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Anthocyanins (ACNs) are promising health-enhancing phenolic compounds. We focus on ACN animal tissue bioavailability to provide an evidentiary link between tissue ACNs and their associated health properties. We performed a systematic review of electronic libraries; 279 results were retrieved, and 13 publications met inclusion criteria. Extracted information included animal model employed, administration route, doses, analysis method, and ACN concentration values in tissues. Total ACN concentrations were detected in mice kidney (2.17 × 105 pmol/g), liver (1.73 × 105 pmol/g), heart (3.6 × 103 pmol/g), and lung (1.16 × 105 pmol/g); and in pig brain (6.08 × 103 pmol/g). ACNs showed a predominance of parent ACNs in long-term experiments versus an ACN metabolite predominance in short-term experiments. ACNs detected in animal tissues, such as cyanidin-3-glucoside, suggest it may have an important role in human health. This information could be useful to determine proper ACN-intake biomarkers in biological samples in futures studies. ; The AppleCOR Project (Subproject AGL2016-76943-C2-2-R and Suproject AGL2016-76943-C2-1-R) has been possible with the support of Ministerio de Economia , Indústria y Competitividad, the Agencia Estatal de Investigación (AEI) and the European Regional Development Fund (ERDF). B.A.S.-R. enjoys a 2017MFP-COFUND-30 predoctoral fellowship contract. This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 713679 and from the Universitat Rovira i Virgili (URV). Ú.C. has a Pla estratègic de recerca i innovació en salut (PERIS) postdoctoral grant (SLT002/16/00239; Catalunya, Spain) from Generalitat de Catalunya; NFOC-Salut group is a consolidated research group of Generalitat de Catalunya, Spain (2017 SGR 522).

Background & aims: The integrity of the intestinal barrier in the diseased is key to prevent further complications and disease such as sepsis and death, whereas, the role of food bioactive molecules (i. e. phenolic compounds (PCs) on the intestinal barrier, is still unknown. The current aim was to explore the benefits of the oral PC administration on the intestinal barrier integrity in animals. Methods: The effects of PCs on the intestinal barrier integrity in in vivo animal models of intestinal inflammation were assessed up-to August 2020 from the PubMed, SCOPUS, and Cochrane Library databases under the PRISMA methodology. The risk of bias was assessed from ARRAY and SCYRCLE tools. Results: From 1241 articles, 14 studies were included. In animals, oral resveratrol (n = 6) improves the intestinal barrier integrity and reduces intestinal damage. Additionally, grape seed extract (n = 2), curcumin (n = 1), genistein (n = 1), chlorogenic acid (n = 1), grape pomace (n = 1), olive leaf (n = 1) or cranberry extract (n = 1) improve the intestinal barrier integrity downregulating various inflammatory molecules (TNF-α, and other interleukins), and increasing the antioxidant enzymes in animals. Furthermore, resveratrol, quercetin, epigallocatechin, and other PCs improve the epithelial barrier integrity and pro-inflammatory molecule expression in the intestinal epithelia. Conclusions: The oral PC administration in animals improves the intestinal barrier integrity and function from three main mechanisms: 1) The reduction of pro-inflammatory molecules, 2) the improvement in tight-junction protein expression, and 3) the improvement of the antioxidant intracellular activity suggesting the potential use of PCs in the management of intestinal injury in humans, particularly for resveratrol, the most studied PC. ; The AppleCOR Project (Subproject AGL2016-76943-C2-2-R and Subproject AGL2016-76943-C2-1-R) has been possible with the support of Ministerio de Economía, Indústria y Competitividad, the Agencia Estatal de Investigación (AEI) and the European Regional Development Fund (ERDF); NFOC-Salut group is a consolidated research group of Generalitat de Catalunya, Spain (2017 SGR 522). S-R. BA. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 713679. This journal article has been possible with the support of the Universitat Rovira i Virgili (URV) and the Fundació Catalunya-La Pedrera (FCLP) (Reference number: 2017MFP-COFUND-30). Ú-C has a Pla estratègic de recerca i innovació en salut (PERIS) post-doctoral grant (SLT002/16/00239; Catalunya, Spain) from Generalitat de Catalunya. M.J. Motilva thanks to Consejo Superior de Investigaciones Científicas-CSIC for partial funding through the "Ayudas incorporación a escalas científicas CSIC, 2018" (Reference 201870I129).

