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(1) Background: The fig tree ( Ficus carica L.) is widely cultivated in the Mediterranean area and it produces fruits largely consumed in the Mediterranean diet. Previous studies have shown that this fruit represents a rich source of (poly)phenols, which are mainly located in the peel rather than the pulp. In our study, fig peel derived from twelve different cultivars located in Tuscany was assessed for its (poly)phenol profile. (2) Methods: The (poly)phenol characterization was performed through ultra-high performance liquid chromatography coupled to multiple-stage mass spectrometry. (3) Results: Twenty-eight (poly)phenolic compounds were quantified in the investigated fig peel. It was possible to observe an interesting variability in the (poly)phenol content among the twelve cultivars of fig peel. Rutin and 5-caffeoylquinic acid were the main compounds in the greenish fig peel, while cyanidin-3- O -rutinoside was the main component in the dark-violet fig peel. (4) Conclusions: fig peel could be used as a (poly)phenol-rich ingredient in several food products to increase the bioactive compound content of foods. Moreover, dark-violet peel could be considered potentially suitable as a natural food colorant.

The aim of this work was to address whether the growing location of tomato could generate a different (poly)phenol profile able to affect both in vivo absorption and (poly)phenol metabolite pattern upon tomato consumption. uHPLC-MS n analyses allowed to obtain a detailed (poly)phenol profile of tomatoes from two locations in Spain, quantifying 57 (poly)phenolic compounds. However, local and non-local tomatoes showed a different concentration of their native (poly)phenols, which could be attributed to diverse cultivation origin. Rat serum was analysed after an acute tomato feeding. Seven phenolic metabolites were quantified through uHPLC-MS n . Pharmacokinetic parameters were further evaluated, revealing different serum concentrations of (poly)phenolic metabolites between tomatoes. The maximum peak serum concentrations, reached mainly after 2 h after ingestion, led to suppose that serum metabolites were mostly derived from absorption in the upper gastrointestinal tract. The growing location of tomatoes affected both the content of native (poly)phenols and their in vivo absorption., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Consuming (poly)phenol-rich fruits and vegetables, including tomato, is associated with health benefits. The health effects of tomato (poly)phenolic compounds have been attributed to their metabolites rather than parent compounds and their bioavailability can be modulated by several factors. This study aimed to evaluate the effect of seasonal consumption of local tomatoes on their (poly)phenol bioavailability. For this, (poly)phenol absorption and metabolism were evaluated by ultra-high-performance liquid chromatography coupled with mass spectrometry and linear ion trap mass spectrometric (uHPLC-MS n ) after chronic tomato consumption in Fischer rats exposed to three photoperiods mimicking the seasonal daylight schedule. Tomatoes from two locations in Spain (LT, local tomatoes and NLT, non-local tomatoes) were used in this in vivo feeding study. The bioavailability of tomato (poly)phenols depended on the photoperiod to which the rats were exposed, the metabolite concentrations significantly varying between seasons. In-season tomato consumption allowed obtaining the highest concentration of total circulating metabolites. In addition, the origin of the tomato administered generated marked differences in the metabolic profiles, with higher serum concentrations reached upon NLT ingestion. We concluded that in-season tomato consumption led to an increase in (poly)phenol circulation, whereas LT consumption showed lower circulating metabolites than NLT ones. Thus, the origin of the tomato and the seasonal daylight schedule affect the bioavailability of tomato (poly)phenols, which could also affect their bioactivity.

