The role of grapes on cardiovascular, brain and gut health: underlying mechanisms of action using multigenomic approach and assessment of difference in response between man and woman

• Grant number: 23/17883-4
• Support Opportunities: Scholarships abroad - Research
• Start date: January 10, 2025
• End date: December 09, 2025
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Mário Roberto Maróstica Junior
• Grantee: Mário Roberto Maróstica Junior
• Host Investigator: Dragan Milenkovic
• Host Institution: Faculdade de Engenharia de Alimentos (FEA). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: North Carolina State University Plant For Human Health Institute, United States

Abstract

Increased incidence of obesity and a range of chronic diseases, notably type 2 diabetes and cardiovascular diseases (CVD) are strongly related to diet. Polyphenols may delay or prevent the progression of diet-induced chronic diseases. Mechanisms underlying the health properties of these bioactives have been shown to involve complex multigenomic regulation, that is regulation of expression of protein coding and non-coding genes, changes in DNA methylation or interactions with cell signaling proteins. A few studies have also suggested that bioactives or bioactive-rich foods can positively affect intestinal barrier by decreasing intestinal permeability and positively impact in gut microbiota reducing the growth of microorganisms associated with intestinal dysbiosis and increased the abundance of beneficial bacteria. Several studies showed that grape-derived products can improve cardiometabolic health. The objective of the proposed project is to demonstrate the capacity of California grape consumption to counteract changes in the gut microbiome and intestinal permeability in overweight subjects, together with systemic inflammation and vascular function, evaluating the underlying mechanisms of action using multigenomic approach as well as characterize potential differences in response between men and women. Specific objectives are: 1) Evaluate the effect of the grape on global metabolome in samples obtained from the clinical trials using untargeted metabolomics (WP1); 2) Investigate the response to daily intake for three weeks of grape on cardiometabolic risk factors (such as blood pressure, inflammation, lipid profiles), intestinal microbiome composition and intestinal permeability in overweight or obese individuals (WP2); 3) Model changes in gut microbiota and intestinal permeability with cardiometabolic risk factors, including inflammation, vascular function (vascular stiffness, blood pressure) and lipid profiles (WP3); 4) Examine differences in response to grape intake regarding gut microbiota composition, intestinal permeability, cardiometabolic and inflammatory markers between male and female volunteers (WP4); 5) Evaluate the capacity of circulating metabolites of grape polyphenols to maintain human brain endothelial cell permeability under inflammatory and lipid stress (WP5); 6. To evaluate the underlying mechanisms of action of grape polyphenols metabolites using multigenomic approach (WP6).