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Papers by Anna Pedret

Nutrients, 2022

The impact of a red-fleshed apple (RFA) rich in anthocyanins (ACNs), a white-fleshed apple (WFA) ... more The impact of a red-fleshed apple (RFA) rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an extract infusion from Aronia fruit (AI) equivalent in dose of cyanidin-3-O-galactoside (main ACN) as RFA was determined by the proteome profile of aorta and heart as key cardiovascular tissues. Hypercholesterolaemic Wistar rats were separated into six groups (n = 6/group; three males and three females) and the proteomic profiles were analyzed using nanoliquid chromatography coupled to mass spectrometry. No adverse events were reported and all products were well tolerated. RFA downregulated C1QB and CFP in aorta and CRP in heart. WFA downregulated C1QB and CFP in aorta and C9 and C3 in aorta and heart, among other proteins. AI downregulated PRKACA, IQGAP1, and HSP90AB1 related to cellular signaling. Thus, both apples showed an anti-inflammatory effect through the complement system, while RFA reduced CRP. Regardless of the ACN content, an apple matrix effect was observ...

Molecular Nutrition & Food Research, 2021

Scope: The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new b... more Scope: The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function. Methods and results: A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity. Conclusion: VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function.

Molecular Nutrition & Food Research, 2021

The present study aimed to investigate the metabolic fate and the cardiometabolic effects of phen... more 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 highfat diet (HFD) to induce hypercholesterolemia and supplemented with redfleshed 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 but only in females, probably related to the higher phenol bioavailability reported in females. A decrease in insulin plasma concentration after both apples supplementation was also observed only in males. Our findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3ols, 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.

Journal of Functional Foods, 2021

In a randomized, parallel, double-blind, placebo-controlled trial, participants with elevated blo... more In a randomized, parallel, double-blind, placebo-controlled trial, participants with elevated blood pressure and stage 1 hypertension (n = 159) received 500 mL/day of control drink, orange juice (OJ), or hesperidin-enriched OJ (EOJ) for 12-weeks, and their ischaemic reactive hyperemia (IRH) was assessed at baseline and after 4, 8, and 12-weeks. Two dose-response studies were nested within the sustained-consumption study: at baseline and after 12-weeks, a single dose of 500 mL was administered. All treatments increased postpandrial IRH, and a higher increase was obtained with EOJ. Moreover, hs-CRP and IL6 increased but not after EOJ. After 12 weeks of sustained consumption: IRH values after EOJ increased versus control group; EOJ treatment increased DSP and decreased IEX-1 gene expression in PBMCs; and IRH directly correlated to NO and inversely to MPO and IEX1. Thus, hesperidin in OJ improves human endothelial function, lower inflammatory status at systemic level and changes at transcriptomic level might account for the increased IRH observed.

Scientific Reports, 2020

Hypertension is an independent and preventable risk factor for the development of cardiovascular ... more Hypertension is an independent and preventable risk factor for the development of cardiovascular diseases, however, little is known about the impact of gut microbiota composition in its development. We carried out comprehensive gut microbiota analysis and targeted metabolomics in a cross-sectional study of 29 non-treated hypertensive (HT) and 32 normotensive (NT) subjects. We determined fecal microbiota composition by 16S rRNA gene sequencing and bacterial functions by metagenomic analysis. The microbial metabolites analysed were short chain fatty acids (SCFA) both in plasma and feces, and trimethylamine N-oxide (TMAO) in plasma. The overall bacterial composition and diversity of bacterial community in the two groups were not significantly different. However, Ruminococcaceae NK4A214, Ruminococcaceae_UCG-010, Christensenellaceae_R-7, Faecalibacterium prausnitzii and Roseburia hominis were found to be significantly enriched in NT group, whereas, Bacteroides coprocola, Bacteroides pleb...

Nutrients, 2021

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to... more We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposit...

Food & Function, 2020

This work fills a gap in the understanding of the effect of processing on the bioavailability of ... more This work fills a gap in the understanding of the effect of processing on the bioavailability of (poly)phenols in fruit products.