The health properties related to onion intake are attributed mainly to the presence of bioactive compounds, particularly phenolic and organosulfur compounds (OSCs). The aim of this study was to investigate, for the first time, the effect of an in vitro colonic fermentation on the stability of phenolic and OSCs of fresh and black onion by ultra-high-performance liquid chromatography coupled with mass spectrometry with a linear ion trap (UHPLC-LIT-MS). Throughout colonic fermentation, fresh onion showed an increase in the total phenolic content of 45%, mainly due to an increase in the content of the flavonoid family, while the OSCs remained stable along the fermentation. Black onion presented a different behaviour, showing significant decreases in total (poly)phenol and OSC content, 22 and 48%, respectively. The main compounds found after the in vitro colonic fermentation of fresh onion were isorhamnetin (141 μmol L -1 ), quercetin (95 μmol L -1 ), 3,4-dihydroxybenzoic acid (53 μmol L -1 ), methionine sulfoxide (100 μmol L -1 ) and S -allylcysteine (SAC) (21.7 μmol L -1 ), whereas 3,4-dihydroxybenzoic acid (70 μmol L -1 ), 4-hydroxyphenylacetic acid (68 μmol L -1 ), methionine sulfoxide (82 μmol L -1 ) and S -propylmercapto-L-cysteine (SPMC) (10.1 μmol L -1 ) accounted for the highest concentrations of phenolics and OSCs in fermented black onion. These compounds, presumably present for their absorption and action at the colonic level, could be related to the health benefits of regular consumption of fresh and black onion.

The beneficial properties associated with garlic consumption have been related to the presence of bioactive compounds including (poly)phenols and organosulfur compounds (OSCs). This study aims to assess the effect of in vitro colonic fermentation on fresh and black garlic by determining the transformation of these compounds through ultrahigh-performance liquid chromatography coupled to mass spectrometry with a linear ion trap (uHPLC-LIT-MS). Colonic fermentation had a similar influence on the phenolic content of fresh and black garlic, with total respective decreases of 43.8% and 41.7%. Meanwhile, fermentation resulted in a significant decrease (33%) in OSCs in black garlic. Compounds such as 4-hydroxybenzoic acid, S -allylcysteine (SAC), and methionine sulfoxide were the phenolic compounds and OSCs with the highest concentration in fresh and black garlic after the in vitro fermentation. These compounds, potentially present at the colonic level, might be responsible for the systemic health benefits associated with the consumption of black and fresh garlic.

Background and Aims: Aleurone is the innermost layer of wheat bran, rich in fiber, minerals, vitamins, phenolic compounds, and betaine. The metabolic effects of aleurone rich foods are still unknown. Our aim was to investigate the effects of consuming a Wheat Aleurone rich diet vs. a Refined Wheat diet for 8 weeks on fasting and postprandial glycemic and lipid metabolism, inflammation, and oxidative stress in overweight/obese individuals., Methods and Results: According to a randomized cross-over study design, 23 overweight/obese individuals, age 56 ± 9 years (M±SD), were assigned to two isoenergetic diet - Wheat Aleurone and Refined Wheat diets - for 8 weeks. The diets were similar for macronutrient composition but different for the aleurone content (40-50 g/day in the Wheat Aleurone diet). After each diet, fasting and postprandial plasma metabolic profile, ferulic acid metabolites and 8-isoprostane concentrations in 24-h urine samples were evaluated. Compared with the Refined Wheat Diet, the Wheat Aleurone Diet increased fasting plasma concentrations of betaine by 15% (p = 0.042) and decreased the excretion of 8-isoprostane by 33% (p = 0.035). Conversely, it did not affect the fasting and postprandial glucose, insulin and triglyceride responses, homocysteine, and C-Reactive Protein concentrations, nor excretion of phenolic metabolites., Conclusion: An 8-week Wheat Aleurone Diet improves the oxidative stress and increases plasma betaine levels in overweight/obese individuals with an increased cardiometabolic risk. However, further studies with longer duration and larger sample size are needed to evaluate the benefits of aleurone-rich foods on glucose and lipid metabolism in individuals with more severe metabolic abnormalities., Clinical Trial Registry Number: NCT02150356, (https://clinicaltrials.gov)., Competing Interests: Declaration of competing interest Gabriele Riccardi is member of the Health and Wellbeing Advisory Board of the Barilla company; remuneration for this activity goes to his University Department. All other authors declare no conflict of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Plant biodiversity preservation is one of the most important priorities of today's agriculture. Wheat ( Triticum spp. L.) is widely cultivated worldwide, mostly under a conventional and monovarietal farming method, leading to progressive biodiversity erosion. On the contrary, the evolutionary population (EP) cultivation technique is characterized by mixing and sowing together as many wheat genotypes as possible to allow the crop to genetically adapt over the years in relation to specific pedoclimatic conditions. The objective of this study was to assess the nutritional, chemical and sensory qualities of three different breads obtained using different organic EP flours, produced following a traditional sourdough process and compared to a commercial wheat cultivar bread. Technological parameters, B-complex vitamins, microelements, dietary fibre and phenolic acids were determined in raw materials and final products. Flours obtained by EPs showed similar characteristics to the commercial wheat cultivar flour. However, significant differences on grain technological quality were found. The breads were comparable with respect to chemical and nutritional qualities. Overall, the sensory panellists rated the tasted breads positively assigning the highest score to those produced with EPs flours (6.75-7.02) as compared to commercial wheat cultivar-produced bread (cv. Bologna, 6.36).

