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Application of new technologies and methods in nutrition research-the example of phenotypic flexibility. (NUtriTech)

NutriTech will build on the foundations of traditional human nutrition research using cutting-edge analytical technologies and methods to comprehensively evaluate the diet-health relationship and critically assess their usefulness for the future of nutrition research and human well-being. Technologies include genomics, transcriptomics, proteomics, metabolomics, laser scanning cytometry, NMR based lipoprotein profiling and advanced imaging by MRI/MRS.
All methods will be applied in an integrated manner to quantify the effect of diet on "phenotypic flexibility", based on metabolic flexibility (the capacity for the organism to adapt fuel oxidation to fuel availability). However, NutriTech will move beyond the state-of-the-art by applying these integrated methods to assess the underlying and related cell biological and genetic mechanisms and multiple physiological processes of adaptation when homeostasis is challenged. Methods will in the first instance be evaluated within a human intervention study, and the resulting optimal methods will be validated in a number of existing cohorts against established endpoints.
NutriTech will disseminate the harmonised and integrated technologies on a global scale by a large academic network including 6 non-EU partners and by providing an integrated and standardised data storage and evaluation platform. The impact of NutriTech will be multifold and exploitation is crucial as major breakthroughs from our technology and research are expected. This will be achieved by collaboration with a consortium of 8 major food industries and by exploitation of specific technologies by our 6 SME partners. Overall, NutriTech will lay the foundations for successful integration of emerging technologies intro nutrition research.

Universidad de Córdoba

The overall objective of NutriTech is to develop novel standardised methods for global use, using stateof-the-art and beyond state-of-the-art technologies, for studying the effects of diet and life-style on human health. To be able to achieve this, the large pan-European consortium is extended with several non-European partners from different continents, to ensure global acceptance of the methods developed here. Only by achieving worldwide harmonisation of the methodologies used in nutrition research, can
developments in this field be significantly improved as it will allow the direct comparison of results, thus enabling real collaboration and exchange in the worldwide nutrition research community.
NutriTech will work towards this objective by studying the phenotypic flexibility of humans, when challenged with foods and/or food components. This topic was chosen as the most relevant methods and technologies available and under development (see Table 1 above) can be validated within this area of research. Several sub-objectives of NutriTech are therefore to:
1. Evaluate the value of emerging technologies in the quantification of subtle effects of dietary interventions on health;
2. Evaluate the added value of emerging technologies to elucidate mechanisms of action in human studies;
3. Validate the use of emerging technologies for studying human metabolic and physiological adaptive processes in response to a shift from a suboptimal to a healthy diet;
4. Develop the integrated quantification of aspects of phenotypic flexibility as biomarkers of diet-related health improvement;
5. Develop methods integrating established as well as emerging technologies to study nutritional effects on health;
6. Provide guidelines and protocols to harmonise the use of the developed integrated methods;
7. Establish a data infrastructure in a global network of laboratories to disseminate and implement the new methods and technologies developed in nutrition research;
8. Valorise the new integrated technology for the food industry in a renewed effort to demonstrate health benefits of defined dietary interventions.

1. Store and share all project data via the nutritional phenotype database.
2. Analyse and evaluate the study results beyond the single methods level
3. Embed NutriTech results within relevant publicly available data
4. Derive practical and integrated methods from the extensive phenotyping technologies for use in cohort studies
5. To apply the "practical phenotype" package" and specific components of the "extensive phenotype" packages to established suitable observational longitudinal and cross-sectional cohorts with available biobanks and data-rich databases including sophisticated bioimaging techniques.
6. To validate the "food intake" biomarkers in established observational (EPIC) and intervention (CORDIOPREV) cohorts with rich and repeated nutritional information
7. To validate the "the "practical phenotype" package" and specific components of the "extensive phenotype" as markers of optimal health (i.e. absence of onset of metabolic diseases) in cohorts of different ages, socioeconomic status and behavioural and dietary habits and test its application to large populations.
8. To validate whether the "practical phenotype" package" can detect beneficial changes induced by dietary/behavioural interventions in large clinical studies and differences in response resulting from genetic variability.
9. Create a sustainable global network to promote, disseminate and harmonise emerging technologies in state-of-the-art nutrition and health research.
10. Disseminate the project's approach and results to academic, governmental and industry stakeholders, focussing on Europe with additional global.

