Abstract

Abstract Background Evidence suggests that red wine (RW) components can influence favorably gut microbiota. However, Interactions of RW, gut microbiota and plasma metabolomics remain unclear. Purpose The goal of this study was to assess the effects upon gut microbiota and plasma metabolomic profile of short-term, moderate RW intake in patients (pts) with documented coronary artery disease (CAD) Methods Forty-two males aged 60.4±5.4 years (SD) with documented CAD by angiography underwent a randomized, crossover, controlled, interventional trial. They were assigned to either RW treatment or abstinence from any alcoholic beverage, as control. Each treatment was preceded by a 2-week washout period. During the RW intervention, subjects ingested 250 ml of RW per day/ 5 days a week/ 3 weeks. Fasting blood samples and fecal samples were collected 4 times, after washout and at the end of each 3-week intervention. Gut microbiota was analysed by 16 S rRNA gene sequences and plasma metabolomics was performed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy. Twenty pts chosen randomly had their global metabolic profiles examined at all visits. Diet was carefully controlled and quantified by a 3 day/week questionnaire at beginning and end of the study. Prebiotics, probiotics were not allowed during the study. Patients in need for antibiotic therapy were not included. Results In the RW period compared to abstinence, fecal metagenomic revealed a decrease in abundance of Collinsella, a bacterial genus correlated with atherosclerosis; an increase in Eubacterium, genus related to fiber digestion and bile acid metabolism; and a significant increase in alpha diversity (p<0.05 for all). In plasma, trimethylamine N-oxide (TMAO), fell non-significantly post RW consumption. HDL and resveratrol increased after RW consumption (p<0.05). Plasma metabolomic analysis of 20 pts revealed microbiome related changes associated with RW consumption: decreased levels of phenylalanine, benzoate, tyrosine and tryptophan; lower levels of primary bile acids (BA) cholate, taurocholate, and also secondary BA deoxycholate and lithocholate sulfate. In parallel, RW elevated androgenic steroids and decreased beta oxidation (p<0.05 for all). Simultaneously total energy, proteins, carbohydrates and fat components of the diet did not change significantly. Conclusions Moderate RW ingestion augmented microbiota diversity, increased the proportion of putative anti-atherosclerotic bacteria and influenced plasma metabolomics. RW influenced energy metabolism through gut microbiota related plasma changes in amino acids, nucleotide profile, bile acids, androgenic steroids and beta-oxidation. These findings furnish some novel insight into mechanisms whereby RW may mitigate atherosclerosis. Acknowledgement/Funding FAPESP (Fundacao de Amparo à Pesquisa do Estado de Sao Paulo), IBRAVIN (Instituto Brasileiro do Vinho), Banco Bradesco SA

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