Scientists have uncovered how gut-derived compounds in urine can reveal red wine’s anti-inflammatory effects—offering a more accurate way to link diet to heart health.
Short Communication: Microbiota-derived resveratrol metabolites: New biomarkers of red wine consumption are inversely associated with inflammation in a longitudinal study of a Mediterranean population. Image Credit: givaga / Shutterstock
In a recent study published in The Journal of Nutrition, researchers in Spain assessed whether microbiota-derived resveratrol metabolites in urine can reliably indicate red wine consumption and its association with systemic inflammation.
Background
Can a glass of red wine a day really be good for you? Red wine contains resveratrol, a plant-based (poly)phenol believed to reduce inflammation and protect against cardiovascular disease. However, dietary studies often rely on self-reported food frequency questionnaires (FFQs), which are prone to recall bias and inaccuracies, especially when reporting alcohol intake. While moderate red wine consumption has been linked to anti-inflammatory benefits in some studies, results are inconsistent. Biomarkers could provide a more objective method for assessing intake and its health impact. Further research is needed to identify specific, reliable biomarkers that reflect red wine consumption and its biological effects.
About the study
This longitudinal study analyzed 179 older adults at high cardiovascular risk from the Prevención con Dieta Mediterránea (PREDIMED) trial. Participants were monitored over one year. Food intake was measured using validated semi-quantitative FFQs. Adherence to the Mediterranean diet was assessed using a 14-point screener, while physical activity was evaluated with the Minnesota Leisure Time Physical Activity Questionnaire, expressed in metabolic equivalent tasks (METs) minutes per day.
Plasma levels of five inflammatory markers—soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1)—were measured using Luminex-based (Multi-Analyte Profiling) xMAP technology. Urinary levels of microbiota-derived dihydroresveratrol glucuronide (DHRg) and dihydroresveratrol sulfate (DHRs) were quantified using high-performance liquid chromatography with mass spectrometry.
Statistical analyses included receiver operating characteristic (ROC) curves to test how well urinary metabolites predicted red wine intake. Linear regressions examined the associations between metabolite levels and inflammation, adjusting for confounders such as age, sex, physical activity, medication use, and dietary factors, including extra-virgin olive oil and omega-3 fatty acids.
Study results
The average participant was 69 years old, and nearly half were women. Common risk factors included overweight status (91%), hypertension (82%), dyslipidemia (65%), and diabetes (50%). Red wine intake averaged 62.1 mL per day, and urinary concentrations of DHRg and DHRs were 1.1 and 1.6 nmol/mL, respectively.
ROC analyses demonstrated that both urinary metabolites were strong indicators of red wine consumption. The adjusted area under the curve (AUC) was 0.835 for DHRg and 0.803 for DHRs, highlighting their accuracy as specific biomarkers. In contrast, white wine consumption showed no significant association with these metabolites, emphasizing their specificity for red wine.
Importantly, higher baseline levels of DHRs in urine were significantly associated with lower concentrations of sVCAM-1 in plasma, a biomarker implicated in atherosclerosis (−0.40 ng/mL per 1 standard deviation increase, p = 0.012). Over the course of one year, increases in urinary DHRg were also associated with greater reductions in sVCAM-1 levels (−0.43 ng/mL per 1 standard deviation increase, p = 0.016). No significant associations were found between these metabolites and other inflammatory markers, such as IL-6, TNF-α, sICAM-1, or MCP-1.
Interestingly, when researchers relied solely on FFQ-reported red wine intake, no significant associations with any inflammatory biomarkers were observed, i.e., either at baseline or after one year. Even in cases where trends were present, such as with sVCAM-1, they did not reach statistical significance. This discrepancy emphasizes the limitations of FFQs and the value of objective, biologically derived biomarkers.
The findings highlight that resveratrol from red wine is metabolized by gut microbiota into DHRg and DHRs, which can be reliably detected in urine. These compounds reflect actual intake more accurately than self-reported data and are inversely linked to inflammation. Notably, the ability of red wine polyphenols to potentially suppress the expression of vascular cell adhesion molecules at the gene level, as seen in prior molecular studies, may explain this effect.
These results are particularly relevant for aging populations at cardiovascular risk, where managing chronic inflammation is key to prevention. Furthermore, the specificity of the metabolites to red wine allows differentiation from other alcoholic beverages, offering a novel tool for nutritional and public health research.
Conclusions
To summarize, urinary dihydroresveratrol glucuronide and sulfate, derived from the gut microbiota’s metabolism of red wine resveratrol, have been identified as specific and reliable biomarkers of red wine consumption. Their presence was inversely associated with plasma levels of soluble vascular cell adhesion molecule-1, a marker of inflammation linked to atherosclerosis. These findings underscore the potential health benefits of light to moderate red wine intake within a Mediterranean dietary context. More importantly, they highlight the limitations of FFQs and the importance of using biological markers to assess diet-disease relationships. This work supports future use of metabolite-based tools in personalized nutrition and public health strategies.
Journal reference:
- Francesc M. Campins-Machado, Rosa Casas, Rosa M. Lamuela-Raventós, et al. Microbiota-derived resveratrol metabolites: New biomarkers of red wine consumption are inversely associated with inflammation in a longitudinal study of a Mediterranean population, The Journal of Nutrition (2025), DOI: 10.1016/j.jnha.2025.100542, https://www.sciencedirect.com/science/article/pii/S1279770725000661