Molecular Nutrition & Food Research, 2020

European Journal of Nutrition, 2020

Purpose To assess the sustained and acute effects, as well as the influence of sustained consumpt... more Purpose To assess the sustained and acute effects, as well as the influence of sustained consumption on the acute effects, of orange juice (OJ) with a natural hesperidin content and hesperidin-enriched OJ (EOJ) on blood (BP) and pulse (PP) pressures in pre- and stage-1 hypertensive individuals. Methods In a randomized, parallel, double-blind, placebo-controlled trial, participants (n = 159) received 500 mL/day of control drink, OJ, or EOJ for 12 weeks. Two dose–response studies were performed at baseline and after 12 weeks. Results A single EOJ dose (500 mL) reduced systolic BP (SBP) and PP, with greater changes after sustained treatment where a decrease in diastolic BP (DBP) also occurred (P < 0.05). SBP and PP decreased in a dose-dependent manner relative to the hesperidin content of the beverages throughout the 12 weeks (P < 0.05). OJ and EOJ decreased homocysteine levels at 12 weeks versus the control drink (P < 0.05). After 12 weeks of EOJ consumption, four genes relat...

Clinical Nutrition, 2020

Background & aims: The integrity of the intestinal barrier in the diseased is key to prevent furt... more 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 ¼ 6) improves the intestinal barrier integrity and reduces intestinal damage. Additionally, grape seed extract (n ¼ 2), curcumin (n ¼ 1), genistein (n ¼ 1), chlorogenic acid (n ¼ 1), grape pomace (n ¼ 1), olive leaf (n ¼ 1) or cranberry extract (n ¼ 1) improve the intestinal barrier integrity downregulating various inflammatory molecules (TNF-a, 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.

Molecular Nutrition & Food Research, 2018

Journal of Functional Foods, 2019

The aim of this study was to investigate comprehensively the metabolic 27 pathways and human bioa... more The aim of this study was to investigate comprehensively the metabolic 27 pathways and human bioavailability of anthocyanins and other phenolic 28 compounds in apple matrix, and to elucidate potential intake biomarkers. After 29 the acute intake of a red-fleshed apple snack, plasma and urine were collected 30 and analyzed by UPLC-MS/MS. A total of 37 phase-II and microbial phenolic 31 metabolites were detected in plasma and urine. Among these, phloretin 32 glucuronide, cyanidin-3-O-galactoside (plasma and urine) and peonidin-3-O-33 galactoside (urine) were the only metabolites detected in all the volunteers and 34 not detected at basal conditions. The maximum urine excretion was detected at 35 2-4 h, and the main increase in plasma of phloretin glucuronide and cyanidin-3-36 O-galactoside was observed at 2h post-intake (61.0  6.82 and 10.3  1.50 nM, 37 respectively). These metabolites could be selected as the best intake 38 biomarkers of red-fleshed apple that might be useful in human intervention 39 studies when studying the bioactivity of red-fleshed apple.

Molecular nutrition & food research, Aug 29, 2018

The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF) study and othe... more The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF) study and other related studies on the effect of phenol-enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work. VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double-blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80 mg/kg), FVOO (500 mg/kg), and FVOOT (500 mg/kg;1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat-soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing faecal microbial metabolic activity. Additional cardioprotective bene...

The Journal of nutritional biochemistry, 2018

At present, high-density lipoprotein (HDL) function is thought to be more relevant than HDL chole... more At present, high-density lipoprotein (HDL) function is thought to be more relevant than HDL cholesterol quantity. Consumption of olive oil phenolic compounds (PCs) has beneficial effects on HDL-related markers. Enriched food with complementary antioxidants could be a suitable option to obtain additional protective effects. Our aim was to ascertain whether virgin olive oils (VOOs) enriched with (a) their own PC (FVOO) and (b) their own PC plus complementary ones from thyme (FVOOT) could improve HDL status and function. Thirty-three hypercholesterolemic individuals ingested (25 ml/day, 3 weeks) (a) VOO (80 ppm), (b) FVOO (500 ppm) and (c) FVOOT (500 ppm) in a randomized, double-blind, controlled, crossover trial. A rise in HDL antioxidant compounds was observed after both functional olive oil interventions. Nevertheless, α-tocopherol, the main HDL antioxidant, was only augmented after FVOOT versus its baseline. In conclusion, long-term consumption of phenol-enriched olive oils induced...

