Cardiovascular and metabolic disorders present major causes of mortality in the ageing population. Polyphenols present in human diets possess cardiometabolic protective properties, however their underlying molecular mechanisms in humans are still not well identified. Even though preclinical and in vitro studies advocate that these bioactives can modulate gene expression, most studies were performed using targeted approaches. With the objective to decipher the molecular mechanisms underlying polyphenols cardiometabolic preventive properties in humans, we performed integrative multi-omic bioinformatic analyses of published studies which reported improvements of cardiometabolic risk factors following polyphenol intake, together with genomic analyses performed using untargeted approach. We identified 5 studies within our criteria and nearly 5000 differentially expressed genes, both mRNAs and miRNAs, in peripheral blood cells. Integrative bioinformatic analyses (e.g. pathway and gene network analyses, identification of transcription factors, correlation of gene expression profiles with those associated with diseases and drug intake) revealed that these genes are involved in the processes such as cell adhesion and mobility, immune system, metabolism, or cell signaling. We also identified 27 miRNAs known to regulate processes such as cell cytoskeleton, chemotaxis, cell signaling, or cell metabolism. Gene expression profiles negatively correlated with expression profiles of cardiovascular disease patients, while a positive correlation was observed with gene expression profiles following intake of drugs against cardiometabolic disorders. These analyses further advocate for health protective effects of these bioactives against age-associated diseases. In conclusion, polyphenols can exert multi-genomic modifications in humans and use of untargeted methods coupled with bioinformatic analyses represent the best approach to decipher molecular mechanisms underlying healthy-ageing effects of these bioactives.

• Klíčová slova
• Bioinformatics, Cardiometabolic health, Genomics, Integrated multi-omics, Polyphenols,
• MeSH
• kardiovaskulární nemoci * genetika   prevence a kontrola   MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nutrigenomika MeSH
• polyfenoly farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• messenger RNA MeSH
• mikro RNA * MeSH
• polyfenoly MeSH

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.

• Klíčová slova
• cardiometabolic health, human, integrative bioinformatics, nutrigenomics, polyphenols, systematic literature search,
• MeSH
• dospělí MeSH
• fyziologie výživy genetika   MeSH
• kardiometabolické riziko MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA krev   MeSH
• metabolický syndrom genetika   prevence a kontrola   MeSH
• mikro RNA krev   MeSH
• nutrigenomika MeSH
• ochranné látky farmakologie   MeSH
• polyfenoly farmakologie   MeSH
• signální transdukce genetika   MeSH
• výpočetní biologie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH
• Názvy látek
• messenger RNA MeSH
• mikro RNA MeSH
• ochranné látky MeSH
• polyfenoly MeSH