Okara is the main soybean by-product resulting from the processing of soy milk and tofu. Despite being a product with a lot of potential and rich in many bioactive compounds such as polyphenols, it presents an unpleasant, rancid aroma. For this reason its use in the food industry is limited. In this study, we have reported the integral use of okara in a solid state fermentation process, conducted with wild strains of lactic acid bacteria, to evaluate the effect of bacterial metabolism on the volatile and polyphenolic profiles. Strains belonging to Lactobacillus acidophilus, Lacticaseibacillus rhamnosus and Pediococcus acidilactici species were used in monoculture and, for the first time, in co-culture. The results showed an improvement in the aromatic fraction showing a decrease in hexanal, responsible for off-flavour, and an increase in ketones with fruity and buttery notes in fermented okara. Polyphenols were also affected, and, in particular, a bioconversion of glucoside isoflavones to the aglycone forms was highlighted in all fermented substrates. In addition, the appearance of both phenyllactic and p-hydroxyphenyllactic acids as well as the increase in indole-3-lactic acid was observed for the first time upon okara fermentation. Overall, the co-culture appears to be the most promising for biovalorization of okara, thereby opening the possibility of its use in the development of functional ingredients.

Cranberries (Vaccinium macrocarpon) represent an important source of anthocyanins, flavan-3-ols and flavonols. This study aimed at investigating in vitro the human microbial metabolism of (poly)phenols, principally flavan-3-ols, of unformulated- and phytosome-formulated cranberry extracts. After powder characterization, a 24-h fermentation with human faecal slurries was performed, standardizing the concentration of incubated proanthocyanidins. Cranberry (poly)phenol metabolites were quantified by uHPLC-MS 2 analyses. The native compounds of both unformulated- and phytosome-formulated cranberry extracts were metabolized under faecal microbiota activity, resulting in twenty-four microbial metabolites. Although some differences appeared when considering different classes of colonic metabolites, no significant differences in the total amount of metabolites were established after 24 h of incubation period. These results suggested that a different formulation had no effect on flavan-3-ol colonic metabolism of cranberry and both unformulated- and phytosome-formulated extract. Both formulations displayed the capability to be a potential source of compounds which could lead to a wide array of gut microbiota metabolites in vitro., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Quercetin is one of the main dietary flavonols, but its beneficial properties in disease prevention may be limited due to its scarce bioavailability. For this purpose, delivery systems have been designed to enhance both stability and bioavailability of bioactive compounds. This study aimed at investigating the human microbial metabolism of quercetin derived from unformulated and phytosome-formulated quercetin through an in vitro model. Both ingredients were firstly characterized for their profile in native (poly)phenols, and then fermented with human fecal microbiota for 24 h. Quantification of microbial metabolites was performed by ultra-high performance liquid chromatography coupled to mass spectrometry (uHPLC-MS n ) analyses. Native quercetin, the main compound in both products, appeared less prone to microbial degradation in the phytosome-formulated version compared to the unformulated one during fecal incubation. Quercetin of both products was bioaccessible to colonic microbiota, resulting in the production of phenylpropanoic acid, phenylacetic acid and benzoic acid derivatives. The extent of the microbial metabolism of quercetin was higher in the unformulated ingredient, in a time-dependent manner. This study opened new perspectives to investigate the role of delivery systems on influencing the microbial metabolism of flavonols in the colonic environment, a pivotal step in the presumed bioactivity associated to their intake.

