The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: Comparison between normoweight, overweight-obesity and metabolic syndrome.

Background & aims: Urolithins are microbial metabolites produced after consumption of ellagitannincontaining foods such as pomegranates and walnuts. Parallel to isoflavone-metabolizing phenotypes, ellagitannin-metabolizing phenotypes (urolithin metabotypes A, B and 0; UM-A, UM-B and UM-0, respectively) can vary among individuals depending on their body mass index (BMI), but correlations between urolithin metabotypes (UMs) and cardiometabolic risk (CMR) factors are unexplored. We investigated the association between UMs and CMR factors in individuals with different BMI and health status. Methods: UM was identified using UPLC-ESI-qToF-MS in individuals consuming pomegranate or nuts. The associations between basal CMR factors and the urine urolithin metabolomic signature were explored in 20 healthy normoweight individuals consuming walnuts (30 g/d), 49 healthy overweightobese individuals ingesting pomegranate extract (450 mg/d) and 25 metabolic syndrome (MetS) patients consuming nuts (15 g-walnuts, 7.5 g-hazelnuts and 7.5 g-almonds/d). Results: Correlations between CMR factors and urolithins were found in overweight-obese individuals. Urolithin-A (mostly present in UM-A) was positively correlated with apolipoprotein A-I (P 0.05) and intermediate-HDL-cholesterol (P 0.05) while urolithin-B and isourolithin-A (characteristic from UM-B) were positively correlated with total-cholesterol, LDL-cholesterol (P 0.001), apolipoprotein B (P 0.01), VLDL-cholesterol, IDL-cholesterol, oxidized-LDL and apolipoprotein B:apolipoprotein A-I ratio (P 0.05). In MetS patients, urolithin-A only correlated inversely with glucose (P 0.05). Statin-treated MetS patients with UM-A showed a lipid profile similar to that of healthy normoweight individuals while a poor response to lipid-lowering therapy was observed in MB patients. Conclusions: UMs are potential CMR biomarkers. Overweight-obese individuals with UM-B are at increased risk of cardiometabolic disease, whereas urolithin-A production could protect against CMR factors. Further research is warranted to explore these associations in larger cohorts and whether the effect of lipidlowering drugs or ellagitannin-consumption on CMR biomarkers depends on individuals' UM

Future prospects for dissecting inter-individual variability in the absorption, distribution and elimination of plant bioactives of relevance for cardiometabolic endpoints

PURPOSE: The health-promoting potential of food-derived plant bioactive compounds is evident but not always consistent across studies. Large inter-individual variability may originate from differences in digestion, absorption, distribution, metabolism and excretion (ADME). ADME can be modulated by age, sex, dietary habits, microbiome composition, genetic variation, drug exposure and many other factors. Within the recent COST Action POSITIVe, large-scale literature surveys were undertaken to identify the reasons and extent of inter-individual variability in ADME of selected plant bioactive compounds of importance to cardiometabolic health. The aim of the present review is to summarize the findings and suggest a framework for future studies designed to investigate the etiology of inter-individual variability in plant bioactive ADME and bioefficacy. RESULTS: Few studies have reported individual data on the ADME of bioactive compounds and on determinants such as age, diet, lifestyle, health status and medication, thereby limiting a mechanistic understanding of the main drivers of variation in ADME processes observed across individuals. Metabolomics represent crucial techniques to decipher inter-individual variability and to stratify individuals according to metabotypes reflecting the intrinsic capacity to absorb and metabolize bioactive compounds. CONCLUSION: A methodological framework was developed to decipher how the contribution from genetic variants or microbiome variants to ADME of bioactive compounds can be predicted. Future study design should include (1) a larger number of study participants, (2) individual and full profiling of all possible determinants of internal exposure, (3) the presentation of individual ADME data and (4) incorporation of omics platforms, such as genomics, microbiomics and metabolomics in ADME and efficacy studies

Addressing the inter-individual variation in response to consumption of plant food bioactives : Towards a better understanding of their role in healthy aging and cardiometabolic risk reduction

