The ellagitannin composition and the total content of ellagitannins in different types of tea were studied by high-performance liquid chromatography/ion-trap mass spectrometry. Strictinin and seven ...other isomers, tellimagrandin I, and ellagic acid were identified from tea infusions. The ellagitannin content in tea infusions was determined after acid hydrolysis and ranged from 0.15 to 4.46 mg of ellagic acid equivalent/g of tea in the infusions. The intake of ellagic acid after drinking a cup of tea brewed with 4 g of tea could range between 0.59 and 17.89 mg. These results indicate that tea can be a significant contributor to the dietary intake of ellagitannins. Urolithins, the gut microbiota metabolites produced in vivo from ellagic acid and ellagitannins, were detected in human urine after dietary tea beverage intake. Urolithin metabotypes A, B, and 0 were identified in volunteers after tea intake. These results suggest that the daily intake of ellagitannins from tea can have a role in tea health effects.
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(Poly)phenols (PPs) constitute a large family of phytochemicals with high chemical diversity that are known to be active principles of plant-derived nutraceuticals and herbal ...medicinal products. Their pharmacological activity, however, is difficult to demonstrate due to their mild physiological effects, and to the large inter-individual variability observed. Many PPs have little bioavailability and reach the colon almost unaltered. There they encounter the gut microbes resulting in a two-way interaction in which PPs modulate the gut microbiota composition, and the intestinal microbes catabolize the ingested PPs to release metabolites that are often more active and better absorbed than the native phenolic compounds. The type and quantity of the PP metabolites produced in humans depend on the gut microbiota composition and function, and different metabotypes have been identified. However, not all the metabolites have the same biological activity, and therefore the final health effects of dietary PPs depend on the gut microbiota composition. Stratification in clinical trials according to individuals’ metabotypes is necessary to fully understand the health effects of PPs. In this review, we present and discuss the most significant and updated knowledge regarding the reciprocal interrelation of the gut microbiota with dietary PPs as a key factor that modulates the health effects of these compounds. The review will focus in those PPs that are known to be metabolized by gut microbiota resulting in bioactive metabolites.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Dietary phenolic compounds are often transformed before absorption. This transformation modulates their biological activity. Different studies have been carried out to understand gut microbiota ...transformations of particular polyphenol types and identify the responsible microorganisms. Although there are potentially thousands of different phenolic compounds in the diet, they are typically transformed to a much smaller number of metabolites. The aim of this review was to discuss the current information about the microbial degradation metabolites obtained from different phenolics and their formation pathways, identifying their differences and similarities. The modulation of gut microbial population by phenolics was also reviewed in order to understand the two-way phenolic−microbiota interaction. Clostridium and Eubacterium genera, which are phylogenetically associated, are other common elements involved in the metabolism of many phenolics. The health benefits from phenolic consumption should be attributed to their bioactive metabolites and also to the modulation of the intestinal bacterial population.
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Urolithins are dibenzob,dpyran‐6‐one derivatives that are produced by the human gut microbiota from ellagitannins and ellagic acid (EA). These metabolites are much better absorbed than their ...precursors and have been suggested to be responsible for the health effects attributed to ellagitannins and EA that occur in food products as berries and nuts. In the present review, the role and potential of urolithins in human health are critically reviewed, and a perspective of the research approach needed to demonstrate these health effects is presented, based on the existing knowledge. The analytical methods available for urolithin analysis, their occurrence in different tissues and biological fluids, and their metabolism by human gut microbiota are considered. In addition, the interindividual variability observed for the production of urolithins (metabotypes) and its relationship with health status and dysbiosis are also reviewed. The potential mechanisms of action of urolithins are also critically discussed, paying attention to the concentration and the type of metabolites used in the in vitro and in vivo assays and the physiological significance of the results obtained. The gut microbiota metabolism of EA to urolithins and that of daidzein to equol, their individual variations, and the effects on health are also compared.
The role of urolithins in human health after the consumption of dietary ellagitannins (ETs) is reviewed. The review shows preclinical evidence and in vitro mechanistic studies indicating that ETs can have anti‐inflammatory effects. However, no clinical studies have confirmed this effect yet. The recent finding that urolithins can reach the brain has increased the relevance of preclinical studies indicating that urolithins might have a role in protecting against neurodegenerative diseases.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research ...suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin‐rich sources (pomegranates, walnuts, strawberries, etc.). Here, this study comprehensively updates the knowledge on urolithins, emphasizing the review of the literature published during the last 5 years. To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues). There has been a substantial advance in the research on microorganisms involved in urolithin production, along with the compositional and functional characterization of the gut microbiota associated with urolithins metabolism that gives rise to the so‐called urolithin metabotypes (UM‐A, UM‐B, and UM‐0), relevant in human health. The design of in vitro studies using physiologically relevant assay conditions (molecular forms and concentrations) is still a pending subject, making some reported urolithin activities questionable. In contrast, remarkable progress has been made in the research on the safety, bioactivity, and associated mechanisms of urolithin A, including the first human interventions.
About 20 years ago, urolithins are discovered as bioavailable metabolites produced by the human gut microbiota from ellagitannins and ellagic acid. Pioneering investigations suggested pleiotropic effects for urolithins that growing evidence confirms, especially for urolithin A. Here, we update the knowledge on urolithins metabolism, bioactivity, and associated gut microbiota, emphasizing the literature published in the last 5 years.