It is widely recognized that the biological effects of phytochemicals cannot be attributed to the native compounds present in foods but rather to their metabolites endogenously released after intake. Bioavailability depends on bioaccessibility, which is the amount of the food constituent that is released from the matrix in the gastrointestinal tract. The use of chemical extraction to evaluate the content and profile of phytochemicals does not mirror the physiological situation in vivo, and their bioaccessibility should be considered while assessing their nutritional significance in human health. The current study was designed to compare the (poly)phenolic profile and content and antioxidant capacity of whole-grain (WG) cookies using chemical extraction and a more physiological approach based on simulated digestion. Three types of organic WG cookies (made with durum, Italian khorasan, or KAMUT ® khorasan wheat) were considered, either fermented by Saccharomyces Cerevisiae or sourdough. Although the flour type and the fermentation process influenced the release of phytochemicals from the cookie matrix, in almost all samples, the simulated digestion appeared the most efficient procedure. Our results indicate that the use of chemical extraction for evaluation of the phytochemicals content and antioxidant capacity of food could lead to underestimation and underline the need for more physiological extraction methods.

Wheat (Triticum spp. L.) is an important source of nutrients and bioactive compounds with recognized beneficial effects. Wheat undergoes several processes with the final aim of separating the endosperm from the outer layers, usually discarded. In this study, free and bound phenolic acids (PAs) profile, betaine and choline contents were quantified in six different wheat species (durum and bread wheat, turanicum wheat, einkorn, emmer and spelt), the corresponding milling by-products (bran, middlings, aleurone and I, II and III steps of debranning) and flour/semolina, using UHPLC-MS/MS methods. The bound form of phenolics was the component present in higher concentration (80% of the total, in average) and ferulic acid was the most abundant compounds, representing between 67 and 73 % of total PAs. Among the species, bread wheat grain totalized the highest content of total PAs (1209.31 ± 7.3 µg g -1 d.w.). Betaine and choline are abundantly present in wheat species. In general, the highest content of bioactive compounds was found in bran (3 times higher than whole grains), emphasizing the good nutritional profile of these by-products. The milling process leads to a severe reduction of phenolic acids and methyl-donors in the end-products., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Turmeric ( Curcuma longa L.) is the only edible plant recognized as a dietary source of curcuminoids, among which curcumin, demethoxycurcumin (DMC) and bis-demethoxycurcumin (Bis-DMC) are the most representative ones. Curcumin shows a very low systemic bioavailability and for this reason, several technologies have been adopted to improve it. These technologies generally improve curcuminoid absorption in the small intestine, however, no data are available about the effect of curcuminoid formulation on colonic biotransformation. The present study aims at investigating the human colonic metabolism of curcuminoids, prepared with two different technologies, using an in vitro model. Unformulated curcuminoid and lecithin-curcuminoid botanical extracts were fermented using an in vitro fecal model and colonic catabolites were identified and quantified by uHPLC-MS n . Native compounds, mainly curcumin, DMC and bis-DMC, were metabolized by colonic microbiota within the 24-h incubation. The degradation of curcuminoids led to the formation of specific curcuminoid metabolites, among which higher concentrations of bis(demethyl)-tetrahydrocurcumin and bis(demethyl)-hexahydrocurcumin were found after lecithin-extract fermentation compared to the concentration detected after unformulated extract. In conclusion, both curcumin-based botanical extracts can be considered important sources of curcuminoids, although the lecithin-formulated extract led to a higher production of curcuminoid catabolites. Moreover, a new curcuminoid catabolite, namely bis(demethyl)-hexahydrocurcumin, has been putatively identified, opening new perspectives in the investigation of curcuminoid bioavailability and their potential metabolite bioactivity.

Purpose: There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated., Methods: Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites., Results: (Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids., Conclusions: The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet.