Molecular nutrition & food research, Oct 25, 2017

Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic o... more Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic of cardiovascular disease. Our aim was to assess short- and long-term effects of virgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with them plus complementary PC from thyme (FVOOT), on PON-related variables and the mechanisms involved. Two randomized, controlled, double-blind, and crossover interventions were conducted. In an acute intake study, participants ingested three FVOOs differing in PC content. In a sustained intake study, participants ingested a control VOO and two different FVOOs with the same PC content but differing in PC source. Acute and sustained intake of VOO and FVOO decreased PON1 protein and increased PON1-associated specific activities, while FVOOT yielded opposite results. PON3 protein levels increased only after sustained consumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolated PC from VOO and fr...

Molecular nutrition & food research, Dec 8, 2017

Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL co... more Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL composition, fluidity, oxidation, and size are related with CEC. We aimed to assess which HDL parameters were CEC determinants after virgin olive oil (VOO) ingestion. Post-hoc analyses from the VOHF study, a crossover intervention with three types of VOO. We assessed the relationship of 3-week changes in HDL-related variables after intervention periods with independence of the type of VOO. After univariate analyses, mixed linear models were fitted with variables related with CEC and fluidity. Fluidity and Apolipoprotein (Apo)A-I content in HDL was directly associated, and HDL oxidative status inversely, with CEC. A reduction in free cholesterol, an increase in triglycerides in HDL, and a decrease in small HDL particle number or an increase in HDL mean size, were associated to HDL fluidity. HDL fluidity, ApoA-I concentration, and oxidative status are major determinants for CEC after VOO. Th...

Molecular nutrition & food research, Oct 29, 2016

Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in both free and com... more Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in both free and complex forms (secoiridoids; SEC). Proteomics of cardiovascular tissues such as aorta or heart represents a promising tool to uncover the mechanisms of action of phenolic compounds in healthy animals. Twelve female Wistar rats were separated into three groups: a standard diet and two diets supplemented in phenolic compounds (HT and SEC) adjusted to 5 mg/kg/day during 21 days. Proteomic analyses of aorta and heart tissues were performed by nano-liquid chromatography and mass spectrometry. Ingenuity Pathway Analysis was used to generate interaction networks. HT or SEC modulated aorta and heart proteome compared to the standard diet. The top-scored networks were related to Cardiovascular System. HT and SEC downregulated proteins related to proliferation and migration of endothelial cells and occlusion of blood vessels in aorta and proteins related to heart failure in heart tissue. SEC showed h...

Journal of Agricultural and Food Chemistry, 2016

The effect of virgin olive oil (VOO) enriched with its own polyphenols (PC) and/or thymephenols o... more The effect of virgin olive oil (VOO) enriched with its own polyphenols (PC) and/or thymephenols on the protection of oxidative DNA damage and antioxidant endogenous enzymatic system (AEES) were estimated in 33 hyperlipidemic subjects after the consumption of VOO, VOO enriched with its own PC (FVOO), or complemented with thyme PC (FVOOT). Compared to pre-intervention, 8-hydroxy-2'-deoxyguanosine (marker for DNA damage) decreased in the FVOO intervention and to a greater extent in the FVOOT with a parallel significant increase in olive and thyme phenolic biomarkers. Superoxide Dismutase (AEES enzyme) significantly increased in the FVOO intervention and to a greater extent in the FVOOT with a parallel significant increase in thyme phenolic metabolites. When comparing all three oils, FVOOT appeared to have the greatest effect in protecting against oxidative DNA damage and improving AEES. The sustained intake of a FVOOT improves DNA protection against oxidation and AEES probably due to a greater bioavailability of thyme PC in hyperlipidemic subjects.

