Advances in Understanding the Molecular Basis of the Mediterranean Diet Effect

Posted with permission from the Annual Review of Food Science and Technology, Volume 9 by Annual Reviews, http://www.annualreviews.org.Increasingly, studies showing the protective effects of the Mediterranean diet (MedDiet) on different diseases (cardiovascular, diabetes, some cancers, and even total mortality and aging indicators) are being published. The scientific evidence level for each outcome is variable, and new studies are needed to better understand the molecular mechanisms whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases but also discussing other related diseases. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a critical review of the limitations of the studies undertaken and propose new analyses and greater bioinformatic integration to better understand the most important molecular mechanisms whereby the MedDiet as a whole, or its main food components, may exercise their protective effects

Technological Applications for the Automation of Food Questionnaires in Medical Studies: a state-of-art-review and future prospective

Applications for automating the most commonly used dietary surveys in nutritional research, Food Frequency Questionnaires (FFQs) and 24 h Dietary Recalls (24HDRs), are reviewed in this paper. A comprehensive search of electronic databases was carried out and findings were classified by a group of experts in nutrition and computer science into: (i) Computerized Questionnaires and Web-based Questionnaires; (ii) FFQs and 24HDRs and combinations of both; and (iii) interviewer-administered or self-administered questionnaires. A discussion on the classification made and the works reported is included. Finally, works that apply innovative technologies are outlined and the future trends for automating questionnaires in nutrition are identified

Metabolites, genomics, epigenomics, exposomics and health: Focus on serum bilirubin concentrations in subjects with metabolic syndrome from a Mediterranean population

Pòster presentat al congrés "Understanding Human Diseases Through Metabolomics: Interactions Among the Genome, Proteome, Gut Microbiome and Nutrition", Metabolomics and Human Health, Gordon Research Conference (February 3 - 8, 2019 Ventura, CA, United States)Although metabolomics aims at the measurement of small molecules (metabolites) in a biological sample, this knowledge requires additional information on the related genetic variants, epigenetic regulators and environmental factors (diet, smoking, physical activity, etc.) in order to translate the knowledge into actionable therapeutic or preventive evidence for complex disease outcomes. We focused on serum bilirubin, a metabolite generated when heme oxygenase catalyzes the degradation of heme (Figure 1). This produces biliverdin, which is converted into bilirubin by biliverdinreductase. Bilirubin is further processed in hepatocytes, where unconjugated bilirubin is conjugated by uridine diphosphate-glucuronosyltransferase (UDP-GT) to a water-soluble form for excretion. For decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice. However, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases

