Juan Carlos Espín

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Verified

Juan Carlos verified their affiliation via an institutional email.

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• Biological Sciences PhD
• Full Research Professor at Spanish National Research Council

Scope Some polyphenol‐derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. We evaluated here their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly‐diagnosed BC patients and explored the tissue‐occu...

Despite the high human interindividual variability in response to (poly)phenol consumption, the cause-and-effect relationship between some dietary (poly)phenols (flavanols and olive oil phenolics) and health effects (endothelial function and prevention of LDL oxidation, respectively) has been well established. Most of the variables affecting this i...

We describe here for the first time the consistent observation of two metabotypes associated with resveratrol metabolism by the human gut microbiota, that is, lunularin (LUNU)-producers and LUNU non-producers. In healthy volunteers (n = 195), resveratrol was reduced to dihydroresveratrol, which only in the LUNU-producer metabotype was sequentially...

Personalized nutrition” aims to establish nutritional strategies to improve health outcomes for non‐responders. However, it is utopian since most people share similar nutritional requirements. “Precision health,” encompassing lifestyles, may be more fitting. Dietary (poly)phenols are “healthy” but non‐nutritional molecules (thus, we can live withou...

Many physical, social, and psychological changes occur during aging that raise the risk of developing chronic diseases, frailty, and dependency. These changes adversely affect the gut microbiota, a phenomenon known as microbe-aging. Those microbiota alterations are, in turn, associated with the development of age-related diseases. The gut microbiot...

Dietary (poly)phenols are metabolized by intestinal microbiota, but their potential effect on intestinal gas production and gas-reated symptoms remain uncertain. The aim of this study was to correlate gas production, digestive sensations, gut microbiota composition, and metabolites in urine and feces upon (poly)phenols consumption. Twenty-three hea...

Echinacea purpurea L. (EP) preparations are globally popular herbal supplements known for their medicinal benefits, including anti-inflammatory activities, partly related to their phenolic composition. However, regarding their use for the management of inflammation-related intestinal diseases, the knowledge about the fate of orally ingested constit...

Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy is either increased or unchanged in...

The metabolism of (poly)phenols and some host metabolites, including bile acids (BAs) and cholesterol, varies among individuals depending on their gut microbiota. The gut microbial metabolism of ellagitan-nins (ETs) and ellagic acid (EA) produces urolithins (Uros), yielding three metabotypes with quantitative and qualitative differences based on di...

Current knowledge indicates that the consumption of isoflavone-rich foodstuffs can have a beneficial impact on cardiovascular health. Less clear is to what extent these isoflavones act as the main actors...

Urolithins are gut microbiota metabolites of ellagic acid. Here, we have identified and chemically characterized a novel urolithin produced from urolithin D (3,4,8,9-tetrahydroxy urolithin) by in vitro incubation with different human gut Enterocloster species under anaerobic conditions. Urolithin G (3,4,8-trihydroxy urolithin) was identified by 1H...

Background: This study aimed to evaluate the effect of pomegranate juice intake on the inflammatory status and complete blood count in hospitalized Covid-19 patients. Methods: This randomized, double-blinded placebo-controlled trial included 48 patients with two parallel arms. In addition to the standard care provided at the hospital, the patien...

Niemann Pick diseases types A (NPDA) and C (NPDC) are lysosomal storage disorders (LSDs) leading to cognitive impairment, neurodegeneration, and early death. NPDA and NPDC have different genetic origins, being caused by mutations in the acid sphingomyelinase (ASM) or the cholesterol transport protein NPC1, respectively. However, they share a common...

Urolithin (Uro) production capacity and, consequently, at least partly, the health effects attributed to ellagitannin and ellagic acid consumption vary among individuals. The reason is that not all individuals have the gut bacterial ecology needed to produce the different Uro metabolites. Three human urolithin metabotypes (UM-A, UM-B, and UM-0) bas...