Journal of Functional Foods, 2016

This study investigated and compared the absorption, metabolism, and subsequently, the tissue dis... more This study investigated and compared the absorption, metabolism, and subsequently, the tissue distribution and excretion of hydroxytyrosol (HT) administered either in its free form or through its naturally occurring esterified precursors, namely oleuropein (OLE) and its aglycone forms known as secoiridoids (SEC). Here, rats were fed a diet supplemented with the equivalent of 5 mg phenol/kg/day for 21 days and the HT metabolites in the gastrointestinal digesta (stomach, small intestine and caecum), plasma, urine and metabolic tissues (liver and kidney) were analysed. Compared to HT and SEC, OLE showed greater stability during digestion, and, consequently, the bioavailability based on the urine excretion of HT metabolites was higher. OLE, as a glycoside molecule, reached the colon unaltered generating more diverse microbial metabolites. In terms of bioavailability, findings suggest that OLE might be the most suitable precursor of HT for incorporation into foods or nutraceutical formulations.

Molecular nutrition & food research, Jan 21, 2015

Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in free and conjugat... more Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in free and conjugated forms that may exert health benefits against atherosclerosis. The native form of HT is undetectable in plasma due to an extensive first pass phase II metabolism. Therefore, it is necessary to find strategies to obtain HT metabolites and to demonstrate their protective role against the endothelial dysfunction. Biosynthesis of the main plasmatic HT metabolites was performed through Caco-2 cells. The bioactivity of HT and the mixture of metabolites was tested at physiological concentrations (1, 2, 5 and 10 μM) in human aortic endothelial cells (HAEC) co-incubated with TNF-α (10 ng/mL) for 18 and 24 h. After the incubations, cells and media were analyzed to test possible deconjugation of metabolites or conjugation of HT. Both HT and metabolites significantly reduced the secretion of E-selectin, P-selectin, ICAM-1 and VCAM-1, but only HT metabolites further reduced MCP-1 at 24 h. HT underw...

Nutrients, 2022

The impact of a red-fleshed apple (RFA) rich in anthocyanins (ACNs), a white-fleshed apple (WFA) ... more The impact of a red-fleshed apple (RFA) rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an extract infusion from Aronia fruit (AI) equivalent in dose of cyanidin-3-O-galactoside (main ACN) as RFA was determined by the proteome profile of aorta and heart as key cardiovascular tissues. Hypercholesterolaemic Wistar rats were separated into six groups (n = 6/group; three males and three females) and the proteomic profiles were analyzed using nanoliquid chromatography coupled to mass spectrometry. No adverse events were reported and all products were well tolerated. RFA downregulated C1QB and CFP in aorta and CRP in heart. WFA downregulated C1QB and CFP in aorta and C9 and C3 in aorta and heart, among other proteins. AI downregulated PRKACA, IQGAP1, and HSP90AB1 related to cellular signaling. Thus, both apples showed an anti-inflammatory effect through the complement system, while RFA reduced CRP. Regardless of the ACN content, an apple matrix effect was observ...

Molecular Nutrition & Food Research, 2021

Scope: The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new b... more Scope: The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function. Methods and results: A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity. Conclusion: VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function.

Molecular Nutrition & Food Research, 2021

The present study aimed to investigate the metabolic fate and the cardiometabolic effects of phen... more 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 highfat diet (HFD) to induce hypercholesterolemia and supplemented with redfleshed 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 but only in females, probably related to the higher phenol bioavailability reported in females. A decrease in insulin plasma concentration after both apples supplementation was also observed only in males. Our findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3ols, 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.

