Universitat Rovira i Virgili

TRAJECTÒRIA DEL GRUP INVESTIGADOR

(english description)

The Human Nutrition Unit (HNU) is an interdisciplinary and dynamic team with extensive experience and sufficient autonomy in developing epidemiological studies, clinical trials, and basic research. The scope of this research group is to evaluate the effect of dietary patterns or dietary compounds on obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), cardiovascular diseases (CVD), colorectal cancer and male fertility. We focus on the effect of dietary components and functional foods on energy balance, lipid profile, inflammation, oxidation and glucose metabolism, as well as on the effect of dietary patterns on the primary prevention of CVD and diabetes.

The HNU also works with collaborators of recognized prestige from other Universities, both Spanish and internationally. This demonstrates the competence, and commitment of the Unit with the internationalization of Spanish research, and highlights the capabilities of the group in terms of leadership as well as communication and relationships with external organizations. The incorporation of expert researchers in different disciplines (medical doctors, dietitians, biologists, biotechnologists, food technologists, and psychologists), has provided the group with several skills related not only with the development and implementation of large clinical trials and cohort studies, but also with the capability of obtaining quantitative data; knowledge of data analysis techniques (including, among others, survival analysis, epigenetics, metabolomics and metagenomics); ability to network and create contacts; creative ability, originality and innovation, and the ability to improvise and find ways to overcome any difficulties. Moreover, the group stands out for its capacity to obtain funding (public and private) and for its extensive scientific production.

In performing its work, the HNU has research facilities at the Rovira i Virgili University, equipment in place, and the link with the Nutrition Unit and the Obesity Unit of the Sant Joan de Reus University Hospital that enables our team to integrate research into applied clinical care. Of note, the Obesity Unit has been recognized by the European Association for the Study of Obesity (EASO). The HNU is recognized since 2009 as a consolidated group at regional level (AGAUR - 2017SGR 691), and since 2010 at National level (CIBERobn - Instituto de Salud Carlos III).
Over the last number of years, the group had led two large clinical trials for the primary prevention of cardiovascular disease (PREDIMED and PREDIMED-Plus) along with several other clinical trials (EPIRDEM, FERTINUTS) and observational studies (CORALS and LEDFERTIL).
 
The PREDIMED study, http://www.predimed.es (lifestyle intervention trial with a Mediterranean diet in the context of primary prevention of CVD) is a large multi-center parallel clinical trial conducted in 7,447 participants at high CVD risk that has started in 2003 and finished in 2009 and has been successfully conducted in order to prevent CVD, T2D and other related outcomes. In this trial, our group has particularly focused on the study of inflammation, kidney function, T2D and its complications, and metabolic syndrome (MetS). PREDIMED has changed the current dietary recommendations for CVD and T2D worldwide, including the Dietary Guidelines for Americans. With the availability of a huge database, the HNU  has several hypotheses related to its research interests that will continue to be explored in the future. Currently, with the biological samples obtained from this study, several analyses have been conducted on different OMIC´s platforms (e.g., transcriptomics, genomics, metabolomics). These projects have been conducted in collaboration with the PREDIMED consortium and several other research groups, funded by the Spanish Ministry of Health; Fundació Marató TV3 (294/C/2015; Fundación Ramon Areces  and US National Institutes of Health (NIH). As we are actively following this cohort, in the next 5-y, we will also test the long-term efficacy of the interventions on several other important outcomes (such as different types of cancer, Alzheimer's disease, and other degenerative diseases).

With the completion of PREDIMED, on 2014, the HNU has begun another multi-center RCT, PREDIMED-Plus (https://www.predimedplus.com), to study the effects of a 6-y lifestyle modification program for weight loss. The PREDIMED-Plus clinical trial has become the biggest milestone in nutrition investigation accomplished in Spain, investigating the effect of an energy-restricted MedDiet and physical activity on: 1) CVD incidence and mortality; weight loss; 2) incidence of other related chronic diseases; 3) changes in CVD risk factors and other intermediate outcomes. Vast amounts of data and biological samples (plasma, serum, DNA, urine, stools) are being collected as part of the PREDIMED-Plus, in order to be utilized for further studies. The recruitment of this study (n= 6,874) was finished in 2016. As coordinator of this study involving 23 research groups recruiting participants, and 6 lab centres, the group has received an array of National, European and USA grants. With all of these projects and collaborations, we have also developed skills in the area of precision medicine using different approaches such as OMICs, which we are now applying in epidemiologic and clinical studies.

Another important target of the Unit related to PREDIMED and PREDIMED-Plus, is to work on the predictability of T2D, chronic kidney disease (CKD), and CVD using metabolome profiling and genetic polymorphisms. The intense collaboration with other international groups of research facilitates the validation of our findings in other international cohorts (the Health Professionals Follow-up Study, Nurse's Health Study, MESA and EPIC studies). During the last 5 years we have identified several metabolites, genetic polymorphisms and pathways implicated in the risk of CVD, diabetes, heart failure, atrial fibrillation, and peripheral artery disease. We also tested the mediating effect of the interventions on CVD, diabetes, heart failure or atrial fibrillation risk on genetic and plasma metabolome variations. In the last two to three years we also have assessed the effect of our interventions and diabetes status on impulsivity, compulsivity, cognition and the mediating effect of the gut microbiota on these end-points. For this purpose, we have had two National grants (one from the ISCII) and 3 European grants as Co-investigators (Eat2BeNice; https://eat2benice.eu, STOP; http://www.stopchildobesity.eu; and PRIME; https://prime-study.eu).