Covering: 1958 to June 2018 Phenyl-γ-valerolactones (PVLs) and their related phenylvaleric acids (PVAs) are the main metabolites of flavan-3-ols, the major class of flavonoids in the human diet. Despite their presumed importance, these gut microbiota-derived compounds have, to date, in terms of biological activity, been considered subordinate to their parent dietary compounds, the flavan-3-ol monomers and proanthocyanidins. In this review, the role and prospects of PVLs and PVAs as key metabolites in the understanding of the health features of flavan-3-ols have been critically assessed. Among the topics covered, are proposals for a standardised nomenclature for PVLs and PVAs. The formation, bioavailability and pharmacokinetics of PVLs and PVAs from different types of flavan-3-ols are discussed, taking into account in vitro and animal studies, as well as inter-individual differences and the existence of putative flavan-3-ol metabotypes. Synthetic strategies used for the preparation of PVLs are considered and the methodologies for their identification and quantification assessed. Metabolomic approaches unravelling the role of PVLs and PVAs as biomarkers of intake are also described. Finally, the biological activity of these microbial catabolites in different experimental models is summarised. Knowledge gaps and future research are considered in this key area of dietary (poly)phenol research.

Pistachio hull is a substantial source of natural polyphenols, but a substantial volume is being wasted annually. Aqueous pistachio green hull extract (PGHE) was subjected to two-stage membrane process in order to separate a polyphenol rich fraction. The membrane conditions of each stage were investigated. Total phenolic content and antioxidant activity were determined by Folin-Ciocalteu and DPPH · assay; also membrane fouling was monitored. The use of the 1 kDa cellulose membrane accompanied by 4 bar pressure and 250 rpm stirring speed was observed to be successful in the separation of a fraction with the highest amount of phenolic compound and antioxidant activity, in the retentate part. UHPLC/MS n characterization of PGHE polyphenols enabled us to identify 34 compounds, including the most abundant galloylshikimic acids, gallic acid, theogallin, galloyl-O-hexoside, quercetin-O-hexoside and pyrogallol., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study, ten strains of Lactobacillus were used to assess the in vitro metabolism of elderberry juice polyphenols. Total polyphenolic compounds increased after starter addition, especially with three L. rhamnosus and one L. plantarum strains, of dairy origin: quercetin-3-O-rutinoside was the most abundant compound (from 39.02 ± 5.28 to 127.56 ± 11.34 µg/mL) and hydroxycinnamic acids, flavonols and anthocyanins reached the highest amounts. When L. plantarum were used phenyllactic acids presented a value of 7.05 ± 2.38 µg/mL, while in the other samples it was around 5.56 ± 1.65 µg/mL. Hydroxycinnamic and hydroxybenzoic acids were subjected to lactic acid bacteria metabolism: caffeic and protocatechuic acids were consumed during fermentation while dihydrocaffeic acid and catechol were produced. Anthocyanins increased in a strain-specific way. So, by this study we highlighted that dairy strains can produced (phenyllactic acids), modified (hydroxycinnamic acids) or increased (flavonols glycosides and anthocyanins) phenolic compounds., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Lactic acid bacteria (LAB) exhibit a great biodiversity that can be exploited for different purposes, such as to enhance flavours or metabolize phenolic compounds. In the present study, the use of dairy and plant-derived LAB strains to perform cherry juice fermentation is reported., Methods: The growth ability of Lactobacillus plantarum , Lactobacillus casei , Lactobacillus paracasei and Lactobacillus rhamnosus was studied in cherry juice. Profiling of sugars, organic acids and volatile compounds was performed by GC-MS (Gas Chromatography-Mass Spectrometry), while the phenolic fraction was characterized using UHPLC (Ultra High Performance Liquid Chromatography) equipped with a linear ion trap-mass spectrometer., Results: Sucrose significantly decreased in all fermented samples as well as malic acid, converted to lactic acid by malolactic fermentation. The total amount of volatile compounds increased. Specifically, propyl acetate, an ester with fruit notes, reached the highest concentration in L. rhamnosus and L. paracasei (dairy strains) fermented juices. Phenolics were extensively metabolized: caffeic acid was converted into dihydrocaffeic acid, p -coumaric acid into 4-ethylphenol and phenyllactic acid was produced., Conclusion: Lactic acid fermentation confer fruit notes to the juice and enhance phenyllactic acids, especially employing dairy strains ( L. rhamnosus and L. paracasei ). The level of dihydrocaffeic acid, a compound with putative biological activity was also increased (in particular with L. plantarum ).