Journal of Functional Foods, 2021

In a randomized, parallel, double-blind, placebo-controlled trial, participants with elevated blo... more In a randomized, parallel, double-blind, placebo-controlled trial, participants with elevated blood pressure and stage 1 hypertension (n = 159) received 500 mL/day of control drink, orange juice (OJ), or hesperidin-enriched OJ (EOJ) for 12-weeks, and their ischaemic reactive hyperemia (IRH) was assessed at baseline and after 4, 8, and 12-weeks. Two dose-response studies were nested within the sustained-consumption study: at baseline and after 12-weeks, a single dose of 500 mL was administered. All treatments increased postpandrial IRH, and a higher increase was obtained with EOJ. Moreover, hs-CRP and IL6 increased but not after EOJ. After 12 weeks of sustained consumption: IRH values after EOJ increased versus control group; EOJ treatment increased DSP and decreased IEX-1 gene expression in PBMCs; and IRH directly correlated to NO and inversely to MPO and IEX1. Thus, hesperidin in OJ improves human endothelial function, lower inflammatory status at systemic level and changes at transcriptomic level might account for the increased IRH observed.

Scientific Reports, 2020

Hypertension is an independent and preventable risk factor for the development of cardiovascular ... more Hypertension is an independent and preventable risk factor for the development of cardiovascular diseases, however, little is known about the impact of gut microbiota composition in its development. We carried out comprehensive gut microbiota analysis and targeted metabolomics in a cross-sectional study of 29 non-treated hypertensive (HT) and 32 normotensive (NT) subjects. We determined fecal microbiota composition by 16S rRNA gene sequencing and bacterial functions by metagenomic analysis. The microbial metabolites analysed were short chain fatty acids (SCFA) both in plasma and feces, and trimethylamine N-oxide (TMAO) in plasma. The overall bacterial composition and diversity of bacterial community in the two groups were not significantly different. However, Ruminococcaceae NK4A214, Ruminococcaceae_UCG-010, Christensenellaceae_R-7, Faecalibacterium prausnitzii and Roseburia hominis were found to be significantly enriched in NT group, whereas, Bacteroides coprocola, Bacteroides pleb...

Nutrients, 2021

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to... more We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposit...

Food & Function, 2020

This work fills a gap in the understanding of the effect of processing on the bioavailability of ... more This work fills a gap in the understanding of the effect of processing on the bioavailability of (poly)phenols in fruit products.

Molecular Nutrition & Food Research, 2020

European Journal of Nutrition, 2020

Purpose To assess the sustained and acute effects, as well as the influence of sustained consumpt... more Purpose To assess the sustained and acute effects, as well as the influence of sustained consumption on the acute effects, of orange juice (OJ) with a natural hesperidin content and hesperidin-enriched OJ (EOJ) on blood (BP) and pulse (PP) pressures in pre- and stage-1 hypertensive individuals. Methods In a randomized, parallel, double-blind, placebo-controlled trial, participants (n = 159) received 500 mL/day of control drink, OJ, or EOJ for 12 weeks. Two dose–response studies were performed at baseline and after 12 weeks. Results A single EOJ dose (500 mL) reduced systolic BP (SBP) and PP, with greater changes after sustained treatment where a decrease in diastolic BP (DBP) also occurred (P < 0.05). SBP and PP decreased in a dose-dependent manner relative to the hesperidin content of the beverages throughout the 12 weeks (P < 0.05). OJ and EOJ decreased homocysteine levels at 12 weeks versus the control drink (P < 0.05). After 12 weeks of EOJ consumption, four genes relat...

Clinical Nutrition, 2020

Background & aims: The integrity of the intestinal barrier in the diseased is key to prevent furt... more 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 ¼ 6) improves the intestinal barrier integrity and reduces intestinal damage. Additionally, grape seed extract (n ¼ 2), curcumin (n ¼ 1), genistein (n ¼ 1), chlorogenic acid (n ¼ 1), grape pomace (n ¼ 1), olive leaf (n ¼ 1) or cranberry extract (n ¼ 1) improve the intestinal barrier integrity downregulating various inflammatory molecules (TNF-a, 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.