Food metabolome Database
Panel of biomarkers for quantification of macronutrient intake and food sources
Options for development of a kit based system for measurement of the panel of biomarkers.
Algorithms for integration of the panel of biomarkers and classical dietary
intake data
New tools in food intake assessment
Use of nutritypes in food intake quantification
Study protocol
Ethical committee approval
SOPs for all study parts
Execution of the human study
All data relevant to the human study execution available in the nutritional phenotype database
Biosample reference materials and SOP´s for challenges tests
PBMC hormone sensitivity assay methods
Tracer flux analysis assay method
NMR based lipoprotein profiles from intervention study
Metabolome profiles from intervention study
Protein profiling from challenges in the human intervention study
Nutritional status and diet-related results
Lipidomics from samples before and after intervention
Clinical (bio) chemistry and biochemical results
SOP for challenge studies
Best practice methods for cohort studies on 'optimal health parameters'
Panel of biomarkers for a kit-based system.
Scientific manuscript on "phenotypic flexibility" concept
MR images, spectra of liver and pancreatic fat content of all subjects
computer-based model for blood-based alternatives for imaging technologies
Fat content and distribution of all subjects
Compilation of relationship between different fat depots and basic biomarkers
SOPs for MRI technology transfer to other centres
Novel algorithm for MRI techniques to assess fat distribution
SOP for transcriptomics and proteomics of adipose tissue and skeletal muscle
SOP for accumulation and oxidation of 14C-labeled substrates
SOP for immunofluorescence of certain proteins
SOP for the use of PBMCs isolation for transcriptome analysis
Evaluate the use of the PBMCs transcriptome as biomarker for diet-related health
PBMCs metabolome analysis of the intervention in dbNP
Dataset of transcriptomics and proteomics in adipose tissue and skeletal muscle in dbNP
Improved assays for description of phenotypic flexibility
Dataset of metabolomics of ligand assay in dbNP
Dataset of accumulation and oxidation of 14C -labelled substrates
Immunofluorescence of proteins in human biopsies/cells
Dataset in dbNP of metabolomics of ligand assay
Publication on the PBMCs transcriptome analysis
Method on PBMCs transcriptome as marker of diet-related health
Integration of biopsy data with data from other WPs to assess muscle and adipose phenotypic flexibly
Improved cost effective assays for description of phenotypic flexibility in muscle and adipose tissue
Abstracts/papers on research findings in phenotypic flexibility in muscle and adipose tissue
Modules for nutrigenomics in dbNP
LSC protocol for Genome Integrity Maintenance phenotype
GIMP measurements in lymphocytes and buccal cells
Analysis of GIMP measurements of the life style intervention study subjects
Analysis of whole genome exon sequence of the life style intervention study subjects
Analysis of copy nr variation of the life style intervention study subjects
Relevant Standard operating methods in Methods Portal
Input on genetic variation parameters to the "practical phenotypic flexibility methods'
Analysis of genomics variation results in the life style intervention study
dbNP version for NutriTech for all beneficiaries
Integrated analysis plan of NutriTech study data
Results of the integrated data analysis
SOP(s) for a (series of) practical phenotypic flexibility method(s) to quantify henotypic flexibility
Integrated analysis of Phenotypic Flexibility
Ethical approvals for cohort work
Analysis plan for the validation of the practical phenotypic flexibility methods in the "NutriTech c
Validated panel of biomarkers for macronutrient intake
Validated phenotypic flexibility biomarker panel for acute changes in lipid and glucose metabolism
Validated phenotypic flexibility biomarker panel to detect health/disease status in large cohorts
Validated phenotypic flexibility biomarker panel to detect changes
Phenotypic flexibility biomarkers to detect genetically driven differences
Target Groups Contact Details Database, first version
First publishable communication
Dissemination workshop report
Second publishable communication
Regional harmonisation and dissemination workshop in New Zealand/Australia
Regional harmonisation and dissemination workshop in Canada/USA
SME brokerage event
All new methods inserted in the NuGO methods portal
Dissemination workshop 2 report
Final publishable communication
Concise monograph
Target Groups Contact Details
Database (TGCD) final catalogue
Food Industry Consortium meetings
Advisory board
Ethics Committee
Gender action committee
Knowledge management committee