We aimed to elucidate the gut bacteria that characterize the human urolithin metabotypes A and B (UM-A and UM-B). We report here a new bacterium isolated from the feces of a healthy woman, capable of producing the final metabolites urolithins A and B and different intermediates. Besides, we describe two gut bacterial co-cultures that reproduced the...

The metabolism of (poly)phenols and some host metabolites, including bile acids (BAs) and cholesterol, vary among individuals depending on their gut microbiota. The gut microbial metabolism of ellagitannins (ETs) and...

Effective strategies in prolonging life- and health span are increasingly recognized as acting as mild stressors. Micronutrients and other dietary compounds such as (poly)phenols may act as moderate stressors and confer protective effects via a preconditioning phenomenon. (Poly)phenols and their metabolites may not need to reach their target cells...

trans-Resveratrol can be catabolized by the gut microbiota to dihydroresveratrol, 3,4′-dihydroxy-trans-stilbene, lunularin, and 4-hydroxydibenzyl. These metabolites can reach relevant concentrations in the colon. However, not all individuals metabolize RSV equally, as it depends on their RSV gut microbiota metabotype (i.e., lunularin producers vs....

Previous studies have shown that a resistant dextrin-soluble fibre has prebiotic properties with related health benefits on blood glucose management and satiety. Our aim was to demonstrate the effects of continuous administration of resistant dextrin on intestinal gas production, digestive sensations, and gut microbiota metabolism and composition....

El.la.gi.bac'ter. N.L. neut. n. acidum ellagicum ellagic acid; N.L. masc. n. bacter rod; N.L. masc. n. Ellagibacter ellagic acid‐transforming rod. Actinomycetota / Coriobacteriia / Eggerthellales / Eggerthellaceae / Ellagibacter The genus Ellagibacter accommodates human intestinal bacteria capable of transforming dietary phenolic compounds such as...

Exosomes are extracellular vesicles (EVs) that regulate intercellular signaling by transferring small RNAs, proteins, nucleic acids, lipids, and other metabolites to local or distant organs, including the brain, by crossing the blood–brain barrier. However, the transport of (poly)phenols in human EVs has not yet been described. Therefore, we aimed...

Ellagitannins (ETs) and ellagic acid (EA) are dietary polyphenols poorly absorbed but extensively metabolized by the human gut microbiota to produce different urolithins (Uros). Depending on the individuals' microbial signatures , ETs metabolism can yield the Uro metabotypes A, B, or 0, potentially impacting human health after consuming ETs. Human...

Resveratrol (RSV) was known to be metabolised by the gut micro-biota to dihydroresveratrol, lunularin (LUNU), and (or) 3,4'-dihy-droxy-trans-stilbene (DHST). We describe here for the first time that LUNU can be further dehydroxylated, but only at the 3-position , to yield 4-hydroxydibenzyl, a novel metabolite found in human urine after RSV intake i...

Angiogenesis is a complex process encompassing endothelial cell proliferation, migration, and tube formation. While numerous studies describe that curcumin exerts antitumor properties (e.g., targeting angiogenesis), information regarding other dietary curcuminoids such as demethoxycurcumin (DMC) and bisdemethoxycurcumin (BisDMC) is scant. In this s...

Gut microbiota alteration (gut dysbiosis) occurs during the onset and progression of Parkinson's disease. Gut dysbiosis biomarkers could be relevant to prodromal disease. Urolithins, anti-inflammatory metabolites produced from some dietary polyphenols by specific gut microbial ecologies (urolithin metabotypes), have been proposed as biomarkers of g...

Berry fruits are rich in polyphenolic compounds (PCs) and may promote health benefits. Anthocyanin (ACN) concentrations of red raspberry (RR) (Rubus idaeus) extracts were 887.6 ± 262.8 μg g-1, consisting mainly of cyanidin-3-sophoroside (C3S) equivalents. To test the efficacy of RR in diabetes treatment, seven patients with type 2 diabetes mellitus...