Bioactive compounds in plant-based foods have health properties that contribute to the prevention of age-related chronic diseases, particularly cardiometabolic disorders. Conclusive proof and understanding of these benefits in humans is essential in order to provide effective dietary recommendations but, so far, the evidence obtained from human intervention trials is limited and contradictory. This is partly due to differences between individuals in the absorption, distribution, metabolism and excretion of bioactive compounds, as well as to heterogeneity in their biological response regarding cardiometabolic health outcomes. Identifying the main factors underlying inter-individual differences, as well as developing new and innovative methodologies to account for such variability constitute an overarching goal to ultimately optimize the beneficial health effects of plant food bioactives for each and every one of us. In this respect, this position paper from the COST Action FA1403-POSITIVe examines the main factors likely to affect the individual responses to consumption of plant food bioactives and presents perspectives for assessment and consideration of inter-individual variability.Peer reviewe

Urolithins Are the Main Urinary Microbial-Derived Phenolic Metabolites Discriminating a Moderate Consumption of Nuts in FreeLiving Subjects with Diagnosed Metabolic Syndrome

Walnuts (Juglans regia L.), hazelnuts (Corylus avellana L.), and almonds (Prunus dulcis Mill.) are rich sources of ellagitannins and proanthocyanidins. Gut microbiota plays a crucial role in modulating the bioavailability of these high molecular weight polyphenols. However, to date there are no studies evaluating the capacity to produce nut phenolic metabolites in subjects with metabolic syndrome (MetS), a pathology associated with an altered gut bacterial diversity. This study applied a LC-MS targeted approach to analyze the urinary excretion of nut phenolic metabolites in MetS subjects following 12 weeks of nut consumption, compared to sex- and age-matched individuals given a nut-free control diet. Metabolites were targeted in both hydrolyzed and nonhydrolyzed urine by LC-PDA-QqQ-MS/MS analysis, and identification of metabolites lacking available standards was confirmed by LC-ESI-ITD-FT-MS. Ellagitannin-derived urolithins A and B significantly increased after the nutenriched-diet, urolithins C and D were also detected, and a complex combination of urolithin-conjugated forms was observed in nonhydrolyzed urine, confirming an extensive phase II metabolism after absorption. In contrast, no significant increases in proanthocyanidin microbial metabolites were observed in urine following nut consumption. Because the intestinal microbiota of the subjects in this study could catabolize ellagitannins into a wide range of urolithins, further research is strongly warranted on the in vivo potential of these microbial metabolites in reducing cardiometabolic risk

A Novel Integrative Methodology for Research on Pot-honey Variations During Post-harvest

This novel review of analytical methods for pot-honey research was intended to provide concise references to a 35-day post-harvest experiments at 30 °C, in an integrated study. Diverse methods were selected from specialized literature, from the AOAC (Association of Official Analytical Chemists), and the International Honey Commission. Besides the geographical and seasonal origin, the pot-honey I.D. consists of entomological and botanical identifications, the latter performed by acetolyzed or natural melissopalynology. The methods of this integrative study included: 1. Physicochemical analysis (Aw, color, moisture, pH, free acidity, lactone acidity, total acidity, hydroxymethylfurfural (HMF), and sugars by highperformance liquid chromatography HPLC), 2. Targeted proton nuclear magnetic resonance 1H-NMR metabolomics (sugars, ethanol, HMF, aliphatic organic acids, amino acids, and botanical markers), 3. Biochemical composition (flavonoids, polyphenols), 4. Antioxidant activity (ABTS 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid-free radical scavenging assay, DPPH 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, ferric reduction assay FRAP), 5. Microbial counts (aerobic plate, yeast and mold, Bacillus, and lactic acid bacteria count), 6. Honey microbiome profiling via independent-culture method: high-throughput bacteria and fungi based on amplicon sequencing approaches, 7. Sensory evaluation (odor, aroma, taste, persistence), and 8. Honey authenticity and biosurfactant tests by an interphase emulsion. A further section was included to provide basic information on the results obtained using each method. This was needed to explain the interacting components derived from pot-honey processing within the stingless bee nest and post-harvest transformations

A Novel Integrative Methodology for Research on Pot-honey Variations During Post-harvest