NutriTech explores the integration of emerging technologies in nutrition research by performing a concerted technology and research project and by collecting and integrating information and results from already performed studies using emerging technologies in nutrition research. The results are globally disseminated by providing a harmonized nutrition research study toolkit that not only presents integrated technology application methodology, but also an integrated data storage, distribution and evaluation platform.
1. Expected impacts listed in the work programme
1.1 Contribution to the expected impacts
Description of impacts
We distinguish five kinds of impact: a) Call-specific impacts, b) Impact on R&D in nutrition research, c) Social impact; d) Economic impact, e) Impact on technical standards/ guidelines. These different kinds of impact are separately discussed below.
1.1.a Call specific impacts
The aim of topic KBBE.2011.2.2-02 is to explore and understand the power and limitations of novel technologies in nutrition research and their use in combination with the more traditional methodologies in order to make the results/studies comparable and/or interconnected. Expected impacts will be:
a Understanding of the potential and limitations of the latest techniques in nutrition research.
b Scientific and technological breakthroughs in the development of integrated tools and methods for nutrition research.
c Contributing to a harmonisation of methodologies worldwide.

As described below, NutriTech will achieve these three major impacts.

Ad a) NutriTech will significantly improve our understanding of the power and limitations of novel technologies in nutrition research. Specifically, NutriTech will improve our understanding of the applicability of a wide range of emerging tools and technologies (whole genome genetics and epigenetics, transcriptomics, targeted proteomics, metabolomics and lipidomics, magnetic resonance imaging, NMR-based lipoprotein profiling, and laser scanning cytometry) for detecting diet-induced subtle physiological changes at the gene, cell, organ and organismic level. Moreover, NutriTech will explore the use of metabolomics based quantification of food intake.

Ad b) NutriTech will achieve scientific and technological breakthroughs in the development of integrated tools and methods for nutrition research. All knowledge on the applicability of stand-alone techniques and tools for nutrition research that will become available in the NutriTech project will add value to the state of the art "toolkit" for nutrition research. By understanding the applicability of integrated "established" and "emerging" technologies, NutriTech will provide nutrition researchers with the opportunity to optimally combine the application of established techniques and analytical / mechanistic studies with the new technologies and methods in nutrition research. Thus, both established and emerging technologies will be integrated into new methods and various methods to study different
aspects of the same physiological process. NutriTech will provide proof of concept that this integrated approach will provide a powerful tool to achieve scientific breakthroughs in nutrition research.

By application of the "new and old" technologies and methods to phenotypic flexibility as a core aspect of health, i.e. the maintenance of the ability to adapt to continuously changing dietary and environmental challenges, we will achieve a scientific breakthrough in nutrition research. This will include developing a series of biomarker processes involved in maintaining optimal health. Because these processes represent multiple aspects of complex physiological processes, optimal use of our methods and tools will also best be achieved in an integrated manner. Thus NutriTech will provide integrated technology and
bioinformatics to describe and quantify integrated biological processes.