Gor.do.ni.bac'ter. N.L. masc. n. bacter , a rod; N.L. masc. n. Gordonibacter , a rod named after Jeffrey I. Gordon, the Dr. Robert J. Glaser Distinguished University Professor and Director of the Center for Genome Sciences at Washington University School of Medicine, St. Louis, MO, USA; N.L. masc. n. bacter a rod; N.L. masc. n. Gordonibacter a rod...

Dietary (poly)phenols are extensively metabolized, limiting their anticancer activity. Exosomes (EXOs) are extracellular vesicles that could protect polyphenols from metabolism. Our objective was to compare the delivery to breast tissue and anticancer activity in breast cancer cell lines of free curcumin (CUR) and resveratrol (RSV) vs. their encaps...

This study aimed to characterize an animal model of colorectal cancer (CRC) in the early stages of disease development. Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2), receiving EDTA-saline injections and two induced groups (CRC1 and CRC2), receiving 1,2-dimethylhydrazine (DMH) injections for seven consecutive w...

Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, were discovered by our research group in humans almost twenty years ago. Pioneering research suggested urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin‐rich sources (pomegranates, wa...

Abstract: Our aim was to determine the effect of diet on gut microbiota, digestive function and sensations, using an integrated clinical, metagenomics and metabolomics approach. We conducted a cross-over, randomised study on the effects of aWestern-type diet versus a fibre-enriched Mediterranean diet. In 20 healthy men, each diet was administered f...

5-Lipoxygenase (5-LOX) plays a key role in inflammation through the biosynthesis of leukotrienes and other lipid mediators. Current evidence suggests that dietary (poly)phenols exert a beneficial impact on human health through anti-inflammatory activities. Their mechanisms of action have mostly been associated with the modulation of pro-inflammator...

Background The consumption of pomegranate juices and extracts has long been linked to many health benefits beyond nutrition, described mainly by innumerable preclinical studies. However, the European Food Safety Authority (EFSA) concluded in 2010 that a cause and effect relationship could not be established between the consumption of pomegranate-de...

The intake of hesperidin-rich sources, mostly found in orange juice, can decrease cardiometabolic risk, potentially linked to the gut microbial phase-II hesperetin derivatives. However, the low hesperidin solubility hampers its bioavailability and microbial metabolism, yielding a high inter-individual variability (high vs. low-producers) that preve...

Scope Poly‐pharmacological therapy shapes the gut microbiota (GM) in metabolic syndrome (MetS) patients. The effects of polyphenol‐rich sources in poly‐medicated MetS patients are unknown. Methods and Results A randomized, placebo‐controlled, double‐blinded, and crossover trial in poly‐medicated MetS patients (n = 50) explored whether the effects...

The most relevant food components in the interaction with gut microbes are (poly)phenols and complex carbohydrates (prebiotics). (Poly)phenols include a large family of secondary metabolites that ubiquitous in plant-derived foods. Their absorption in the small intestine is very low, and therefore they have extensive interaction with the gut microbi...

The gut microbiota transforms most dietary polyphenols (90%) in the intestine of humans and other mammals. This conversion is often essential for absorption and controls the biological activity of these compounds. Different studies have been performed to understand how gut microbiota transforms the different polyphenols into smaller molecules calle...

The hydrolyzable tannins ellagitannins (ETs) and ellagic acid (EA) are polyphenols present in food sources such as pomegranates, berries, and walnuts. However, they are poorly absorbed on consumption, but the gut microbiota metabolizes them. In recent decades, an extensive literature has attributed a wide range of beneficial effects to these natura...

The maternal−infant transmission of several urolithins through breast milk and the gut colonization of infants by the urolithin-producing bacterium Gordonibacter during their first year of life were explored. Two trials (proof-of-concept study: n = 11; validation study: n = 30) were conducted, where breastfeeding mothers consumed walnuts as a dieta...

Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death in adult women worldwide. Over 85% of BC cases are non-hereditary, caused by modifiable extrinsic factors related to lifestyle, including dietary habits, which play a crucial role in cancer prevention. Although many epidemiological and observational studi...

