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Article

Systematic Bioinformatic Analyses of Nutrigenomic Modifications by Polyphenols Associated with Cardiometabolic Health in Humans—Evidence from Targeted Nutrigenomic Studies

1
Faculty of Medical Sciences, Goce Delcev University, 2000 Stip, North Macedonia
2
Institute for Adriatic Crops and Karst Reclamation, 21000 Split, Croatia
3
Unité de Nutrition Humaine (UNH), Université Clermont Auvergne, Institut National de Recherche pour L’agriculture, L’alimentation et L’environnement (INRAE), Faculté de Médecine, F-63000 Clermont-Ferrand, France
4
Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
5
Nutrigenomics Research Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, 43007 Tarragona, Spain
6
Department of Medicine, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece
7
Department of Food Science, Czech University of Life Sciences, 16521 Prague, Czech Republic
8
Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
9
Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
10
National Research Council (CNR) Institute of Clinical Physiology (IFC), 73100 Lecce, Italy
11
Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK
12
Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California Davis, Davis, CA 95616, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Maria Annunziata Carluccio
Nutrients 2021, 13(7), 2326; https://doi.org/10.3390/nu13072326
Received: 17 May 2021 / Revised: 25 June 2021 / Accepted: 30 June 2021 / Published: 6 July 2021
Cardiometabolic disorders are among the leading causes of mortality in the human population. Dietary polyphenols exert beneficial effects on cardiometabolic health in humans. Molecular mechanisms, however, are not completely understood. Aiming to conduct in-depth integrative bioinformatic analyses to elucidate molecular mechanisms underlying the protective effects of polyphenols on cardiometabolic health, we first conducted a systematic literature search to identify human intervention studies with polyphenols that demonstrate improvement of cardiometabolic risk factors in parallel with significant nutrigenomic effects. Applying the predefined inclusion criteria, we identified 58 differentially expressed genes at mRNA level and 5 miRNAs, analyzed in peripheral blood cells with RT-PCR methods. Subsequent integrative bioinformatic analyses demonstrated that polyphenols modulate genes that are mainly involved in the processes such as inflammation, lipid metabolism, and endothelial function. We also identified 37 transcription factors that are involved in the regulation of polyphenol modulated genes, including RELA/NFKB1, STAT1, JUN, or SIRT1. Integrative bioinformatic analysis of mRNA and miRNA-target pathways demonstrated several common enriched pathways that include MAPK signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, focal adhesion, or PPAR signaling pathway. These bioinformatic analyses represent a valuable source of information for the identification of molecular mechanisms underlying the beneficial health effects of polyphenols and potential target genes for future nutrigenetic studies. View Full-Text
Keywords: systematic literature search; nutrigenomics; integrative bioinformatics; polyphenols; cardiometabolic health; human systematic literature search; nutrigenomics; integrative bioinformatics; polyphenols; cardiometabolic health; human
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MDPI and ACS Style

Ruskovska, T.; Budić-Leto, I.; Corral-Jara, K.F.; Ajdžanović, V.; Arola-Arnal, A.; Bravo, F.I.; Deligiannidou, G.-E.; Havlik, J.; Janeva, M.; Kistanova, E.; Kontogiorgis, C.; Krga, I.; Massaro, M.; Miler, M.; Milosevic, V.; Morand, C.; Scoditti, E.; Suárez, M.; Vauzour, D.; Milenkovic, D. Systematic Bioinformatic Analyses of Nutrigenomic Modifications by Polyphenols Associated with Cardiometabolic Health in Humans—Evidence from Targeted Nutrigenomic Studies. Nutrients 2021, 13, 2326. https://doi.org/10.3390/nu13072326

AMA Style

Ruskovska T, Budić-Leto I, Corral-Jara KF, Ajdžanović V, Arola-Arnal A, Bravo FI, Deligiannidou G-E, Havlik J, Janeva M, Kistanova E, Kontogiorgis C, Krga I, Massaro M, Miler M, Milosevic V, Morand C, Scoditti E, Suárez M, Vauzour D, Milenkovic D. Systematic Bioinformatic Analyses of Nutrigenomic Modifications by Polyphenols Associated with Cardiometabolic Health in Humans—Evidence from Targeted Nutrigenomic Studies. Nutrients. 2021; 13(7):2326. https://doi.org/10.3390/nu13072326

Chicago/Turabian Style

Ruskovska, Tatjana, Irena Budić-Leto, Karla F. Corral-Jara, Vladimir Ajdžanović, Anna Arola-Arnal, Francisca I. Bravo, Georgia-Eirini Deligiannidou, Jaroslav Havlik, Milkica Janeva, Elena Kistanova, Christos Kontogiorgis, Irena Krga, Marika Massaro, Marko Miler, Verica Milosevic, Christine Morand, Egeria Scoditti, Manuel Suárez, David Vauzour, and Dragan Milenkovic. 2021. "Systematic Bioinformatic Analyses of Nutrigenomic Modifications by Polyphenols Associated with Cardiometabolic Health in Humans—Evidence from Targeted Nutrigenomic Studies" Nutrients 13, no. 7: 2326. https://doi.org/10.3390/nu13072326

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