Hydroxytyrosol (HT) is the most prominent phenolic compound of virgin olive oil and due to its scientifically validated biological activities it is entering to the market as a potentially useful supplement for cardiovascular disease prevention. The aim of the present study was to investigate the relationship between the HT dose intake and its tissue uptake in rats, and thus, providing complementary information in relation to the target-dose relationship. Rats were given a refined olive oil enriched with HT at different doses (1, 10, and 100 mg/kg) and they were sacrificed after 5 h to ensure the cell tissue uptake of HT and its metabolites. Plasma samples and different organs as liver, kidney, heart and brain were obtained, and HT metabolites were analyzed by UPLC-MS/MS. The results showed that HT and its metabolites could be accumulated in a dose-dependent manner basically in the liver, kidney, and brain and were detected in these tissues even at nutritionally relevant human doses. The detection of free HT in liver and kidney was noteworthy. To date, this appears to be the only biologically active form, and thus, it provides relevant information for optimizing the potential applications of HT to prevent certain hepatic and renal diseases. In recent years, HT and its derivatives have led to a great interest from the virgin olive oil producers and manufacturers of nutraceutical supplements. The increasing interest in HT is mainly due to the European Food Safety Agency (EFSA) Panel on Dietetic Products, Nutrition, and Allergies (NDA) scientific opinion that established a cause-and-effect relationship between the consumption of olive oil polyphenols and protection of LDL particles from oxidative damage [1]. Based on this positive opinion, the health claim "Olive oil polyphenols contribute to the protection of blood lipids from oxidative stress" was included in the list of health claims [2], being the only authorized health claim in the European Union regarding polyphenols and health. ; This study was supported by the Spanish Ministry of Education and Science (AGL2012-40144-C03-03, AGL2012-40144- C03-02 and AGL2012-40144-C03-01 projects), by the University of Lleida through the M.C. L´opez de las Hazas and L. Rubi´o grant. CIBERobn is an iniciative of Instituto de Salud Carlos III (ISCIII). The authors are grateful for the generous gift of hydroxytyrosol from Seprox Biotech, Madrid, Spain

The aim of this study was to investigate comprehensively the metabolic pathways and human bioavailability of anthocyanins and other phenolic compounds in apple matrix, and to elucidate potential intake biomarkers. After the acute intake of a red-fleshed apple snack, plasma and urine were collected and analyzed by UPLC-MS/MS. A total of 37 phase-II and microbial phenolic metabolites were detected in plasma and urine. Among these, phloretin glucuronide, cyanidin-3-O-galactoside (plasma and urine) and peonidin-3-O galactoside (urine) were the only metabolites detected in all the volunteers and not detected at basal conditions. The maximum urine excretion was detected at 2-4 h, and the main increase in plasma of phloretin glucuronide and cyanidin-3-O-galactoside was observed at 2h post-intake (61.0  6.82 and 10.3  1.50 nM, respectively). These metabolites could be selected as the best intake biomarkers of red-fleshed apple that might be useful in human intervention studies when studying the bioactivity of red-fleshed apple. ; This study was supported by the Spanish Ministry of Industry, Economy and Competitiveness through the AGL2016-76943-C2-1-R and AGL2016-76943-C2- 2-R projects (co-funded by the European Social Fund, European Union); I.A.L. enjoys a post-doctoral contract (2017PMF-POST2-19) from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement and from the Universitat Rovira i Virgili (URV). S.Y. was supported by a grant from the University of Lleida. In addition, the authors are grateful to NUFRI SAT (Mollerussa, Lleida, Catalonia, Spain) for providing the red-fleshed apples. A.P. has Torres Quevedo contract (Subprograma Estatal de Incorporación, Plan Estatal de Investigación Científica y Técnica y de Innovación). NFOC-Salut group is a consolidated research group of Generalitat de Catalunya, Spain (2017 SGR522).