Gordonibacter urolithinfaciens and Ellagibacter isourolithinifaciens are two human gut bacterial species that convert ellagic acid into urolithins. Urolithins are bioactive postbiotics produced by dehydroxylation reactions catalyzed by different dehydroxylases. The metabolic ability of these anaerobic bacteria on other dietary- phenolic compounds i...

Environmental and genetic factors are associated with pandemic obesity since childhood. However, the association of overweight-obesity with these factors, acting as a consortium, has been scarcely studied in children. We aimed here to assess the probabilities of being overweighed-obese in a randomly recruited cohort of Spanish children and adolesce...

Scope Urolithins, gut microbial metabolites derived from ellagic acid (EA), reach significant concentrations in the human colon. Urolithin‐A (Uro‐A) exerts anti‐inflammatory activity in animal models of inflammatory bowel diseases (IBDs). We hypothesized that urolithins could modulate the biosynthesis of leukocyte‐derived inflammatory eicosanoids f...

The full consensus on the role of dietary polyphenols as human health‐promoting compounds remains elusive. The two‐way interaction between polyphenols and gut microbiota (GM) (i.e., modulation of GM by polyphenols and their catabolism by the GM) is determinant in polyphenols’ effects. The identification of human metabotypes associated with a differ...

The gut microbiota (GM) has attracted attention as a new target to combat several diseases, including metabolic syndrome (MetS), a pathological condition with many factors (diabetes, obesity, dyslipidemia, hypertension, etc.) that increase cardiovascular disease (CVD) risk. However, the existence of a characteristic taxonomic signature associated w...

The promotion of senescence in cancer cells by dietary (poly)phenols gained attention as a promising chemopreventive strategy against colorectal (CRC) and other cancers. Urolithins (Uros) are ellagitannins and ellagic acid-derived gut microbiota metabolites that reach high concentrations in the human colon. They were postulated to be as potential a...

Environmental and genetic factors are associated with pandemic obesity since childhood. However, the association of overweight-obesity with these factors, acting as a consortium, has been scarcely studied in children. We aimed here to assess the probabilities of being overweighed-obese in a randomly recruited cohort of Spanish children and adolesce...

Walnuts are rich in polyphenols ellagitannins, modulate gut microbiota (GM), and exert health benefits after long-term consumption. The metabolism of ellagitannins to urolithins via GM depends on urolithin metabotypes (UM-A, -B, or -0), which have been reported to predict host responsiveness to a polyphenol-rich intervention. This study aims to ass...

Urolithins are bioactive gut microbiota metabolites of ellagic acid. Here we have identified four unknown urolithins in human feces after the intake of a pomegranate extract. The new metabolites occurred only in 19% of the subjects. 4,8,9,10-Tetrahydroxy urolithin (urolithin M6R), was unambiguously identified by 1H NMR, UV, and HRMS. Three metaboli...

The metabolism of dietary polyphenols ellagitannins by the gut-microbiota allows the human stratification in urolithin metabotypes depending on the final urolithins produced. Metabotype-A only produces urolithin-A, metabotype-B yields urolithin-B and isourolithin-A in addition to urolithin-A, and metabotype 0 does not produce urolithins. Metabotype...

We recently showed that methylxanthines and conjugated phenolic-derived metabolites reached the mammary tissue (MT) of breast cancer patients after consuming a blend of phenolic-rich extracts. The pre-surgery fasting could prevent the detection of some (including those non-conjugated) metabolites. We investigated here the pharmacokinetics in rat pl...

Scope: Recent evidence demonstrates that resveratrol (RSV) metabolites, but not free RSV, reach malignant tumours (MT) in breast cancer (BC) patients. Since these metabolites, as detected in MT, do not exert short-term antiproliferative or estrogenic/antiestrogenic activities, long-term tumour-senescent chemoprevention has been hypothesised. Conse...

