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1.
J Agric Food Chem ; 71(31): 11921-11928, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37494568

RESUMEN

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 NMR, 13C NMR, UV, HRMS, and 2D NMR. For the identification, NMR spectra of other known urolithins were also recorded and compared. Urolithin G was present in the feces of 12% of volunteers in an overweight-obese group after consuming an ellagitannin-rich pomegranate extract. The production of urolithin G required a bacterial 9-dehydroxylase activity and was not specific to the known human urolithin metabotypes A and B. The ability to produce urolithin G could be considered an additional metabolic feature for volunteer stratification and bioactivity studies. This is the first urolithin with a catechol group in ring A while having only one hydroxyl in ring B, a unique feature not found in human and animal samples so far.


Asunto(s)
Microbioma Gastrointestinal , Obesidad , Animales , Humanos , Heces/microbiología , Obesidad/metabolismo , Sobrepeso , Cumarinas/química , Taninos Hidrolizables/metabolismo
2.
J Agric Food Chem ; 71(9): 4029-4035, 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36840624

RESUMEN

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 urolithin formation pathways upon in vitro fermentation of both UM-A and UM-B. This is the first time that the capacity of pure strains to metabolize ellagic acid cooperatively to yield urolithin profiles associated with UM-A and UM-B has been demonstrated. The urolithin-producing bacteria described herein could have potential as novel probiotics and in the industrial manufacture of bioactive urolithins to develop new ingredients, beverages, nutraceuticals, pharmaceuticals, and (or) functional foods. This is especially relevant in UM-0 individuals since they cannot produce bioactive urolithins.


Asunto(s)
Ácido Elágico , Microbioma Gastrointestinal , Femenino , Humanos , Ácido Elágico/metabolismo , Heces/microbiología , Cumarinas/metabolismo , Bacterias , Taninos Hidrolizables/metabolismo
3.
Food Funct ; 11(8): 7012-7022, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32716447

RESUMEN

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 catechol-dehydroxylases. The metabolic ability of these anaerobic bacteria on other dietary-phenolic compounds is unknown. In the present study, we evaluated the metabolism of flavonoids (quercetin, hesperetin, hesperidin, nobiletin, catechin, isoxanthohumol), isoflavonoids (daidzein), coumarins (esculetin, umbelliferone, scoparone), phenylpropanoids [caffeic acid; 3-(3',4'-dihydroxyphenyl)propanoic acid (dihydrocaffeic acid); rosmarinic acid, and chlorogenic acid], benzoic acid derivatives (gallic acid, ellagic acid), lignans (secoisolariciresinol diglucoside), stilbenes (resveratrol), and secoiridoids (oleuropein) by G. urolithinfaciens DSM 27213T and E. isourolithinifaciens DSM 104140T. Both strains metabolized ellagic acid leading to the characteristic urolithins. They also metabolized caffeic, dihydrocaffeic, rosmarinic, and chlorogenic acids. The rest of the phenolic compounds were not transformed. Catechol dehydroxylation and double bond reduction were prominent transformations observed during the incubations. The enzymatic activities seem to have a narrow substrate scope as many catechol- (quercetin, catechin, esculetin, gallic acid) and double bond-containing (resveratrol, esculetin, scoparone, umbelliferone) phenolics were not metabolized. The catechol-dehydroxylase activity was more efficient in E. isourolithinifaciens, while the reductase activity was more relevant in G. urolithinfaciens.


Asunto(s)
Actinobacteria/metabolismo , Ácido Elágico/metabolismo , Oxigenasas de Función Mixta/metabolismo , Fenoles/metabolismo , Catecoles/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Hidroxilación
5.
Thromb Res ; 183: 80-85, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31671376