The present study aimed to evaluate the metabolism and bioavailability of anthocyanins (ACN) and other phenolics from red-fleshed apple (RFA) and to define the intake biomarkers compared to common white-fleshed apple (WFA). Acute and sustained (6-week) interventions were combined in a randomized, controlled and parallel study with 121 hypercholesterolemic subjects. Another arm consuming ACN-rich infusion from aronia fruit (ARO) provided matched content and profile of ACN. Plasma, urine and faeces samples were analyzed using UPLC-MS/MS. Results showed higher bioavailability of ACN after ARO compared to RFA, showing a clear apple matrix effect. The dihydrochalcone phloretin-2′-O-glucuronide was the most discriminant intake biomarker of both apples. The urinary peonidin-3-O-galactoside was a good biomarker after both ARO and RFA intakes, whereas peonidin-O-arabinoside was reported to be specific from ARO. The elucidation of the phenolic metabolism and the selection of intake biomarkers is a promising approach to relate phenolic compounds and human health ; This study was supported by the Spanish Ministry of Industry, Economy and Competitiveness through the AGL2016-76943-C2-1-R and AGL2016-76943-C2-2-R projects (co-funded by the European Social Fund, European Union); M.J. Motilva thanks to Consejo Superior de Investigaciones Científicas-CSIC for partial funding throught the "Ayudas incorporación a escalas científicas CSIC, 2018" (Reference 201870I129). L.R. was Sara Borrell postdoctoral contract and she is a Serra Húnter Fellow. I.A.L. enjoys a post-doctoral contract (2017PMF-POST2-19) from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement and from the Universitat Rovira i Virgili (URV). S.Y. was supported by a pre-doctoral grant from the University of Lleida.

Gut microbiota has been suggested to affect lipid metabolism. The objective of this study was to characterize the faecal microbiota signature and both short chain fatty acids (SCFAs) and bile acids (BA) profile of hypercholesterolemic subjects. Microbiota composition, SCFAs, BA and blood lipid profile from male volunteers with hypercholesterolemia (HC) and normocholesterolemia (NC) were determined by 16S rDNA sequencing, HPLC, GC and NMR, respectively. HC subjects were characterized by having lower relative abundance of Anaeroplasma (0.002% vs 0.219%, p-value = 0.026) and Haemophilus (0.041% vs 0.078%, p-value = 0.049), and higher of Odoribacter (0.51% vs 0.16%; p-value = 0.044). Correlation analysis revealed that Anaeroplasma and Haemophilus were associated to an unfavourable lipid profile: they correlated negatively to cholesterol and triglycerides related biomarkers and the ratio total to high density lipoprotein (HDL) cholesterol, and positively to HDL size. Odoribacter displayed an opposite behaviour. Faecal SCFAs profile revealed higher abundance of isobutyric (2.76% vs 0.82%, p-value = 0.049) and isovaleric acid (1.32% vs 0.06%, p-value = 0.016) in HC. Isobutyric acid correlated positively with Odoribacter and lipid parameters indicative of an unfavourable profile. BA profile did not show differences between groups. It was concluded that HC subjects showed a particular faecal bacterial signature and SCFAs profile associated with their lipid profile. ; The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the Seventh Framework Programme of the European Union (FP7/2007-2013) under REA grant agreement No. 600388 (TECNIOspring Progamme) and from the Agency for Business Competitiveness of the Government of Catalonia ACCIÓ that support the fellowship given to Ana Belén Granado-Serrano (TECSPR14-0-0023). I.A.L enjoys a post-doctoral contract (2017PMF-POST2-19) from the European Union's Horizon 2020 research and innovation programme under the Marie ...