Urolithin A (Uro-A) is an anti-inflammatory and cancer chemopreventive metabolite produced by the gut microbiota from the polyphenol ellagic acid. However, in vivo conjugation of Uro-A to Uro-A glucuronide (Uro-A glur) dramatically hampers its activity. We describe here for the first time the tissue deconjugation of Uro-A glur to Uro-A after lipopo...

The two-way interaction of food (poly)phenols with the human gut microbiota has been studied throughout the past ten years. Research has shown that this interaction can be relevant to explain the health effects of these phytochemicals. The effect of the food matrix and food processing on this interaction has only been partially studied. In this art...

Monacolin K (MK, lovastatin), a natural-occurring statin, only exerts lipid-lowering effects in its active b-hydroxy acid form (MKA). This activation was thought to be mediated by the gut microbiota (GM)....

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a clonal disease of blood cells caused by the lack of glycosyl phosphatidyl inositol anchored proteins bound to the cell membrane. In consequence, erythrocytes lead to intravascular hemolysis upon complement activation, which promotes high risk of thrombosis, intravascular hemolytic anemia, and bone marr...

Scope: Dietary polyphenols may protect against breast cancer. However, it is unknown whether polyphenols reach human malignant breast tumours in molecular forms and(or) at concentrations likely to act against cancer. Methods & Results: Breast cancer patients (n = 19) consumed three capsules daily from biopsy‐confirmed diagnosis to surgery (6 ± 2 da...

Urolithins (e.g., UroA and B) are gut microbiota-derived metabolites of the natural polyphenol ellagic acid. Urolithins are associated with various health benefits, including attenuation of inflammatory signaling, anti-cancer effects and repression of lipid accumulation. The molecular mechanisms underlying the beneficial effects of urolithins remai...

Scope The stratification of individuals according to their gut microbiota metabotypes is crucial to understand the polyphenols health effects as reported for isoflavones and ellagitannins. To date, the existence of human gut microbiota metabotypes associated with proanthocyanidins (PAs) catabolism remains unclear. Methods & Results Sixty‐eight hea...

Scope The gut microbiota ellagitannin‐metabolizing phenotypes (i.e. urolithin metabotypes, UMs) have been proposed as potential cardiovascular disease (CVD) risk biomarkers because the host blood lipid profile was reported to be associated with specific UMs. However, the link for this association remains unknown so far. Methods & Results We analys...

Urolithins (e.g., UroA and B) are gut microbiota-derived metabolites of the natural polyphenol ellagic acid. Urolithins are associated with various health benefits, including attenuation of inflammatory signaling, anti-cancer effects and repression of lipid accumulation. The molecular mechanisms underlying the beneficial effects of urolithins remai...

Combining natural products as co-adjuvants in 5-fluorouracil (5-FU) chemotherapy might enhance the effectiveness of 5-FU by avoiding a high dosage and/or reducing treatment times. We explored the anticancer efficacy of the phytosterols (PS) at concentrations achievable in the human colon, as well as their potential as sensitizing agents of human co...

‘Our results suggest potential health beneficial effects although further in vivo studies are needed…’ Perhaps, this is the most repeated conclusion in the in vitro studies dealing with dietary (poly)phenols in the last decades. Since early epidemiological and observational studies suggested that dietary (poly)phenols could play an important prote...

While preclinical studies suggest the breast cancer (BC) chemopreventive effects of dietary polyphenols, the human evidence is still very weak. The huge existing in vitro-in vivo gap is mainly due to the plethora of potential effects reported by in vitro studies that usually assay polyphenols as occurring in the food (beverages, extracts, foods) an...

Understanding individuals’ response to dietary bioactives is crucial for personalized nutrition. We report here for the first time in a Caucasian cohort (5-90 years, n=839) that aging is the main...

Gut microbiota dysbiosis alters the intestinal barrier function, increases plasma lipopolysaccharide (LPS) levels, which promotes endotoxemia, and contributes to the onset and development of colorectal cancer (CRC). We report here...