Molecular Nutrition & Food Research, 2018

Journal of Functional Foods, 2019

The aim of this study was to investigate comprehensively the metabolic 27 pathways and human bioa... more The aim of this study was to investigate comprehensively the metabolic 27 pathways and human bioavailability of anthocyanins and other phenolic 28 compounds in apple matrix, and to elucidate potential intake biomarkers. After 29 the acute intake of a red-fleshed apple snack, plasma and urine were collected 30 and analyzed by UPLC-MS/MS. A total of 37 phase-II and microbial phenolic 31 metabolites were detected in plasma and urine. Among these, phloretin 32 glucuronide, cyanidin-3-O-galactoside (plasma and urine) and peonidin-3-O-33 galactoside (urine) were the only metabolites detected in all the volunteers and 34 not detected at basal conditions. The maximum urine excretion was detected at 35 2-4 h, and the main increase in plasma of phloretin glucuronide and cyanidin-3-36 O-galactoside was observed at 2h post-intake (61.0  6.82 and 10.3  1.50 nM, 37 respectively). These metabolites could be selected as the best intake 38 biomarkers of red-fleshed apple that might be useful in human intervention 39 studies when studying the bioactivity of red-fleshed apple.

Molecular nutrition & food research, Aug 29, 2018

The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF) study and othe... more The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF) study and other related studies on the effect of phenol-enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work. VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double-blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80 mg/kg), FVOO (500 mg/kg), and FVOOT (500 mg/kg;1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat-soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing faecal microbial metabolic activity. Additional cardioprotective bene...

The Journal of nutritional biochemistry, 2018

At present, high-density lipoprotein (HDL) function is thought to be more relevant than HDL chole... more At present, high-density lipoprotein (HDL) function is thought to be more relevant than HDL cholesterol quantity. Consumption of olive oil phenolic compounds (PCs) has beneficial effects on HDL-related markers. Enriched food with complementary antioxidants could be a suitable option to obtain additional protective effects. Our aim was to ascertain whether virgin olive oils (VOOs) enriched with (a) their own PC (FVOO) and (b) their own PC plus complementary ones from thyme (FVOOT) could improve HDL status and function. Thirty-three hypercholesterolemic individuals ingested (25 ml/day, 3 weeks) (a) VOO (80 ppm), (b) FVOO (500 ppm) and (c) FVOOT (500 ppm) in a randomized, double-blind, controlled, crossover trial. A rise in HDL antioxidant compounds was observed after both functional olive oil interventions. Nevertheless, α-tocopherol, the main HDL antioxidant, was only augmented after FVOOT versus its baseline. In conclusion, long-term consumption of phenol-enriched olive oils induced...

Molecular nutrition & food research, Oct 25, 2017

Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic o... more Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic of cardiovascular disease. Our aim was to assess short- and long-term effects of virgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with them plus complementary PC from thyme (FVOOT), on PON-related variables and the mechanisms involved. Two randomized, controlled, double-blind, and crossover interventions were conducted. In an acute intake study, participants ingested three FVOOs differing in PC content. In a sustained intake study, participants ingested a control VOO and two different FVOOs with the same PC content but differing in PC source. Acute and sustained intake of VOO and FVOO decreased PON1 protein and increased PON1-associated specific activities, while FVOOT yielded opposite results. PON3 protein levels increased only after sustained consumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolated PC from VOO and fr...

Molecular nutrition & food research, Dec 8, 2017

Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL co... more Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL composition, fluidity, oxidation, and size are related with CEC. We aimed to assess which HDL parameters were CEC determinants after virgin olive oil (VOO) ingestion. Post-hoc analyses from the VOHF study, a crossover intervention with three types of VOO. We assessed the relationship of 3-week changes in HDL-related variables after intervention periods with independence of the type of VOO. After univariate analyses, mixed linear models were fitted with variables related with CEC and fluidity. Fluidity and Apolipoprotein (Apo)A-I content in HDL was directly associated, and HDL oxidative status inversely, with CEC. A reduction in free cholesterol, an increase in triglycerides in HDL, and a decrease in small HDL particle number or an increase in HDL mean size, were associated to HDL fluidity. HDL fluidity, ApoA-I concentration, and oxidative status are major determinants for CEC after VOO. Th...