The present study aimed to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds (PC) provided by a red‐fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats were feed with high‐fat diet (HFD) to induce hypercholesterolemia and supplemented with red‐fleshed apple (HFD+R), white‐fleshed apple (HFD+W) or an ACN‐rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis and phenol biological metabolites were determined. Plasma, urine and faeces showed a significant increase of ACN metabolites after HFD+R and HFD+A, while flavan‐3‐ols were significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect was observed after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function was improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R and HFD+W) was also observed. Our findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan‐3‐ols, together with dihydrochalcones, compose a phenolic phytocomplex in red and white‐fleshed apples, respectively, that could act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats. ; This study was supported by the Spanish Ministry of Industry, Economy and Competitiveness through the AGL2016-76943-C2-1-R and AGL2016-76943-C2-2-R projects (co-funded by the European Social Fund, European Union). I.A.L. enjoys a post-doctoral contract (2017PMF-POST2-19) from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement and from the Universitat Rovira i Virgili (URV). S.Y. was supported by a grant from the University of Lleida. Ú.C. has a Pla estratègic de recerca i innovació en salut (PERIS) post-doctoral grant (SLT002/16/00239; Catalunya, Spain) from Generalitat de Catalunya. A.P. enjoys a post-doctoral grant (PTQ-15-08068; Spain). In addition, the authors are grateful to NUFRI SAT (Mollerussa, Lleida, Catalonia, Spain) for providing the red-fleshed apples. We are grateful to A. Martínez (Department of Medicine, University of Lleida) for helpful with the histological stains. Finally, we are grateful to SCT-Estabulari of the University of Lleida where the animal experiment was carried out.

Scope:Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels arecharacteristic of cardiovascular disease. Our aim was to assess short- and long-term effects ofvirgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with themplus complementary PC from thyme (FVOOT), on PON-related variables and the mechanismsinvolved.Methods and results:Two randomized, controlled, double-blind, and crossover interventionswere conducted. In an acute intake study, participants ingested three FVOOs differing in PCcontent. In a sustained intake study, participants ingested a control VOO and two differentFVOOs with the same PC content but differing in PC source. Acute and sustained intake ofVOO and FVOO decreased PON1 protein and increased PON1-associated specific activities,while FVOOT yielded opposite results. PON3 protein levels increased only after sustainedconsumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolatedPC from VOO and from thyme modulate mitogen-activated protein kinases and peroxisomeproliferator-activated receptors regulating PON synthesis, while a combination of these PCscancels such regulation.Conclusion:This study reveals that the intake of phenol-enriched FVOOs modulates oxidativebalance by modifying PON-related variables according to PC content and source, and thismodulation can be perceived as beneficial. ; This study was supported by the Spanish Ministry of Econ-omy (MINECO) financing the projects AGL2009-13517-457-C03-01, C03-02 and C03-3, AGL2012-40144-C01-03, C02-03 and C03-03, and the FPI-fellowship (BES-2010-040766), byC©2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheimwww.mnf-journal.com 1600932 (11 of 13)S. Fern ́andez-Castillejo et al.Mol. Nutr. Food Res. 61,10, 2017, 1600932a contract from the Catalan Government, and by grants fromISCIII FEDER (CB06/03/0028), AGAUR(2014SGR240) andAGAUR (2014SGR783). AP is a Torres Quevedo contract (PTQ-15-08068; Subprograma Estatal de Incorporaci ́on, Plan Estatalde Investigaci ́on Cient ́ıfica y T ́ecnica y de Innovaci ́on). UC is aPERIS contract (SLT002/16/00239; Pla estrat`egic de recerca iinnovaci ́o en salut). LR is Sara Borell contract (CD14/00275)co-financed by and IISPV. OC was supported by a research con-tract of Carlos III (SCIII JR14/00008). Thanks to the Universityof Lleida for the M-CLH PhD. grant.