Ad c) NutriTech will contribute to harmonisation of methodologies worldwide. New technologies are rapidly and continuously emerging and offer new methods to quantify aspects on human physiology and phenotype, and are thus potentially useful in nutrition research. Although it is up to the individual researchers to explore innovations in their research, a number of these technologies now need benchmarking in order to come to a harmonized and comparable use, adopting them in the core of nutrition research. Tools and techniques for nutrition research will be evaluated by a large pan-European consortium extended with research laboratories from Canada, USA, Australia and New Zealand. This
worldwide consortium will collaborate on the harmonization of a wide range of (combined old and) new techniques and methodologies for nutrition research. Only by achieving worldwide harmonisation of the methodologies used in nutrition research, developments in this field can be significantly improved as it will allow the direct comparison of results, thus enabling real collaboration and exchange in the worldwide nutrition research community.
Emerging technologies introduce the additional challenge of dealing with enormous amounts of data.
NutriTech will implement and disseminate a public domain data infrastructure for nutrition research that allows the capturing, storage and analysis of data, respecting local ownership and allowing seamless sharing based on worldwide accepted standards.
The NutriTech partners have committed themselves to promote the harmonized implementation of new technologies and methods. This will be achieved by applying the global network of the NutriTech partners.
Finally, NutriTech will liaise with a consortium of a number of the world leading food industries in further exploring and exploiting the use of the developed methods concerning diet-related health claims.
We foresee that the aspects of the call-specific impact listed above will become visible in (scientific) articles, through websites (e.g. NuGO website), in stakeholder meetings and most importantly, in adoption of the integrated tools and technologies in new nutritional studies in academic, industrial and regulatory setting.

1.1.b Impact on R&D in nutrition research
The results of NutriTech are expected to speed up nutrition research for the coming decades by delivering harmonized and beyond state-of-the-art tools and technologies for nutrition research.
Moreover, the integrated "old" and "new" technologies will add tools for analytical / mechanistic studies to the currently state-of-the-art studies in nutrition research. As a result of this, not only the research organizations participating in the present project will be able to speed up their research and achieve major breakthroughs, also worldwide research organizations beyond the consortium and industrial companies will implement these methodologies in their research. Major scientific breakthroughs are expected on the relation between specific nutrients and health and disease.
One example of a scientific breakthrough with the new and harmonized research methodologies will be provided in the NutriTech project. Summarized, in the present project, NutriTech will achieve a scientific breakthrough in nutrition research by developing a series of biomarkers at all levels (gene, cell, organ and organism) that quantify processes involved in maintaining diet-related optimal health (phenotypic flexibility). This knowledge will be further developed towards future application in health practice
Moreover, the availability of biomarkers for phenotypic flexibility will lead to a wide variety of additional research on the diet and health relationship, including the development of healthy diets and dietary components and diet / lifestyle combinations.

Strategy to bring about the expected impact
The harmonized methodologies can directly be implemented in the participating research laboratories.
Proper dissemination beyond the consortium (see chapter 3.2) will ensure the worldwide application of the knowledge, tools and methods generated in NutriTech.

1.1.c. Economic impact
a) The economics impact of a healthy diet is tremendous, given the relationship between a healthy diet with healthy ageing and the adverse effects of unhealthy diets (obesity and related pathologies, cancer, and more). European food industry has a track record of innovation and competitive advantage as compared to e.g. the American competitors. Yet, partly due to the current enforcement of the EFSA (European Food Safety Authority) procedures on health claim substantiation, a tendency to withdraw from this innovation is observed. This tendency needs to be counteracted for the sake of the (European) consumer, who should optimally profit from progress in research. NutriTech therefore focuses on the exploration and exploitation of emerging technologies specifically in the area of quantification of health related processes. We believe that by integrating validated and harmonized techniques and tools, starting with those resulting from the NutriTech project, it will become possible to substantiate health claims of food nutrients. Since the market for such products is enormous, the availability of such tools will certainly stimulate the European food industry to target this market and. It is evident that this will boost the European food industry.