This novel review of analytical methods for pot-honey research was intended to provide concise references to a 35-day post-harvest experiments at 30 °C, in an integrated study. Diverse methods were selected from specialized literature, from the AOAC (Association of Official Analytical Chemists), and the International Honey Commission. Besides the geographical and seasonal origin, the pot-honey I.D. consists of entomological and botanical identifications, the latter performed by acetolyzed or natural melissopalynology. The methods of this integrative study included: 1. Physicochemical analysis (Aw, color, moisture, pH, free acidity, lactone acidity, total acidity, hydroxymethylfurfural (HMF), and sugars by highperformance liquid chromatography HPLC), 2. Targeted proton nuclear magnetic resonance 1H-NMR metabolomics (sugars, ethanol, HMF, aliphatic organic acids, amino acids, and botanical markers), 3. Biochemical composition (flavonoids, polyphenols), 4. Antioxidant activity (ABTS 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid-free radical scavenging assay, DPPH 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, ferric reduction assay FRAP), 5. Microbial counts (aerobic plate, yeast and mold, Bacillus, and lactic acid bacteria count), 6. Honey microbiome profiling via independent-culture method: high-throughput bacteria and fungi based on amplicon sequencing approaches, 7. Sensory evaluation (odor, aroma, taste, persistence), and 8. Honey authenticity and biosurfactant tests by an interphase emulsion. A further section was included to provide basic information on the results obtained using each method. This was needed to explain the interacting components derived from pot-honey processing within the stingless bee nest and post-harvest transformations

Interlaboratory Coverage Test on Plant Food Bioactive Compounds and their Metabolites by Mass Spectrometry-Based Untargeted Metabolomics.

Bioactive compounds present in plant-based foods, and their metabolites derived from gut microbiota and endogenous metabolism, represent thousands of chemical structures of potential interest for human nutrition and health. State-of-the-art analytical methodologies, including untargeted metabolomics based on high-resolution mass spectrometry, are required for the profiling of these compounds in complex matrices, including plant food materials and biofluids. The aim of this project was to compare the analytical coverage of untargeted metabolomics methods independently developed and employed in various European platforms. In total, 56 chemical standards representing the most common classes of bioactive compounds spread over a wide chemical space were selected and analyzed by the participating platforms (n = 13) using their preferred untargeted method. The results were used to define analytical criteria for a successful analysis of plant food bioactives. Furthermore, they will serve as a basis for an optimized consensus method

Contribution of plant food bioactives in promoting health effects of plant foods: why look at interindividual variability?

Contribution of plant food bioactives in promoting health effects of plant foods: why look at interindividual variability

Interindividual variation in response to consumption of plant food bioactives and determinants involved (POSITIVe)

To combat the burden of cardiometabolic disease, which constitutes a major public health issue in Europe, it is of crucial importance to develop efficient strategies that target the dietary behaviours of European consumers and improve the food supply. Plant foods are rich sources of a large range of bioactive compounds that beneficially affect our health, particularly by decreasing the risk of cardiometabolic diseases. However, heterogeneity in individuals’ responsiveness to plant food bioactives can obscure associations between dietary intakes and health, hinder the identification of health benefits for specific population groups and limit our understanding of the exact role of the different bioactives. POSITIVe specifically addresses inter-individual variation in bioavailability and physiological responses to consumption of plant food bioactives in relation to cardiometabolic endpoints. This Action will coordinate a multidisciplinary and multisectorial European network, harness and combine the currently fragmented knowledge and ensure the optimal translation of findings into applications. It will promote the leadership of European research in this active and high-profile research field, provide scientific knowledge to regulatory authorities for a new generation of nutritional recommendations targeted to large population subgroups and foster the competitiveness of the European food industry by underpinning the development of new functional/customized foods

Polyphenols: from plants to a variety of food and nonfood uses

Polyphenols are major plant secondary metabolites, structurally extremely diverse, essential for a variety of functions in plants, responsible for major organoleptic and nutritional properties of plant-derived foods, and useful for numerous practical applications. During the 27th International Conference on Polyphenols and 8th Tannin Conference, held jointly in September 2014 in Nagoya, Japan (ICP2014), the latest advances in polyphenol research have been presented. These include advances in polyphenol chemistry, physicochemistry, and materials science; their biosynthesis, genetics, and metabolic engineering; and their role in plant interactions with the environment, in nutrition and health, and in natural medicine. This special issue presents a selection of research papers presented at the meeting, covering these different fields. Major recent progress and perspectives in these areas are also outlined in this introductory paper