Trimethylamine-N-oxide (TMAO) has been described as a new biomarker of cardiovascular disease (CVD), derived from gut microbial biotransformation of dietary choline and l-carnitine into trimethylamine (TMA) and subsequent hepatic oxidation. (Poly)phenols are among the dietary factors able to interfere with microbial enzymatic activity, possibly modulating TMA biotransformation at the gut level. The aim of this work was to investigate the in vitro biotransformation of choline and carnitine using faecal starters obtained from omnivorous and vegetarian subjects and the effect of (poly)phenol-rich foods on TMA production. Choline and l-carnitine were fermented with vegetarian or omnivorous faecal slurries, alone or in combination with 10 (poly)phenol-rich food items. TMA production from carnitine, but not from choline, was significantly lower when vegetarian faecal starters were used and, among the tested food items, blonde orange juice significantly reduced TMA formation during faecal biotransformation. Consequently, the main compounds of orange juice, namely phenolic compounds, terpenes, limonoids, organic acids and sugars, were tested individually. Sugars exerted the highest inhibitory effect on TMA production. Despite some limitations deriving from the applied in vitro model, this is the first work describing a possible role of some (poly)phenol-rich dietary products on the modulation of TMA colonic production. Free sugars were the main factor responsible for TMA inhibition, suggesting a potential beneficial role of colonic fermentation of carbohydrates in reducing TMA formation from its precursor molecules. This work opens new research directions to evaluate the effect of dietary fermentable fibre on TMA production and, potentially, on circulating TMAO levels.

In this study, four strains of Lactobacillus casei , as viable cells or cell-free extracts (CFE), were added to elderberry juice in order to evaluate their effect on phenolic and aromatic profile. Two of them were able to grow in juice while the others showed zero-growth. The same strains were lysed and added as extracts in elderberry juice. Multivariate statistical analysis show a separation among samples containing growing cells, non-growing cells, CFE, highlighting the particularities of specific strains. Juices added with CFE presented the highest amount of esters. The strains showing growth phenotype cause an increase of phenyllactic acids. The highest concentration of volatile compounds, particularly of alcohols, terpenes and norisoprenoids (responsible for typical elderberry notes) was observed in samples with strains showing zero-growth. Moreover, a significant increase in anthocyanin content was observed in these samples, suggesting the possible use of Lactobacillus for increasing specific molecules, even for non-multiplying bacterial cell. Considering that this is the first study concerning the use of non-growing cells in fruit juice, the potential of strains is still to be explored and it may have a significant technological application in the development of a microbial collection useful for fruit juice industry.

Preclinical studies have suggested that polyphenols extracted from red wine (RWPs) favourably affect insulin sensitivity, but there is controversy over whether RWPs exert similar effects in humans. The aim of the present study was to determine whether RWPs improve insulin sensitivity in obese volunteers. Obese (body mass index >30 kg/m 2 ) volunteers were randomly allocated to RWPs 600 mg/d (n = 14) or matched placebo (n = 15) in a double-blind parallel-arm study for 8 weeks. The participants were investigated at baseline and at the end of the study. Insulin sensitivity was determined using a hyperinsulinaemic-euglycaemic clamp (M-value), a mixed-meal test (Matsuda index), and homeostatic model assessment of insulin resistance (HOMA-IR). RWPs elicited no significant changes in M-value (RWP group: median [interquartile range; IQR] baseline 3.0 [2.4; 3.6]; end of study 3.3 [2.4; 4.8] vs placebo group: median [IQR] baseline 3.4 [2.8; 4.4]; end of study 2.9 [2.8; 5.9] mg/kg/min; P = .65), in Matsuda index (RWP group: median [IQR] baseline 3.3 [2.2; 4.8]; end of study 3.6 [2.4; 4.8] vs placebo group: median [IQR] baseline 4.0 [3.0; 6.0]; end of study 4.0 [3.0; 5.2]; P = .88), or in HOMA-IR. This study showed that 8 weeks of RWP supplementation did not improve insulin sensitivity in 29 obese volunteers. Our findings were not consistent with the hypothesis that RWPs ameliorate insulin resistance in human obesity., (© 2017 John Wiley & Sons Ltd.)