RESUMEN

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease in which patients are at increased risk of thrombosis. The mechanisms underlying the associated thrombosis risk are still poorly understood, although it is known that Eculizumab, the drug of choice for symptomatic patients, prevents thrombotic events. Exosomes are extracellular vesicles that can carry and disseminate genetic material, tumor biomarkers and inflammatory mediators. To date, the metabolite cargo of plasma exosomes from PNH patients has not yet been explored. In this pilot trial, we compared the metabolome of plasma exosomes from PNH patients with that of healthy subjects in order to provide further insights into this rare disease. RESULTS: We used a non-targeted metabolomics approach with UPLC-ESI-QTOF-MS/MS and GC-MS platforms. Multivariate analyses revealed the differential occurrence (p < .001) of 78 metabolites in plasma exosomes from PNH patients vs healthy control subjects. Remarkably, prostaglandin F2-alpha (6.1-fold), stearoyl arginine (5.3-fold) and 26-hydroxycholesterol-3-sulfate (11.2-fold) were higher in PNH patients vs healthy controls (p < .001). CONCLUSIONS: This is the first description on the differential metabolite cargo occurring in plasma exosomes from PNH patients. Our results could contribute to the search for possible prognostic biomarkers of thrombotic risk in patients with PNH. Further research in a larger cohort to validate these results is warranted.


Asunto(s)
Exosomas/fisiología , Hemoglobinuria Paroxística/genética , Metaboloma/fisiología , Trombosis/etiología , Adolescente , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto
6.
J Agric Food Chem ; 67(40): 11099-11107, 2019 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-31496244

RESUMEN

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 metabolites were tentatively identified by the UV, HRMS, and chromatographic behavior, as 4,8,10-trihydroxy (urolithin M7R), 4,8,9-trihydroxy (urolithin CR), and 4,8-dihydroxy (urolithin AR) urolithins. Phase II conjugates of the novel urolithins were detected in urine and confirmed their absorption, circulation, and urinary excretion. The production of the new urolithins was not specific of any of the known urolithin metabotypes A and B. The new metabolites needed a bacterial 3-dehydroxylase activity for their production, and this is a novel feature as all the previously known urolithins maintained the hydroxyl at 3 position. The ability of production of these "R" urolithins can be considered an additional metabolic feature for volunteer stratification.


Asunto(s)
Cumarinas/metabolismo , Heces/química , Lythraceae/metabolismo , Obesidad/dietoterapia , Extractos Vegetales/metabolismo , Orina/química , Adulto , Anciano , Cumarinas/química , Ácido Elágico/química , Ácido Elágico/metabolismo , Femenino , Humanos , Lythraceae/química , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Obesidad/orina , Extractos Vegetales/química
7.
Annu Rev Food Sci Technol ; 10: 221-238, 2019 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-30633563

RESUMEN

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 article, the studies within this field have been critically reviewed, with a special focus on the following groups of phenolic metabolites: citrus flavanones, pomegranate ellagitannins, and cocoa proanthocyanidins. The available research shows that both the food matrix and food processing can be relevant factors for gut microbiota reshaping to reach a healthier microbial ecology and for the conversion of polyphenols to bioactive and bioavailable metabolites. There are, however, some research gaps that indicate a more comprehensive research approach is needed to reach valid conclusions regarding the gut microbiota-mediated effects of polyphenols on human health.


Asunto(s)
Alimentos , Microbioma Gastrointestinal , Humanos , Polifenoles/metabolismo , Prebióticos
8.
Metabolites ; 8(4)2018 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-30501068

RESUMEN

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 remain unclear. We hypothesize that some of the human health benefits of urolithins are mediated through the aryl hydrocarbon receptor (AHR). Utilizing a cell-based reporter system, we tested urolithins for the capacity to modulate AHR activity. Cytochrome P450 1A1 (CYP1A1) mRNA levels were assessed by real-time quantitative polymerase chain reaction. Competitive ligand binding assays were performed to determine whether UroA is a direct ligand for the AHR. Subcellular AHR protein levels were examined utilizing immunoblotting analysis. AHR expression was repressed in Caco-2 cells by siRNA transfection to investigate AHR-dependency. UroA and B were able to antagonize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced AHR-mediated transcriptional activity. Furthermore, UroA and B attenuated TCDD-mediated stimulation of CYP1A1 mRNA levels. In addition, competitive ligand binding assays characterized UroA as a direct AHR ligand. Consistent with other AHR antagonists, UroA failed to induce AHR retention in the nucleus. AHR is necessary for UroA-mediated attenuation of cytokine-induced interleukin 6 (IL6) and prostaglandin-endoperoxide synthase 2 (PTGS2) expression in Caco-2 cells. Here we identified UroA as the first dietary-derived human selective AHR antagonist produced by the gut microbiota through multi-step metabolism. Furthermore, previously reported anti-inflammatory activity of UroA may at least in part be mediated through AHR.

