Novel multimetabolite prediction of walnut consumption by a urinary biomarker model in a free-living population: the PREDIMED study.
The beneficial impact of walnuts on human health has been attributed to their unique chemical composition. In order to characterize the dietary walnut fingerprinting, spot urine samples from two sets of 195 (training) and 186 (validation) individuals were analyzed by an HPLC-q-ToF-MS untargeted metabolomics approach, selecting the most discriminating metabolites by multivariate data analysis (VIP ≥ 1.5). Stepwise logistic regression analysis was used to design a multimetabolite prediction biomarker model. The global performance of the model and each included metabolite in it was evaluated by receiver operating characteristic curves, using the area under the curve (AUC) values. Dietary expos…
A metabolomics-driven approach to predict cocoa product consumption by designing a multimetabolite biomarker model in free-living subjects from the PREDIMED study
Scope The aim of the current study was to apply an untargeted metabolomics strategy to characterize a model of cocoa intake biomarkers in a free-living population. Methods and results An untargeted HPLC-q-ToF-MS based metabolomics approach was applied to human urine from 32 consumers of cocoa or derived products (CC) and 32 matched control subjects with no consumption of cocoa products (NC). The multivariate statistical analysis (OSC-PLS-DA) showed clear differences between CC and NC groups. The discriminant biomarkers identified were mainly related to the metabolic pathways of theobromine and polyphenols, as well as to cocoa processing. Consumption of cocoa products was also associated wit…
Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota
Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated wit…
The 3-year effect of the mediterranean diet intervention on inflammatory biomarkers related to cardiovascular disease
The intervention with the Mediterranean diet (MD) pattern has evidenced short-term anti-inflammatory effects, but little is known about its long-term anti-inflammatory properties at molecular level. This study aims to investigate the 3-year effect of MD interventions compared to low-fat diet (LFD) on changes on inflammatory biomarkers related to atherosclerosis in a free-living population with a high-risk of cardiovascular disease (CD). Participants (n = 285) in the PREDIMED trial were randomly assigned into three intervention groups: MD with extra-virgin olive oil (EVOO) or MD-Nuts, and a LFD. Fourteen plasma inflammatory biomarkers were determined by Luminex assays. An additional pilot st…
Non-targeted metabolomic biomarkers and metabotypes of type 2 diabetes: A cross-sectional study of PREDIMED trial participants
Aim. - To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D. Methods. - A metabolomics analysis using the 1 H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively. Metabotypes associated with T2D were identified using the k-means algorithm. Results. - A …
Gut and microbial resveratrol metabolite profiling after moderate long-term consumption of red wine versus dealcoholized red wine in humans by an optimized ultra-high-pressure liquid chromatography tandem mass spectrometry method
Resveratrol exerts a variety of biological and pharmacological activities, which are observed despite its extremely low bioavailability and rapid clearance from the circulation due to extensive sulfation and glucuronidation in the intestine and liver. In order to more accurately quantify all known resveratrol metabolites, a sensitive and optimized analytical assay was developed and validated by pure standards. Methodology improvements aimed to the chromatographic detection of disulfates and sulfoglucuronides, improving resolution of sulfates, by using a buffered solution, with recovery values of resveratrol and its metabolites, even of sulfates, of 99%. The adapted methodology was then appl…
Urinary 1H Nuclear Magnetic Resonance Metabolomic Fingerprinting Reveals Biomarkers of Pulse Consumption Related to Energy-Metabolism Modulation in a Subcohort from the PREDIMED study
Little is known about the metabolome fingerprint of pulse consumption. The study of robust and accurate biomarkers for pulse dietary assessment has great value for nutritional epidemiology regarding health benefits and their mechanisms. To characterize the fingerprinting of dietary pulses (chickpeas, lentils and beans), spot urine samples from a subcohort from the PREDIMED study were stratified, using a validated food frequency questionnaire. Non-pulse consumers (≤ 4 g/day of pulse intake) and habitual pulse consumers (≥ 25 g/day of pulse intake) were analysed using a 1H-NMR metabolomics approach combined with multi- and univariate data analysis. Pulse consumption showed differences through…
Phenolic and microbial-targeted metabolomics to discovering and evaluating wine intake biomarkers in human urine and plasma
The discovery of biomarkers of intake in nutritional epidemiological studies is essential in establishing an association between dietary intake (considering their bioavailability) and diet-related risk factors for diseases. The aim is to study urine and plasma phenolic and microbial profile by targeted metabolomics approach in a wine intervention clinical trial for discovering and evaluating food intake biomarkers. High-risk male volunteers (n = 36) were included in a randomized, crossover intervention clinical trial. After a washout period, subjects received red wine or gin, or dealcoholized red wine over four weeks. Fasting plasma and 24-h urine were collected at baseline and after each i…
Metabolomic Pattern Analysis after Mediterranean Diet Intervention in a Nondiabetic Population: A 1- and 3-Year Follow-up in the PREDIMED Study
The Mediterranean diet (MD) is considered a dietary pattern with beneficial effects on human health. The aim of this study was to assess the effect of an MD on urinary metabolome by comparing subjects at 1 and 3 years of follow-up, after an MD supplemented with either extra-virgin olive oil (MD + EVOO) or nuts (MD + Nuts), to those on advice to follow a control low-fat diet (LFD). Ninety-eight nondiabetic volunteers were evaluated, using metabolomic approaches, corresponding to MD + EVOO (n = 41), MD + Nuts (n = 27), or LFD (n = 30) groups. The (1)H NMR urinary profiles were examined at baseline and after 1 and 3 years of follow-up. Multivariate data analysis (OSC-PLS-DA and HCA) methods we…
Total polyphenol excretion and blood pressure in subjects at high cardiovascular risk.
Background and aims Dietary factors are critical for the prevention and treatment of hypertension, but data on the effects of specific nutrients on blood pressure (BP) are scarce. The aim of this study was to assess the relationship between total polyphenol excretion (TPE) in urine, as an objective measurement of total polyphenol intake and BP in an elderly population at high cardiovascular risk. Methods and results Cross-sectional substudy of 589 high-risk participants entering in the PREDIMED trial. BP was measured and TPE was determined in urine by Folin–Ciocalteu assay. A significant positive association was observed between TPE in urine and daily intake of fruit and vegetables (F&V), c…
Microbial metabolomic fingerprinting in urine after regular dealcoholized red wine consumption in humans.
The regular consumption of dealcoholized red wine (DRW) has demonstrated benefits in cardiovascular risk factors. The analysis of phenolic metabolites formed in the organism, especially those that could come from microbiota metabolism, would help to understand these benefits. The aim of this study was to determine the widest urinary metabolomic fingerprinting of phenolics and microbial-derived phenolic acids (n = 61) after regular intake of DRW in men at high cardiovascular risk by UPLC-MS/MS using a targeted approach. Up to 49 metabolites, including phase II and microbial phenolic metabolites, increased after DRW consumption compared to baseline (P < 0.05). The highest percentage of increa…
Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: a randomized clinical trial.
Summary Background & aims Epidemiological data suggest that moderate red wine consumption reduces cardiovascular mortality and the incidence of diabetes. However, whether these effects are due to ethanol or to non-alcoholic components of red wine still remains unknown. The aim of the present study was to compare the effects of moderate consumption of red wine, dealcoholized red wine, and gin on glucose metabolism and the lipid profile. Methods Sixty-seven men at high cardiovascular risk were randomized in a crossover trial. After a run-in period, all received each of red wine (30 g alcohol/d), the equivalent amount of dealcoholized red wine, and gin (30 g alcohol/d) for 4 week periods, in a…