Scope: The contribution of the gut microbiota to the metabolism of catechins and proanthocyanidins remains unclear. Phenyl-γ-valerolactones have been identified as the most representative metabolites of these dietary flavan-3-ols, but their accurate quantification has posed problems because of a lack of appropriate bioanalytical standards. This work aimed at synthesizing a novel set of sulphate- and glucuronide-conjugated phenyl-γ-valerolactones and at developing an analytical platform using UHPLC-ESI-MS/MS for their quantification in urine., Methods and Results: Eight glucuronide and sulphate conjugates of hydroxyphenyl-γ-valerolactones were synthesized and used as analytical standards, together with five phenyl-γ-valerolactone aglycones, for the development of a high-throughput, validated analytical method. Chromatographic and MS conditions were optimized. The method validation showed acceptable linearity, intra-day and inter-day repeatability, and accuracy, with the analytical range, limit of detection (LOD), and lower limit of quantification (LLOQ) varying notably among compounds. The method was used to calculate the excretion of phenyl-γ-valerolactones in healthy subject consuming green tea, providing novel information on the real concentrations of phenyl-γ-valerolactones in urine., Conclusion: This work opens the door to better studying the bioavailability of flavan-3-ols and the real exposition to flavan-3-ol sources, as well as to define the bioactivity of these colonic metabolites in cell assays., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The market of plant-based nutraceuticals and food supplements is continuously growing due to the increased consumer demand. The introduction of new products with relevant nutritional characteristics represents a new way of providing bioactive compounds and (poly)phenols to consumers, becoming a strategy to ideally guarantee the health benefits attributed to plant foodstuffs and allowing the increase of daily bioactive compound intake. A paramount step in the study of nutraceuticals is the evaluation of the bioavailability and metabolism of their putatively active components. Therefore, the aim of the present study was to investigate the absorption profile of the (poly)phenolic compounds contained in three different plant-based food supplements, made of 36 different plant matrices, which were consumed by 20 subjects in an open one-arm study design. Blood samples were collected at baseline and 1, 2, 5, and 10 h after capsule intake. Twenty quantifiable metabolites deriving from different (poly)phenolic compounds were identified. Results showed that the consumption of the three capsules allowed the effective absorption of several (poly)phenolic compounds and metabolites appearing at different times in plasma, thereby indicating different absorption profiles. The capsules thus ensured potential health-promoting molecules to be potentially available to target tissues and organs.

Purpose: Urolithins are bioactive ellagitannin-derived metabolites showing a wide phenotypic variation in their production by the gut microbiota. This work represents a first in vitro step toward the development of new strategies focused on the oral supplementation of urolithins with the aim of overcoming their selective production and making their putative health benefits available for the whole population., Methods: In order to study their gastrointestinal stability, urolithin A, urolithin B, and urolithin B-glucuronide, as well as ellagic acid, were subjected to a simulated gastrointestinal digestion model consisting of oral, gastric, and pancreatic steps followed by a 24-h fecal fermentation. The effect of the entero-hepatic recirculation on urolithin B-glucuronide, a phase II metabolite, was also investigated., Results: Urolithin B was the molecule able to resist to a greater extent the conditions of the gastrointestinal tract, while urolithin A and ellagic acid were drastically unstable during the colonic step. Conjugation with glucuronic acid, ideally occurring in the liver, conferred to urolithin B an increased stability, which may be interesting in the framework of entero-hepatic recirculation., Conclusion: This set of experiments lets hypothesize that orally supplemented urolithins may come into contact with the colonic epithelium and become accessible for uptake or exert local anti-inflammatory activity, overcoming the limitations of enterotypes unable to convert ellagitannins into these putatively beneficial metabolites.

As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers' health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats. The intake of plant n-3 alpha-linolenic acid and WR results in a sort of fatty fish-like effect, demonstrating that the n-3 LCFA levels in blood and tissues could be increased without eating marine foods, and therefore without promoting unsustainable overfishing, and without damaging marine ecology.