10.
Int J Syst Evol Microbiol ; 68(5): 1707-1712, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29583112

RESUMEN

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 bioactive urolithins, such as urolithin A and isourolithin A, are unknown. We report here a new bacterium, capable of metabolizing EA into isourolithin A, isolated from healthy human faeces and characterized by determining phenotypic, biochemical and molecular methods. Strain CEBAS 4A belongs to the Eggerthellaceae family and differed from other genera of this family, both phylogenetically and phenotypically. Based on 16S rRNA gene sequence similarity, the strain was related to Enterorhabdus musicola DSM 19490T (92.9 % similarity), Enterorhabdus caecimuris DSM 21839T (92.7 % similarity), Adlercreutzia equolifaciens DSM 19450T (92.5 % similarity), Asaccharobacter celatus DSM 18785T (92.5 % similarity) and Parvibacter caecicola DSM 22242T (91.2 % similarity). This strain was strictly anaerobic and Gram-stain-positive. The whole-cell fatty acids were saturated (98.3 %), a very high percentage that differs from the nearest genera ranging from 62 to 73 %. The major respiratory lipoquinone was menaquinone-7 and the diamino acid in the peptidoglycan was meso-diaminopimelic acid. Diphosphatidylglycerol and phosphatidylglycerol comprised the main polar lipid profile in addition to several phosphoglycolipids (PGL1-2), phospholipids (PL1-4), glycolipids (GL1-6) and lipids. Based on these data, a new genus, Ellagibacter gen. nov. is proposed with one species, Ellagibacter isourolithinifaciens sp. nov. The type strain of Ellagibacter isourolithinifaciens is CEBAS 4AT (=DSM 104140T=CCUG 70284T).


Asunto(s)
Actinobacteria/clasificación , Tracto Gastrointestinal/microbiología , Filogenia , Actinobacteria/genética , Actinobacteria/aislamiento & purificación , Adulto , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácido Diaminopimélico , Ácidos Grasos/química , Heces/microbiología , Glucolípidos/química , Humanos , Masculino , Peptidoglicano/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
11.
Food Funct ; 9(1): 636-642, 2018 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-29292449

RESUMEN

Lignans are dietary polyphenols, which are metabolized by gut microbiota into the phytoestrogenic metabolites enterolignans, mainly enterolactone and enterodiol. Breast Cancer Resistance Protein (BCRP/ABCG2) is an efflux transporter that affects the plasma and milk secretion of several drugs and natural compounds. We hypothesized here that Abcg2 could influence the levels of lignans and their derived metabolites in target tissues. Consequently, we aimed to evaluate the role of Abcg2 in the tissue distribution of these compounds. We used Abcg2-/- knockout and wild-type male mice fed with a lignan-enriched diet for one week and analysed their plasma, small intestine, colon, liver, kidneys and testicles. High levels of lignans as well as enterolignans and their glucuronide and sulfate conjugates in the small intestine and colon were detected, with higher concentrations of the conjugates in the wild-type compared with Abcg2-/- mice. Particularly relevant was the detection of 24-fold and 8-fold higher concentrations of enterolactone-sulfate and enterolactone-glucuronide, respectively, in the kidney of Abcg2-/- compared with wild-type mice. In conclusion, our study showed that lignans and their derived metabolites were in vivo substrates of Abcg2, which affected their plasma and tissue levels. These results highlight the role of Abcg2 in influencing the health-beneficial properties of dietary lignans.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/deficiencia , Lino/metabolismo , Lignanos/metabolismo , Extractos Vegetales/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Animales , Femenino , Lino/química , Lignanos/química , Masculino , Ratones , Ratones Noqueados , Extractos Vegetales/química , Distribución Tisular
12.
Clin Nutr ; 37(3): 897-905, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-28347564