Scope Gut microbiota dysbiosis, intestinal barrier failure, obesity, metabolic endotoxemia and pro‐inflammatory status promote cardiovascular risk. However, the modulation of the gut microbiome to prevent endotoxemia in obesity has been scarcely studied. We investigated the association between gut microbiota modulation and plasma lipopolysaccharide...

Urolithins are gut microbial metabolites that exert health benefits in vivo and are generated from ellagic acid (EA) and ellagitannin-containing foods such as strawberries, pomegranates and walnuts. Gordonibacter species produce some intermediary urolithins but the micro-organisms responsible for the transformation of EA into the final and more bio...

Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources...

Background Flaxseed is the most common and rich dietary source of lignans and is an acceptable supply of energy for livestock. Flaxseed lignans are precursors of enterolignans, mainly enterolactone and enterodiol, produced by the rumen and intestinal microbiota of mammals and have many important biological properties as phytoestrogens. Potential fo...

Gordonibacter urolithinfaciens DSM 27213 T was isolated from human feces and is able to metabolize ellagic acid (a dietary phenolic compound present in various fruits) to urolithins. Here, we report the finished and annotated genome sequence of this organism.

Lignans are dietary polyphenols, which are metabolized by the gut microbiota into the phytoestrogenic metabolites enterolignans, mainly enterolactone and enterodiol. The Breast Cancer Resistance Protein (BCRP/ABCG2) is an efflux transporter that affects plasma and milk secretion of several drugs and natural compounds. We hypothesized here that Abcg...

Urolithins are intestinal microbial metabolites produced from ellagitannin- and ellagic acid-containing foods such as walnuts, strawberries, and pomegranates. These metabolites, better absorbed than their precursors, can contribute significantly to the beneficial properties attributed to the polyphenols ellagitannins and ellagic acid (EA). However,...

Lignans are phytoestrogens widely used in dietary supplements and functional foods. After oral ingestion, these polyphenols are metabolized to enterolignans, the main gut microbiota-derived metabolites with weak estrogenic/anti-estrogenic activities. The ABCG2 transporter is highly expressed in the mammary gland and could be responsible for enterol...

Recent studies demonstrate that fruits are rich in non-extractable polyphenols, macro-antioxidants, which have been underestimated. These are not absorbed and reach the colon where are catabolized by human gut microbiota releasing low molecular weight phenolics that are then absorbed efficiently. These metabolites persist in human plasma for extend...

A complete characterization of the phenolic profile of leaves infusions from seven Mexican Quercus species was developed using different LC-DAD-MS/MS methodologies. The main families of phenolic compounds identified and quantified were: hydrolyzable tannins and flavonol glycosides, based on their fragmentation patterns and UV spectra, proanthocyani...

A TWIN-SHIME® system was used to compare the metabolism of pomegranate polyphenols by the gut microbiota from two individuals with different urolithin metabotypes. Gut microbiota, ellagitannin metabolism, short-chain fatty acids (SCFA), transport of metabolites and phase II metabolism using Caco-2 cells were explored. The simulation reproduced the...

Scope: The pomegranate lipid-lowering properties remain controversial, probably due to the interindividual variability in polyphenol (ellagitannins) metabolism. Objective: We aimed at investigating whether the microbial-derived ellagitannin-metabolizing phenotypes, i.e. urolithin metabotypes A, (UM-A), B (UM-B) and 0 (UM-0), influence the effect...

Purpose: Urolithins, metabolites produced by the gut microbiota from ellagic acid, have been acknowledged with cancer chemopreventive activity. Although urolithin A (Uro-A) has been reported to be the most active one, 10-50 % of humans can also produce the isomer isourolithin A (IsoUro-A). However, no biological activity for IsoUro-A has been repo...

Background & aims: Urolithins are microbial metabolites produced after consumption of ellagitannin-containing foods such as pomegranates and walnuts. Parallel to isoflavone-metabolizing phenotypes, ellagitannin-metabolizing phenotypes (urolithin metabotypes A, B and 0; UM-A, UM-B and UM-0, respectively) can vary among individuals depending on thei...