Background: Whole rye (WR) consumption seems to be associated with beneficial health effects. Although rye fiber and polyphenols are thought to be bioactive, the mechanisms behind the health effects of WR have yet to be fully identified. This study in rats was designed to investigate whether WR can influence the metabolism of n-3 and n-6 long-chain fatty acids (LCFA) and gut microbiota composition., Methods: For 12 weeks, rats were fed a diet containing either 50% WR or 50% refined rye (RR). The WR diet provided more fiber (+21%) and polyphenols (+29%) than the RR diet. Fat intake was the same in both diets and particularly involved similar amounts of essential (18-carbon) n-3 and n-6 LCFAs., Results: The WR diet significantly increased the 24-hour urinary excretion of polyphenol metabolites-including enterolactone-compared with the RR diet. The WR rats had significantly more n-3 LCFA-in particular, eicosapentanoic (EPA) and docosahexanoic (DHA) acids-in their plasma and liver. Compared with the RR diet, the WR diet brought significant changes in gut microbiota composition, with increased diversity in the feces (Shannon and Simpson indices), decreased Firmicutes/Bacteroidetes ratio and decreased proportions of uncultured Clostridiales cluster IA and Clostridium cluster IV in the feces. In contrast, no difference was found between groups with regards to cecum microbiota. The WR rats had lower concentrations of total short-chain fatty acids (SCFA) in cecum and feces (p<0.05). Finally, acetate was lower (p<0.001) in the cecum of WR rats while butyrate was lower (p<0.05) in the feces of WR rats., Interpretation: This study shows for the first time that WR consumption results in major biological modifications-increased plasma and liver n-3 EPA and DHA levels and improved gut microbiota profile, notably with increased diversity-known to provide health benefits. Unexpectedly, WR decreased SCFA levels in both cecum and feces. More studies are needed to understand the interactions between whole rye (fiber and polyphenols) and gut microbiota and also the mechanisms of action responsible for stimulating n-3 fatty acid metabolism.

Wheat aleurone, due to its potentially higher bioaccessibility and bioavailability of micronutrients and phenolic acids, could represent a useful ingredient in the production of commonly consumed cereal-based food. The aim of the present study was to investigate the in vitro bioaccessibility of phenolic acids both from an aleurone-enriched bread and from a whole grain bread. The two bread samples were firstly characterized for the phenolic acid content. An in vitro digestion was then performed in order to evaluate the release of phenolic acids. The results obtained suggest that the bioaccessibility of the phenolic acids in the aleurone-enriched bread is higher than in the whole grain bread. These in vitro results suggest the potential use of aleurone in the production of foods, and this may represent an attractive possibility to vehicle nutritionally interesting components to consumers.

Red raspberries, containing ellagitannins and cyanidin-based anthocyanins, were fed to volunteers and metabolites appearing in plasma and urine were analysed by UHPLC-MS. Anthocyanins were not absorbed to any extent with sub nmol/L concentrations of cyanidin-3-O-glucoside and a cyanidin-O-glucuronide appearing transiently in plasma. Anthocyanins excreted in urine corresponded to 0.007% of intake. More substantial amounts of phase II metabolites of ferulic acid and isoferulic acid, along with 4'-hydroxyhippuric acid, potentially originating from pH-mediated degradation of cyanidin in the proximal gastrointestinal tract, appeared in urine and also plasma where peak concentrations were attained 1-1.5h after raspberry intake. Excretion of 18 anthocyanin-derived metabolites corresponded to 15.0% of intake, a figure substantially higher than obtained in other anthocyanin feeding studies. Ellagitannins pass from the small to the large intestine where the colonic microbiota mediate their conversion to urolithins A and B which appeared in plasma and were excreted almost exclusively as sulfate and glucuronide metabolites. The urolithin metabolites persisted in the circulatory system and were excreted in urine for much longer periods of time than the anthocyanin metabolites although their overall urinary recovery was lower at 7.0% of intake. It is events originating in the proximal and distal gastrointestinal tract, and subsequent phase II metabolism, that play an important role in the bioavailability of both anthocyanins and ellagitannins and it is their metabolites which appear in the circulatory system, that are key to elucidating the mode of action(s) underlying the protective effects of these compounds on human health., (Copyright © 2015 Elsevier Inc. All rights reserved.)