Strategy to bring about the expected impact
The tight collaboration of the NutriTech consortium with a consortium of European Food Industries will ensure that the validated and harmonized technologies will directly be applied by the European Food Industry in health claim substantiation research.
b) The NutriTech project is expected to result in several exploitable products. Effective exploitation of these results will be ensured by the participation of six SMEs. These SMEs will be in an excellent position to exploit the results generated in the NutriTech project once the IP rights have been protected

1.1.d Impact on technical standards/ guidelines
NutriTech will obtain a thorough understanding of the power and limitations of emerging and state-of-theart technologies and tools for nutrition research. On basis of this knowledge, standards for the application of these technologies for nutrition research will be developed. The harmonized technologies will directly be implemented in the second phase of the NutriTech proposal.
Thus, in the application of these new technologies, we will establish new methods that can be applied in nutrition and health research. We will design and disseminate Standard Operation Procedures and test these in nutritional cohorts. We will also provide to the nutrition research community the bioinformatics infrastructure that captures, integrates, shares and evaluates the high density data and results of all studies that apply these methods.

Strategy to bring about the expected impact
The NutriTech partners have committed themselves to promote the harmonized implementation of new technologies and methods. This is achieved by a global network, where the prominent partners in various regions (Europe: the NuGO consortium and NutriTech partners; USA: Tufts University; Canada: Universities of Toronto and Alberta; Australia: CSIRO; New Zealand: University of Auckland). A large number of research projects and consortia, longitudinal and prospective cohorts are connected to NutriTech.

1.1.e Social impact
This proposal focuses on ‘phenotypic flexibility', as a major determinant of the diversity in response to life style interventions and therefore as an important aspect in prevention strategies for the combat of obesity and type 2 diabetes. Improved insights in the various aspects of ‘phenotypic (in)flexibility', could offer a significant contribution to the urgent need for additional preventive strategies against these diseases. The increasing prevalence of obesity and type 2 diabetes is a major health care problem worldwide. The need for these additional preventive strategies is emerging since more than 50% of the adult population in Europe is overweight, and 10% to 40% is considered clinically obese. The global figure of diabetes prevalence is expected to rise by 40% between 2000 and 2030, increasing absolute numbers to 366 million people. The rapidly escalating number of patients poses a tremendous burden on the public health system. Therefore a substantial reinforcement of research activities is urgently warranted to prevent a socio-economic disaster. Global cooperation between scientists from different
disciplines is in this an important pre-requirement for success.
As described above, NutriTech will significantly improve our understanding of the relation between the effects of diet and nutrition on health and disease, using the example of phenotypic flexibility, which is easily expandable to other areas in the diet&health relationship. Furthermore, the extensive phenotyping approach opens avenues for assessing this relationship the level of the individual. On the longer term, this will lead to methods to assess the health status of an individual and to improve health by giving
personalized advice with respect to diet or food supplements.

Steps to bring about these impacts
Through the NutriTech project, harmonized and validated technologies to study the health effects of diet and dietary ingredients will become available. We believe that by applying these technologies, an increasing number of food claims can be substantiated and as a result thereof, will be granted by EFSA.
The availability of tools to substantiate health claims will result in novel food products with a health claim. Such products will improve health, predominantly by preventing diseases. This will not only improve quality of life but also reduce public health care costs.


Dpto. Medicina

Code PAIDI: CTS-525

José López Miranda. partner. 

Universidad de Córdoba

Budget of Andalusian group: € 120000

7 Medical University Of Varna MUV Bulgaria
11 Vereniging European Nutrigenomics Organisation NUGO A Netherlands
15 VITAS AS Vitas Norway
16 BIQUALYS BV Biqualys Netherlands
24 Nestlé Institute of Health Sciences NIHS Switzerland

Keywords: Nutrition, diet, genomics
Duration: 48 months. January, 1th 2012 to December, 31th 2015
Project cost: € 6,981,187.20 €