Molecular nutrition & food research, Oct 29, 2016

Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in both free and com... more Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in both free and complex forms (secoiridoids; SEC). Proteomics of cardiovascular tissues such as aorta or heart represents a promising tool to uncover the mechanisms of action of phenolic compounds in healthy animals. Twelve female Wistar rats were separated into three groups: a standard diet and two diets supplemented in phenolic compounds (HT and SEC) adjusted to 5 mg/kg/day during 21 days. Proteomic analyses of aorta and heart tissues were performed by nano-liquid chromatography and mass spectrometry. Ingenuity Pathway Analysis was used to generate interaction networks. HT or SEC modulated aorta and heart proteome compared to the standard diet. The top-scored networks were related to Cardiovascular System. HT and SEC downregulated proteins related to proliferation and migration of endothelial cells and occlusion of blood vessels in aorta and proteins related to heart failure in heart tissue. SEC showed h...

Journal of Agricultural and Food Chemistry, 2016

The effect of virgin olive oil (VOO) enriched with its own polyphenols (PC) and/or thymephenols o... more The effect of virgin olive oil (VOO) enriched with its own polyphenols (PC) and/or thymephenols on the protection of oxidative DNA damage and antioxidant endogenous enzymatic system (AEES) were estimated in 33 hyperlipidemic subjects after the consumption of VOO, VOO enriched with its own PC (FVOO), or complemented with thyme PC (FVOOT). Compared to pre-intervention, 8-hydroxy-2'-deoxyguanosine (marker for DNA damage) decreased in the FVOO intervention and to a greater extent in the FVOOT with a parallel significant increase in olive and thyme phenolic biomarkers. Superoxide Dismutase (AEES enzyme) significantly increased in the FVOO intervention and to a greater extent in the FVOOT with a parallel significant increase in thyme phenolic metabolites. When comparing all three oils, FVOOT appeared to have the greatest effect in protecting against oxidative DNA damage and improving AEES. The sustained intake of a FVOOT improves DNA protection against oxidation and AEES probably due to a greater bioavailability of thyme PC in hyperlipidemic subjects.

Journal of Functional Foods, 2016

This study investigated and compared the absorption, metabolism, and subsequently, the tissue dis... more This study investigated and compared the absorption, metabolism, and subsequently, the tissue distribution and excretion of hydroxytyrosol (HT) administered either in its free form or through its naturally occurring esterified precursors, namely oleuropein (OLE) and its aglycone forms known as secoiridoids (SEC). Here, rats were fed a diet supplemented with the equivalent of 5 mg phenol/kg/day for 21 days and the HT metabolites in the gastrointestinal digesta (stomach, small intestine and caecum), plasma, urine and metabolic tissues (liver and kidney) were analysed. Compared to HT and SEC, OLE showed greater stability during digestion, and, consequently, the bioavailability based on the urine excretion of HT metabolites was higher. OLE, as a glycoside molecule, reached the colon unaltered generating more diverse microbial metabolites. In terms of bioavailability, findings suggest that OLE might be the most suitable precursor of HT for incorporation into foods or nutraceutical formulations.

Molecular nutrition & food research, Jan 21, 2015

Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in free and conjugat... more Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in free and conjugated forms that may exert health benefits against atherosclerosis. The native form of HT is undetectable in plasma due to an extensive first pass phase II metabolism. Therefore, it is necessary to find strategies to obtain HT metabolites and to demonstrate their protective role against the endothelial dysfunction. Biosynthesis of the main plasmatic HT metabolites was performed through Caco-2 cells. The bioactivity of HT and the mixture of metabolites was tested at physiological concentrations (1, 2, 5 and 10 μM) in human aortic endothelial cells (HAEC) co-incubated with TNF-α (10 ng/mL) for 18 and 24 h. After the incubations, cells and media were analyzed to test possible deconjugation of metabolites or conjugation of HT. Both HT and metabolites significantly reduced the secretion of E-selectin, P-selectin, ICAM-1 and VCAM-1, but only HT metabolites further reduced MCP-1 at 24 h. HT underw...