Nutrigenetics, nutrigenomics and Mediterranean diet: a new vision for gastronomy

Tanto la nutrigenética como la nutrigenómica son disciplinas dentro de la denominada genómica nutricional, que, en sentido amplio, proporciona el marco de integración de las distintas ómicas con las ciencias de la alimentación y nutrición. Tras décadas de estudios nutrigenéticos y nutrigenómicos, se dispone de una cantidad relevante de conocimientos para plantear su aplicación en la denominada nutrición de precisión. Esta nueva disciplina plantea que hay que tener en cuenta las características particulares de la persona para proporcionar la mejor dieta para prevenir o tratar la enfermedad. Los marcadores ómicos se consideran relevantes en dicha personalización. Existen muchos alimentos, nutrientes y patrones de dieta que se han investigado en nutrigenética y nutrigenómica; entre ellos, podemos mencionar el patrón de dieta mediterránea. A pesar de la heterogeneidad en la definición de dieta mediterránea, existen varios estudios que muestran que la dieta mediterránea puede interaccionar con el genoma, disminuyendo el riesgo de enfermedad en las personas genéticamente más susceptibles. Paralelamente, algunos estudios están mostrando los mecanismos por los que la dieta mediterránea puede ejercer este efecto protector. Conocer con más detalle la susceptibilidad genética, los mecanismos epigenéticos, la influencia del metaboloma y de otras ómicas puede ser relevante en gastronomía, entendida como la práctica del arte de elegir, cocinar y comer los alimentos. Esta influencia ómica no solo podemos encontrarla en los fenotipos de salud-enfermedad, sino también en la percepción del sabor y del olor de los alimentos (las preferencias por determinadas comidas). Todo ello, bien integrado, puede contribuir al incremento del disfrute a la vez que se sigue una alimentación saludable.Both nutrigenetics and nutrigenomics are disciplines that form part of what is known as Nutritional Genomics, which, in the widest sense, provides the framework for integrating different omics with food and nutrition sciences. After decades of nutrigenetic and nutrigenomic studies, there is a large enough amount of knowledge to consider its application in so-called precision nutrition. This new discipline seeks to take into account the particular characteristics of the individual in order to provide the best diet for preventing or treating a disease. Omic markers are considered to be of importance to that personalization. There are many foods, nutrients and dietary patterns that have been researched in nutrigenetics and nutrigenomics, including the Mediterranean Diet pattern. Despite heterogeneity in defining the Mediterranean Diet, there are various studies that show that the Mediterranean Diet can interact with the genome, so reducing the risk of disease in the most genetically susceptible individuals. Likewise, several studies have recently been revealing the mechanisms through which the Mediterranean Diet may exercise this protective effect. Understanding genetic susceptibility, epigenetic mechanisms, the influence of the metabolome and other omics in more detail may be important in gastronomy, understood as the practice of selecting, cooking and eating food. This omic influence can not only be found in health-disease phenotypes, but also in food taste and smell perception and preferences for certain dishes. Considering all of these together may contribute to an increase in enjoying and at the same time pursuing healthy eating

Crosstalk between smoking and the genome in older subjects with metabolic syndrome through genomics, epigenomics and transcriptomics

Pòster presentat a EMBO - EMBL Symposia Multiomics to Mechanisms - Challenges in Data Integration. September (11th – 13th 2019 European Molecular Biology Laboratory. Heidelberg, Germany)Tobacco smoking (Figure 1) is a major cause of cardiovascular diseases (CVD), and appears to have a multiplicative interaction with the other major CVD risk factors (lipids, hypertension, diabetes and others present in the metabolic syndrome (MetS). Several omics have analyzed the separate effects of tobacco smoking on the genome, epigenome, transcriptome, metabolome, etc. However an integrated omics approach can help to better understand the crosstalk between tobacco smoking and the genome

Untargeted metabolomics based on ultra-high-performance liquid chromatography-ion mobility-quadrupole time-of-flight mass spectrometry for biomarker discovery of orange intake in a cross-over trial

Pòster presentat al congrés "Understanding Human Diseases Through Metabolomics: Interactions Among the Genome, Proteome, Gut Microbiome and Nutrition", Metabolomics and Human Health, Gordon Research Conference (February 3 - 8, 2019 Ventura, CA, United States)Diet is one of the most important lifestyle factors associated with health status. Currently, one of the main limitations of nutritional epidemiology and nutritional genomics is the difficulty in the measurements of dietary intake. In observational studies carried out in a large number of participants, the most commonly applied tools for estimating dietary intake are based on self-reporting, including food frequency questionnaires (FFQ) for the assessment of regular consumption (usually 1-year), or 24-h recalls for 1-day assessment. However, such instruments for data collection may contain several recall bias and other systematic or random errors that may have a great effect in the subsequent associations found. Although in recent years, it has been an improvement in increasing the validity and precision of food questionnaires due to the use of the new information technologies (Figure 1), these instruments are still biased and additional information based on objective biomarkers of food intake is needed

Ultra-Performance Liquid Chromatography-Ion Mobility Separation-Quadruple Time-of-Flight MS (UHPLC-IMS-QTOF MS) Metabolomics for Short-Term Biomarker Discovery of Orange Intake: A Randomized, Controlled Crossover Study