RESUMEN

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 their body mass index (BMI), but correlations between urolithin metabotypes (UMs) and cardiometabolic risk (CMR) factors are unexplored. We investigated the association between UMs and CMR factors in individuals with different BMI and health status. METHODS: UM was identified using UPLC-ESI-qToF-MS in individuals consuming pomegranate or nuts. The associations between basal CMR factors and the urine urolithin metabolomic signature were explored in 20 healthy normoweight individuals consuming walnuts (30 g/d), 49 healthy overweight-obese individuals ingesting pomegranate extract (450 mg/d) and 25 metabolic syndrome (MetS) patients consuming nuts (15 g-walnuts, 7.5 g-hazelnuts and 7.5 g-almonds/d). RESULTS: Correlations between CMR factors and urolithins were found in overweight-obese individuals. Urolithin-A (mostly present in UM-A) was positively correlated with apolipoprotein A-I (P ≤ 0.05) and intermediate-HDL-cholesterol (P ≤ 0.05) while urolithin-B and isourolithin-A (characteristic from UM-B) were positively correlated with total-cholesterol, LDL-cholesterol (P ≤ 0.001), apolipoprotein B (P ≤ 0.01), VLDL-cholesterol, IDL-cholesterol, oxidized-LDL and apolipoprotein B:apolipoprotein A-I ratio (P ≤ 0.05). In MetS patients, urolithin-A only correlated inversely with glucose (P ≤ 0.05). Statin-treated MetS patients with UM-A showed a lipid profile similar to that of healthy normoweight individuals while a poor response to lipid-lowering therapy was observed in MB patients. CONCLUSIONS: UMs are potential CMR biomarkers. Overweight-obese individuals with UM-B are at increased risk of cardiometabolic disease, whereas urolithin-A production could protect against CMR factors. Further research is warranted to explore these associations in larger cohorts and whether the effect of lipid-lowering drugs or ellagitannin-consumption on CMR biomarkers depends on individuals' UM. CLINICAL TRIAL REGISTRY NUMBERS AND WEBSITES: NCT01916239 (https://clinicaltrials.gov/ct2/show/NCT01916239) and ISRCTN36468613 (http://www.isrctn.com/ISRCTN36468613).


Asunto(s)
Cumarinas/metabolismo , Taninos Hidrolizables/metabolismo , Juglans/química , Lythraceae/química , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Peso Corporal , Enfermedades Cardiovasculares/metabolismo , Femenino , Frutas/química , Microbioma Gastrointestinal/fisiología , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Nueces/química , Sobrepeso/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/metabolismo , Factores de Riesgo
13.
Genome Announc ; 5(50)2017 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-29242216

RESUMEN

Gordonibacter urolithinfaciens DSM 27213T 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.

