Microbiota-derived resveratrol metabolites: new biomarkers of red wine consumption are inversely associated with inflammation in a longitudinal study of a Mediterranean population

Abstract

Objectives: </strong>To evaluate the association between urinary microbiota-derived resveratrol metabolites, which may serve as specific biomarkers of red wine consumption, and plasma circulating proinflammatory markers.<span style="color:red"> </span><strong>Design, settings, and participants:</strong> One-year longitudinal study included 179 participants at high cardiovascular risk (mean age 69 years, 49% women) enrolled in the PREDIMED trial. <strong>Measurements: </strong>Plasma inflammatory biomarkers and urinary microbiota-derived resveratrol metabolites were analyzed using xMAP technology and high-performance liquid chromatography coupled to mass spectrometry, respectively. Receiver operating characteristic (ROC) analyses were performed to evaluate the reliability of urine resveratrol metabolites as biomarkers of red wine consumption, as reported in the food frequency questionnaires (FFQs) of the participants. The relationship between baseline values and 1-year changes in urinary microbiota-derived resveratrol metabolites and plasma levels of circulating inflammatory molecules were assessed. <strong>Results:</strong> ROC curves confirmed that urinary dihydroresveratrol glucuronide (DHRg) [AUC = 0.835] and sulfate (DHRs) [AUC = 0.803] metabolites are reliable and specific biomarkers of red wine consumption. Baseline urinary concentrations of DHRs were negatively associated with plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) (-0.40 ng/mL per 1-SD increase, <em>p</em> = 0.012). After one year of follow-up, changes in urinary concentrations of DHRg also showed a negative association with plasma circulating sVCAM-1 levels (-0.39 ng/mL per 1-SD increase, p-value = 0.028). No significant associations were detected at baseline and after one year of follow-up when FFQ information of red wine consumption was used to perform the regression analysis with circulating inflammatory molecules. <strong>Conclusions:</strong> Light to moderate red wine consumption (10 to 20 grams of alcohol per day), which can be monitored by microbiota-derived resveratrol metabolites excreted in urine, is associated with lower plasma concentrations of sVCAM-1, an inflammatory biomarker related to atherosclerosis. Biomarkers of consumption offer advantages compared to FFQ data, since they provide objective and more accurate information about nutrient intake and metabolism. Without specific biomarkers of red wine consumption, no significant associations would have been found in the present study.