytoskeleton remodelling or in phase-two metabolism. Nutrigenomic analysis also revealed changes in the expression of 3 miRNAs (hsa-miR-126-5p, hsa-miR-181c-3p, hsa-miR-30c-5p). A reduced expression after blueberry consumption was observed for miRNA's 126-5p and 181c-3p, which have both been described as mediators of cardiovascular diseases. Bioinformatic analyses allowed us to identify potential target genes and these miRNA and pathway analyses showed that they are also involved in the regulation of cell inflammation, transmigration of chemotaxis. The in-vitro study revealed a significant reduction (62 ± 10 %) of adhesion of monocytes to an endothelial monolayer after incubation with blueberry derived phenolic acid metabolites. Integration of these nutrigenomic studies suggests that anthocyanins from blueberry can lower monocyte adhesion to endothelial cells, an initial step in the development of atherosclerosis. The findings contribute to a better understanding on how berry-derived (poly)phenols might prevent cardiovascular diseases..

Nutri-genetics, -genomics, and -epigenomics Session (II)

Chairs: Baukje De Roos (Rowett Institute - United Kingdom) - Geoffrey Istas (King’s College London, United Kingdom)

9:00 - 9:40 

Understanding the mechanisms underlying the effects of the PATHWAY-27 bioactive enriched foods 

Clarissa Gerhäuser (Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany)

The aim of the PATHWAY-27 project (www.pathway27.eu) is to investigate the role and mechanisms of action of three bioactives (docosahexaenoic acid, β-glucan, anthocyanins) as bioactive-enriched foods (BEF) using three widely-consumed food matrices (dairy-, bakery-, egg products) on risk factors of the metabolic syndrome (MetS). Functional analyses address bioactive effects on adipocytes and liver cells in vitro and on subcutaneous fat tissue in vivo when administered to humans as ingredient of the BEFs, and integrate various advanced omics techniques (transcriptomics, metabolomics, epigenomics microbiomics). After an introduction of the overall project effects of bioactives on epigenetic mechanisms including DNA methylation and posttranscriptional histone modifications will be presented.

9:40 - 10:10

A genetic basis for the inter-individual LDL cholesterol response to plant sterol consumption: from an association to an ongoing validation trial

Dylan Mackay (University of Manitoba, Canada)

Plant sterols share a similar chemical structure to cholesterol but are found in plants. Consumption of plant sterols in doses of 1-3 grams per day has been repeatedly shown to lower total and LDL cholesterol. However, data from trials involving plant sterol consumption demonstrate considerable inter-individual variations. Endogenous cholesterol synthesis has been associated with the variability in response to plant sterol consumption and this has subsequently been associated with genetic variations. Some of these genetic associations have been replicated in human clinical trials and a clinical trial involving prospective recruitment of participants with specifics genosets is now ongoing to validate these associations.

10:10 -10:40

Systems biology characterization of immunomodulatory properties of Echinacea in monocyte cells

Ken Declerck (University of Antwerp, Belgium)

Different Echinacea preparations are used world-wide to stimulate the immune system, and for preventing and treating common cold. Especially the use of Echinacea purpurea (purple coneflower) species is popular in Western countries. Different Echinacea purpurea extracts or compounds derived from Echinacea showed antioxidant, antibacterial, antifungal, antiviral and mosquitocidal activities in cell culture experiments. However, studies in human intervention studies showed less significant effects, probably due to high inter-individual variation in response to Echinacea extracts. By a systems biology approach, we identified significant modulation of immunomodulatory interferon responses and the involvement of MAPK kinases, upon integration of transcriptomic, epigenomic and kinomic activity profiles.

Microbiomics Session

Chairs: Mireia Urpi-Sarda (University of Barcelona, Spain) - Laurent-Em. Monfoulet (INRA, France)

11:00- 11:40

Gut microbiota functions: metabolism of nutrients and other food components

Kieran Tuohy (Fondazione Edmund Mach, Italy)

The human intestinal tract is colonised by a diverse collection of microorganisms, the gut microbiota, which differ in both species composition and metabolic potential spatially and temporally along the gut. This microbiota is shaped by host genetics and environmental factors (e.g. drugs, antibiotics) and most importantly, by the foods we eat. Conversely, the gut microbiota plays an important role in metabolising complex food components, changing their chemical structure, bioavailability and biological activity. Microbial fermentative and hydrolytic activities break down complex polyphenols into smaller phenolic acids which may then by absorbed by the host. These small phenolic acids are now thought to account for many of the health effects attributed to plant polyphenols in fruit and vegetables for example. The gut microbiota converts complex polysaccharides including fibers and prebiotics, which would otherwise escape digestion in the intestinal tract, into short chain fatty acids (SCFA). SCFA are involved in many important physiological activities including pathogen exclusion, intestinal permeability and mucosal energy metabolism, education and regulation of the immune system, glucose and lipid metabolism in the liver and the metabolic and immune output of adipose tissue. More recently, microbial involvement in human amino acid metabolism has been suggested, and it appears to be involved in regulation of important amino acid derivatives like serotonin and gamma-aminobutyric acids, molecules involved in human immune, metabolic and brain function. Conversely, the gut microbiota has also been implicated in production of metabolites linked to host systemic disease, especially trimethylamine N-oxide. The enterohepatic circulation of bile acids is in large part driven by complex diet:microbe interactions, which determine the quantities of bile acids persisting to the distal ileum and colon, bile acid deconjugation and subsequent production of secondary and tertiary bile acids. These products of microbial bile acid metabolism are potent regulators of host immune and metabolic function. Indeed, binding of bile acids by fibers and complex polyphenols in the small intestine followed by increased exposure to lactobacilli and bifidobacteria in the distal small intestine may be involved in the apparent health effects of both healthy dietary patterns rich in fiber and polyphenols (e.g. the Mediterranean style diet) and also how functional foods mediate the mechanism of action. The complex nature of diet:microbe interactions in the gut and how they may be manipulated to impact on human health are the subject of a recently funded JPI ERA project, CABALA_Diet&Health. Using examples from existing and ongoing studies, this presentation will discuss how these diet:microbe interactions contribute to the functioning of both the gastrointestinal track and health promoting diets and foods. It will also discuss methodological approaches to study these complex interactions taking into account both the temporal and spatial nature of nutrient/food metabolism in the gut.

11:40 -12:10

Diet-responsive gut anaerobes as drivers of inter-individual variation in response to consumption of plant food bioactives

Alan Walker (University of Aberdeen, UK)

The human gut microbiota is hugely complex, but we are beginning to understand which constituent bacterial species can respond to consumption of particular dietary substrates. Furthermore, it is now clear that inter-individual variation in microbiota composition can result in very different responses to consumption of identical diets, and that this variation may have important subsequent impacts on host health. In my talk I will cover recent work identifying various diet-responsive microbes, and provide examples of the roles that they play in release of bioactives such as ferulic acid from plant structures. I will conclude by discussing why we may ultimately need to consider the role of underlying microbiota composition/activities in personalised nutrition-based strategies.

12:10 - 12:40

Individuality in the gut microbiota determines rutin metabolism

David Berry (University of Vienna, Austria)

The human intestine is home to a diverse community of microorganisms collectively called the gut microbiota. The gut microbiota performs important services for its host such as the metabolism of polyphenolic compounds that influence their systemic availability and therefore their beneficial properties. In this talk, I will discuss how individual variation in the gut microbiota can impact the metabolism of polyphenols using the example of microbial rutin degradation. I will also discuss novel approaches in gut microbiota research that facilitate an enhanced understanding of gut microbiota function and the activity of key members of the microbiota.