A major problem with dietary assessments is their subjective nature. Untargeted metabolomics and new technologies can shed light on this issue and provide a more complete picture of dietary intake by measuring the profile of metabolites in biological samples. Oranges are one of the most consumed fruits in the world, and therefore one of the most studied for their properties. The aim of this work was the application of untargeted metabolomics approach with the novel combination of ion mobility separation coupled to high resolution mass spectrometry (IMS-HRMS) and study the advantages that this technique can bring to the area of dietary biomarker discovery, with the specific case of biomarkers associated with orange consumption (Citrus reticulata) in plasma samples taken during an acute intervention study (consisting of a randomized, controlled crossover trial in healthy individuals). A total of six markers of acute orange consumption, including betonicines and conjugated flavonoids, were identified with the experimental data and previous literature, demonstrating the advantages of ion mobility in the identification of dietary biomarkers and the benefits that an additional structural descriptor, as the collision cross section value (CCS), can provide in this area

The Gln241His polymorphism in the carbohydrate response element binding protein (MLXIPL) gene

Comunicació presentada com a pòster a European Association of Human Genetics Conference, May 23-26, 2009, Vien

Influence of the adherence to the Mediterranean diet on the effect of smoking on genomewide methylation among subjects with metabolic syndrome

Pòster presentat al congrés " Epigenetics: Playing with the Gameof Life" celebrat al University Hospital Halle (Saale) entre els dies 13-15 de 2019.Tobacco smoking is an important risk factor for lung cancer, respiratory diseases and cardiovascular diseases, among others. Moreover, smoking can speed up the normal aging process of several tissues increasing the biological age. Changes in methylation due to smoking have been demonstrated at several loci across the genome, particularly in long-term smokers (Figure 1). The most consistent association reported in different populations has been decreased methylation in smokers in comparison with non-smokers at the CpG cg05575921, located in the gene for the aryl hydrocarbon receptor repressor (AHRR) located in chromosome 5

MicroRNAs and Drinking: Association between the Pre-miR-27a rs895819 Polymorphism and Alcohol Consumption in a Mediterranean Population

Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consumption at the population level. Our aim was to investigate the association between a functional polymorphism in the pre-miR-27a (rs895819 A>G) gene and alcohol consumption in an elderly population. We undertook a cross-sectional study of PREvencion con DIeta MEDiterranea (PREDIMED)-Valencia participants (n = 1007, including men and women aged 67 +/- 7 years) and measured their alcohol consumption (total and alcoholic beverages) through a validated questionnaire. We found a strong association between the pre-miR-27a polymorphism and total alcohol intake, this being higher in GG subjects (5.2 +/- 0.4 in AA, 5.9 +/- 0.5 in AG and 9.1 +/- 1.8 g/day in GG; p(adjusted) = 0.019). We also found a statistically-significant association of the pre-miR-27a polymorphism with the risk of having a high alcohol intake (> 2 drinks/day in men and > 1 in women): 5.9\% in AA versus 17.5\% in GG; p(adjusted) < 0.001. In the sensitivity analysis, this association was homogeneous for sex, obesity and Mediterranean diet adherence. In conclusion, we report for the first time a significant association between a miRNA polymorphism (rs895819) and daily alcohol consumption.This study was funded, by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economia y Competitividad-Fondo Europeo de Desarrollo Regional (Projects CNIC-06/2007, RTIC G03/140, CIBER 06/03, PI06-1326, PI07-0954, PI11/02505, SAF2009-12304, AGL2010-22319-C03-03 and PRX14/00527), by the lUniversity Jaume I (Project P1-1B2013-54), by Contracts 53-K06-5-10 and 58-1950-9-001 from the U.S. Department of Agriculture Research Service, USA, by the Generalitat Valenciana (ACOMP2010-181, AP111/10, AP-042/11, ACOM2011/145, ACOMP/2012/190, ACOMP/2013/159 and ACOMP/213/165), and with the collaboration of the Real Colegio Complutense at Harvard University, Cambridge. MA, USA. Rocio Barragon's contract is funded by the Ayudas para la contratacion de personal investigador en formacion de caracter predoctoral, Programa ``VALencia Investigacion mas Desarrollo´´ (VALi+d). Conselleria d'Educacio, Investigacio, Cultura i Esport. Generalitat Valenciana, Spain (ACIF/2013/168).S