14.
Front Microbiol ; 8: 1521, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28824607

RESUMEN

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, both the ability of producing the final metabolites in this catabolism (urolithins A, B and isourolithin A) and the health benefits associated with ellagitannin consumption differ considerably among individuals depending on their gut microbiota composition. Three human urolithin metabotypes have been previously described, i.e., metabotype 0 (urolithin non-producers), metabotype A (production of urolithin A as unique final urolithin) and metabotype B (urolithin B and/or isourolithin A are produced besides urolithin A). Although production of some intermediary urolithins has been recently attributed to intestinal species from Eggerthellaceae family named Gordonibacter urolithinfaciens and Gordonibacter pamelaeae, the identification of the microorganisms responsible for the complete transformation of EA into the final urolithins, especially those related to metabotype B, are still unknown. In the present research we illustrate the isolation of urolithin-producing strains from human feces of a healthy adult and their ability to transform EA into different urolithin metabolites, including isourolithin A. The isolates belong to a new genus from Eggerthellaceae family. EA transformation and urolithin production arisen during the stationary phase of the growth of the bacteria under anaerobic conditions. The HPLC-DAD-MS analyses demonstrated the sequential appearance of 3,8,9,10-tetrahydroxy-urolithin (urolithin M6), 3,8,9-trihydroxy-urolithin (urolithin C) and 3,9-dihydroxy-urolithin (isourolithin A) while 3,8-dihydroxy-urolithin (urolithin A) and 3-hydroxy-urolithin (urolithin B) were not detected. For the first time isourolithin A production capacity of pure strains has been described. The biological activity attributed to urolithins A and B and isourolithin A (anti-inflammatory, anti-carcinogenic, cardioprotective, and neuroprotective properties) explains the relevance of identifying these urolithin-producing bacteria as potential novel probiotics with applications in the development of functional foods and nutraceuticals. Their human administration could improve the health benefits upon ellagitannin consumption, especially in metabotype 0 individuals. However, further research is necessary to probe well-established beneficial effects on the host and safety requirements before being considered among the next-generation probiotics.

15.
J Agric Food Chem ; 65(27): 5480-5493, 2017 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-28616977

RESUMEN

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 in vivo metabolic profiles for each metabotype. The study shows for the first time that microbial composition, metabolism of ellagitannins, and SCFA differ between metabotypes and along the large intestine. The assay also showed that pomegranate phenolics preserved intestinal cell integrity. Pomegranate polyphenols enhanced urolithin and propionate production, as well as Akkermansia and Gordonibacter prevalence with the highest effect in the descending colon. The system provides an insight into the mechanisms of pomegranate polyphenol gut microbiota metabolism and absorption through intestinal cells. The results obtained by the combined SHIME/Caco-2 cell system are consistent with previous human and animal studies and show that although urolithin metabolites are present along the gastrointestinal tract due to enterohepatic circulation, they are predominantly produced in the distal colon region.


Asunto(s)
Bacterias/aislamiento & purificación , Cumarinas/metabolismo , Microbioma Gastrointestinal , Tracto Gastrointestinal/metabolismo , Lythraceae/metabolismo , Extractos Vegetales/metabolismo , Polifenoles/metabolismo , Animales , Bacterias/metabolismo , Ácidos Grasos Volátiles/metabolismo , Tracto Gastrointestinal/microbiología , Humanos , Taninos Hidrolizables/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/microbiología
16.
Curr Opin Clin Nutr Metab Care ; 19(6): 471-476, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27490306

RESUMEN

PURPOSE OF REVIEW: Dietary (poly)phenolic compounds have received attention over the last 20 years as antioxidants with preventive properties against chronic diseases. However, the evidence of these effects in clinical trials is weak, mainly because of a considerable interindividual variability. Polyphenols bioavailability is low, and gut microbiota metabolize them into simpler metabolites. As gut microbiota vary among individuals, such interindividual variability should be considered as a moderating factor in clinical trials. In this review, we show evidence of interactions with gut microbiota that help understanding polyphenols' health effects. RECENT FINDINGS: Recent studies indicate that dietary polyphenols are relevant in the modulation of gut microbiota and that these microorganisms convert polyphenols into active and bioavailable metabolites; hence, variations in gut microbiota can affect polyphenol activity. SUMMARY: The results show that study participants' stratification by their polyphenol-metabolizing phenotypes would be necessary for clinical trials as specific metabotypes produce the bioactive metabolites responsible for the health effects. Metabotypes can also reflect the gut microbiota composition and metabolic status, and could be biomarkers of the potential polyphenol health effects mediated through gut microbiota.