Our team, within the framework of the PREDIMED study, leads also an ambitious project (LIKIDI study) on diet and CKD, assessing also the relationship and/or the potential mediating effect of inflammatory and oxidative stress markers and a broad spectrum of metabolites as a novel approach in CKD pathogenesis.

Our group has participated in different NIH-funded projects in collaboration with Navarra University, Harvard University, Broad Institute, and other groups belonging to the PREDIMED study. Prof. Salas-Salvadó is co-PI of the projects R01DK102896 (Dietary Interventions, Metabolites, and Risk of Type 2 Diabetes; 2014-2018) and R01DK112940 (Circulating plasma metabolites, diet, and risk of type 2 diabetes; 2018-2021), and co-investigator of the project R01HL118264 (Mediterranean diet, Metabolites, and cardiovascular Disease; 2013-2021). Currently, a new T2D-project is being evaluated for funding.

Research on those projects have explored the association between certain metabolites related with important pathways such as glycolysis/gluconeogenesis, tricarboxylic acid cycle, lysine, arginine, tryptophan, glutamate, branched chain/aromatic amino acids, choline, acylcarnitines, ceramides, lipidomic profile, and T2D and/or CVD. Moreover, the consortium has also published manuscripts unraveling metabolites associated with the whole Mediterranean diet and with certain key food groups belonging to the Mediterranean diet, such as red wine, coffee, protein, walnuts, and dairy products. All these manuscripts have been published in international and prestigious journals.

CORALS (http://www.corals.es), is a multicentric, long-term (10 year follow-up) large (n=2200) observational prospective pediatric cohort study that allows us to explore in the future the association between the lifestyle and other determinants on adiposity, cognition and CVD risk factors. This observational ongoing study has started two years ago and we are collecting a large amount of information and biological samples (plasma, serum, buffy coat, urine and stools).

Another subject of interest of the group is male infertility, an important public health problem in the last few decades. In particularly, we have been interested in the effect of obesity, food and food patterns on semen quality. FERTINUTS was an international randomized clinical trial conducted by our group in order to assess the effects of chronic nut consumption on semen quality and functionality in a cohort of healthy males, and described several potential mechanisms. Recently, we have started a cross-sectional cohort study (LEDFERTIL) to explore potential lifestyle and environmental determinants of male fertility that we plan to expand to other investigators´ groups of other countries (e.g., USA, Poland, Spain, and Italy).  

Our group was also very interested analyzing the beneficial effects of fat-rich food on several outcomes. Using epidemiological approaches and clinical trials, we explored the effect of the consumption of nuts on several intermediate outcomes using our developed and acquired methodological techniques in collaboration with national and international (India and USA) research groups.

Prof. Jordi Salas-Salvadó is the Coordinator of the PREDIMED-Plus study, member of the steering committee of PREDIMED, and the director of the URV Chair in nuts. He has extensive experience in studying the relationship between food, food components or dietary food patterns in obesity and other cardiovascular risk factors. As a medical doctor, he has been both a successful leader and collaborator in several large nutritional and pharmacological trials for the management of obesity. His research in the last years has also focused on the modulation of circulating metabolome, microbiome and several epigenetic tags including microRNAs and its potential role in obesity. Dr. N Babio, member of the staff, is dietitian-nutritionist and has participated in most of the clinical trials that have been conducted in our unit. Dr. Babio now leads the CORALS and LEDFERTIL studies. Dr. N Becerra-Tomás, is a nutritionist who is specialized in epidemiology with classical statistical epidemiology skills and is an expert of systematic reviews and meta-analyses. Dr. A Díaz-López is epidemiologist, specialized in diabetes, renal function and kidney diseases. Dr. Francisco García-Gavilan is epidemiologist specialized in nutritional epidemiology and metabolomics, and is the PREDIMED-Plus project manager. Dr. S Nishi is a postdoctoral researcher from Canada, she is a dietitian and expert in conducting clinical trials and meta-analysis. Dr. Ma Angeles Martinez Rodriguez is a researcher with a large background in molecular biology and specialized on endocrine disruptors and metagenomics. She is responsible for our laboratory and is skilled in all the molecular analysis techniques required (i.e. metagenomics, telomere analysis). Dr. Santiago Ríos Azuara is a pharmacist, with a master degree in Biochemistry, Molecular Biology and Biomedicine and specialized on bioinformatics. 

Cumulatively, the Human Nutrition Unit is well versed in conducting robust scientific research given the team background in basic sciences and expertise in clinical research. This guarantees the translationally of the current proposal.