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Three phenotypes for urolithin production after ellagitannin and ellagic acid intake are consistently observed in different human intervention trials. Subjects can be stratified into three ...urolithin-producing groups. “Phenotype A” produced only urolithin A conjugates, which included between 25 and 80% of the volunteers in the different trials. “Phenotype B” produced isourolithin A and/or urolithin B in addition to urolithin A, this being the second relevant group (10–50%). “Phenotype 0” (5–25%) was that in which these urolithins were not detected. The three phenotypes were observed independently of the volunteers’ health status and demographic characteristics (age, gender, body mass index (BMI)) and of the amount or type of ellagitannin food source ingested (walnuts and other nuts, strawberries, raspberries, and other berries or pomegranates). Interestingly, a higher percentage of phenotype B was observed in those volunteers with chronic illness (metabolic syndrome or colorectal cancer) associated with gut microbial imbalance (dysbiosis). These urolithin phenotypes could show differences in the human gut microbiota and should be considered in intervention trials dealing with health benefits of ellagitannins or ellagic acid. Whether this phenotypic variation could be a biomarker related to differential health benefits or illness predisposition deserves further research.
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Lettuce is one of the most commonly consumed leafy vegetables worldwide and is available throughout the entire year. Lettuce is also a significant source of natural phytochemicals. These compounds, ...including glycosylated flavonoids, phenolic acids, carotenoids, the vitamin B groups, ascorbic acid, tocopherols, and sesquiterpene lactones, are essential nutritional bioactive compounds. This review aims to provide a comprehensive understanding of the composition of health‐promoting compounds in different types of lettuce, the potential health benefits of lettuce in reducing the risks of chronic diseases, and the effect of preharvest and postharvest practices on the biosynthesis and accumulation of health‐promoting compounds in lettuce.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
During the 5th International Conference on Polyphenols and Health that was held in Sitges (Spain) in October 2011, the latest advances in this area of active research were presented. Sessions on ...polyphenol effects on cardiovascular disease, polyphenols as ingredients of functional foods, the role of polyphenols in preventing obesity and diabetes, the interaction of polyphenols with gut microbiota, bioavailability and metabolism of polyphenols in humans, the mechanisms of action of these metabolites in different models, new methodologies for the study of the role of polyphenols in health, polyphenols and cancer, recent developments in phenolic compounds and neuroscience, and polyphenols in epidemiology and public health were organized. This highlight issue presents a selection of papers from invited speakers, oral presentations, and poster prize winners. The perspectives for this exciting area of very active research were also discussed at the meeting and are summarized in this introductory paper.
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Although deficiencies in polyphenol intake do not result in specific deficiency diseases, adequate intake of polyphenols could confer health benefits, especially with regard to chronic diseases. Tea, ...cocoa, fruits, and berries, as well as vegetables, are rich in polyphenols. Flavan-3-ols from cocoa have been found to be associated with a reduced risk of stroke, myocardial infarction, and diabetes, as well as improvements in lipids, endothelial-dependent blood flow and blood pressure, insulin resistance, and systemic inflammation. The flavonoid quercetin and the stilbene resveratrol have also been associated with cardiometabolic health. Although polyphenols have been associated with improved cerebral blood flow, evidence of an impact on cognition is more limited. The ability of dietary polyphenols to produce clinical effects may be due, at least in part, to a bi-directional relationship with the gut microbiota. Polyphenols can impact the composition of the gut microbiota (which are independently associated with health benefits), and gut bacteria metabolize polyphenols into bioactive compounds that produce clinical benefits. Another critical interaction is that of polyphenols with other phytochemicals, which could be relevant to interpreting the health parameter effects of polyphenols assayed as purified extracts, whole foods, or whole food extracts.
Scope
The pomegranate lipid‐lowering properties remain controversial, probably due to the interindividual variability in polyphenol (ellagitannins) metabolism.
Objective
We aimed at investigating ...whether the microbially derived ellagitannin‐metabolizing phenotypes, i.e. urolithin metabotypes A, (UM‐A), B (UM‐B), and 0 (UM‐0), influence the effects of pomegranate extract (PE) consumption on 18 cardiovascular risk biomarkers in healthy overweight‐obese individuals.
Methods and results
A double‐blind, crossover, dose–response, randomized, placebo‐controlled trial was conducted. The study (POMEcardio) consisted of two test phases (dose‐1 and dose‐2, lasting 3 weeks each) and a 3‐week washout period between each phase. Forty‐nine participants (BMI > 27 kg/m2) daily consumed one (dose‐1, 160 mg phenolics/day) or four (dose‐2, 640 mg phenolics/day) PE or placebo capsules. Notably, UM‐B individuals showed the highest baseline cardiovascular risk. After dose‐2, total cholesterol (–15.5 ± 3.7%), LDL‐cholesterol (–14.9 ± 2.1%), small LDL‐cholesterol (–47 ± 7%), non‐HDL‐cholesterol (–11.3 ± 2.5%), apolipoprotein‐B (–12 ± 2.2%), and oxidized LDL‐cholesterol –24 ± 2.5%) dose dependently decreased (P < 0.05) but only in UM‐B subjects. These effects were partially correlated with urolithin production and the increase in Gordonibacter levels. Three (50%) nonproducers (UM‐0) became producers following PE consumption.
Conclusions
UM clustering suggests a personalized effect of ellagitannin‐containing foods and could explain the controversial pomegranate benefits. Research on the specific role of urolithins and the microbiota associated with each UM is warranted.
The high interindividual variability prevents the improvement of serum cardiovascular disease risk markers in healthy overweight‐obese subjects following pomegranate supplementation. However, urolithin metabotype clustering reveales a significant improvement of the blood lipid profile only in urolithin metabotype B individuals. This suggests a personalized effect of ellagitannin‐containing foods and could explain the controversial pomegranate benefits and the lack of European Food Safety Authority related health claims.
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