Asunto(s)
Dieta , Microbioma Gastrointestinal/efectos de los fármacos , Polifenoles/administración & dosificación , Animales , Disbiosis/complicaciones , Disbiosis/prevención & control , Equol/metabolismo , Flavonoides/metabolismo , Microbioma Gastrointestinal/fisiología , Estado de Salud , Humanos , Microbiota/fisiología , Polifenoles/metabolismo
17.
Food Funct ; 7(4): 1769-74, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26597167

RESUMEN

We recently identified three metabotypes (0, A and B) that depend on the metabolic profile of urolithins produced from polyphenol ellagic acid (EA). The gut microbiota and Gordonibacter spp. recently were identified as species able to produce urolithins. A higher percentage of metabotype B was found in patients with metabolic syndrome or colorectal cancer in comparison with healthy individuals. The aim of the present study was to analyse differences in EA metabolism between healthy overweight-obese and normoweight individuals and evaluate the role of gut microbial composition including Gordonibacter. Although the three metabotypes were confirmed in both groups, metabotype B prevailed in overweight-obese (31%) versus normoweight (20%) individuals while metabotype A was higher in normoweight (70%) than the overweight-obese group (57%). This suggests that weight gain favours the growth of bacteria capable of producing urolithin B and/or isourolithin A with respect to urolithin A-producing bacteria. Gordonibacter spp. levels were not significantly different between normoweight and overweight-obese groups but higher Gordonibacter levels were found in metabotype A individuals than in those with metabotype B. Other bacterial species have been reported to show a much closer relationship to obesity and dysbiosis than Gordonibacter. However, Gordonibacter levels are negatively correlated with metabotype B, which prevails in metabolic syndrome and colorectal cancer. This is the first report that links overweight and obesity with an alteration in the catabolism of EA, and where the correlation of Gordonibacter to this alteration is shown. Future investigation of Gordonibacter and urolithin metabotypes as potential biomarkers or therapeutic targets of obesity-related diseases is warranted.


Asunto(s)
Bacterias/metabolismo , Ácido Elágico/metabolismo , Microbioma Gastrointestinal , Obesidad/metabolismo , Obesidad/microbiología , Sobrepeso/metabolismo , Sobrepeso/microbiología , Actinobacteria/genética , Actinobacteria/aislamiento & purificación , Actinobacteria/metabolismo , Adulto , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Biodiversidad , Cumarinas/química , Cumarinas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad
18.
J Agric Food Chem ; 62(28): 6535-8, 2014 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-24976365

RESUMEN

Three phenotypes for urolithin production after ellagitannin and ellagic acid intake are consistently observed in different human intervention trials. Subjects can be stratified into three urolithin-producing groups. "Phenotype A" produced only urolithin A conjugates, which included between 25 and 80% of the volunteers in the different trials. "Phenotype B" produced isourolithin A and/or urolithin B in addition to urolithin A, this being the second relevant group (10-50%). "Phenotype 0" (5-25%) was that in which these urolithins were not detected. The three phenotypes were observed independently of the volunteers' health status and demographic characteristics (age, gender, body mass index (BMI)) and of the amount or type of ellagitannin food source ingested (walnuts and other nuts, strawberries, raspberries, and other berries or pomegranates). Interestingly, a higher percentage of phenotype B was observed in those volunteers with chronic illness (metabolic syndrome or colorectal cancer) associated with gut microbial imbalance (dysbiosis). These urolithin phenotypes could show differences in the human gut microbiota and should be considered in intervention trials dealing with health benefits of ellagitannins or ellagic acid. Whether this phenotypic variation could be a biomarker related to differential health benefits or illness predisposition deserves further research.


Asunto(s)
Bacteriemia/metabolismo , Cumarinas/metabolismo , Ácido Elágico/metabolismo , Intestinos/microbiología , Adulto , Factores de Edad , Índice de Masa Corporal , Dieta , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Fenotipo
19.
Food Funct ; 5(8): 1779-84, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24909569

RESUMEN

Ellagitannin and ellagic acid metabolism to urolithins in the gut shows a large human interindividual variability and this has been associated with differences in the colon microbiota. In the present study we describe the isolation of one urolithin-producing strain from the human faeces of a healthy volunteer and the ellagic acid transformation to different urolithin metabolites by two species of intestinal bacteria. The isolate belongs to a new species described as Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter genus, Gordonibacter pamelaeae DSM 19378(T), was also demonstrated to produce urolithins. Both human intestinal bacteria grew similarly in the presence and absence of ellagic acid at 30 µM concentration. Ellagic acid catabolism and urolithin formation occurred during the stationary phase of the growth of the bacteria under anaerobic conditions. The HPLC-MS analyses showed the sequential production of pentahydroxy-urolithin (urolithin M-5), tetrahydroxy-urolithin (urolithin M-6) and trihydroxy-urolithin (urolithin C), while dihydroxy-urolithins (urolithin A and isourolithin A), and monohydroxy-urolithin (urolithin B) were not produced in pure cultures. Consequently, either other bacteria from the gut or the physiological conditions found in vivo are necessary for completing metabolism until the final urolithins (dihydroxy and monohydroxy urolithins) are produced. This is the first time that the urolithin production capacity of pure strains has been demonstrated. The identification of the urolithin-producing bacteria is a relevant outcome as urolithin implication in health (cardiovascular protection, anti-inflammatory and anticarcinogenic properties) has been supported by different bioassays and urolithins can be used in the development of functional foods and nutraceuticals. This study represents an initial work that opens interesting possibilities of describing enzymatic activities involved in urolithin production that can help in understanding both the human interindividual differences in polyphenol metabolism, the microbial pathways involved, and the role of polyphenols in human health. The presence of urolithin producing bacteria can indirectly affect the health benefits of ellagitannin consumption.


Asunto(s)
Actinobacteria/metabolismo , Colon/microbiología , Cumarinas/metabolismo , Ácido Elágico/metabolismo , Actinobacteria/clasificación , Actinobacteria/aislamiento & purificación , Adulto , Cromatografía Líquida de Alta Presión , Heces/microbiología , Femenino , Voluntarios Sanos , Humanos , Taninos Hidrolizables/metabolismo , Espectrometría de Masas , Microbiota , Polifenoles/metabolismo , Espectrometría de Masas en Tándem
20.
Int J Syst Evol Microbiol ; 64(Pt 7): 2346-2352, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24744017

RESUMEN

Urolithins are dibenzopyranone metabolites that exert anti-inflammatory activity in vivo and are produced by the gut microbiota from the dietary polyphenols ellagic acid (EA) and ellagitannins. However, the bacteria involved in this process remain unknown. We report here a novel bacterium, strain CEBAS 1/15P(T), capable of metabolizing EA to urolithins, that was isolated from healthy human faeces and characterized by determining phenotypic, biochemical and molecular methods. The strain was related to Gordonibacter pamelaeae 7-10-1-b(T), the type and only reported strain of the only species of the genus Gordonibacter, with about 97% 16S rRNA gene sequence similarity; they were both obligately anaerobic, non-spore-forming, Gram-stain-positive, short-rods/coccobacilli and metabolized only small numbers of carbon sources. L-Fucose, D-fructose, turanose, D-galacturonic acid and α-ketobutyric acid were metabolized by strain CEBAS 1/15P(T), while G. pamelaeae was negative for metabolism of these compounds. The whole-cell fatty acids consisted predominantly of saturated fatty acids (70%); strain CEBAS 1/15P(T) differed significantly from G. pamelaeae in the major fatty acid, which was C18 : 1ω9c, while anteiso-C15 : 0 was the major component for G. pamelaeae. The presence of a number of different fatty acid peaks, especially C19 : 0 cyclo and C18 : 1ω6c, was also indicative of distinct species. Six glycolipids (GL1-6) were recognized, while, in G. pamelaeae, only four glycolipids were described. On the basis of these data, the novel species Gordonibacter urolithinfaciens sp. nov. is described, with strain CEBAS 1/15P(T) ( = DSM 27213(T) = CCUG 64261(T)) as the type strain.


Asunto(s)
Actinobacteria/clasificación , Cumarinas/metabolismo , Tracto Gastrointestinal/microbiología , Filogenia , Actinobacteria/genética , Actinobacteria/aislamiento & purificación , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Ácidos Grasos/química , Heces/microbiología , Femenino , Glucolípidos/química , Humanos , Datos de Secuencia Molecular , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , España , Vitamina K 2/análogos & derivados , Vitamina K 2/química
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