GRUP DE RECERCA BIOMARCADORS I METABOLÒMICA NUTRICIONAL DELS ALIMENTS

Universitat de Barcelona (Barcelona)

Directora: Cristina Andrés Lacueva, Professora Titular del Departament de Nutrició i Bromatologia, Universitat de Barcelona

Adreça mail de contacte del grup de Recerca: candres@ub.edu
Telèfon de contacte: (+34) 934 03 48 40
Twitter: @NutriMetabolom
Web: http://www.nutrimetabolomics.com

Actualització fitxa tècnica del grup: juliol 2017

MEMBRES DEL GRUP INVESTIGADOR

Cristina Andres Lacueva; Professor Titular d’Universitat, Universitat de Barcelona
a/e: candres@ub.edu

Mireia Urpí Sardà, Investigador-Ramón y Cajal, Universitat de Barcelona
a/e: murpi@ub.edu

Rafael Llorach, Professor Lector, Universitat de Barcelona
a/e: rafallorach@ub.edu

Olga Jauregui, Técnico Superior en Química Analítica, PhD, Universitat de Barcelona
a/e: ojauregui@ccit.ub.edu

Nicola Kielland, Investigador posdoctoral_Project Manager, Universitat de Barcelona
a/e: nicola.kielland@gmail.com

Anna Marco Ramell, Investigador Postdoctoral-Juan de la Cierva formación, Universitat de Barcelona
a/e: anna.marco@ub.edu

Raúl Gonzalez Domingez, Investigador Postdoctoral-Juan de la Cierva formación, Universitat de Barcelona
a/e: raul.gonzalez@ub.edu

Patricia Casas Agustench, Investigador Postdoctoral projecte EU, Universitat de Barcelona
a/e: patricia.casas@ub.edu

Mar Garcia-Aloy, Investigador Postdoctoral projecte EU, Universitat de Barcelona
a/e: margarcia@ub.edu

Enrique Almanza Aguilera, Investigador predoctoral-CONACYT, Universitat de Barcelona
a/e: ealmanza@ub.edu

Magalí Palau Rodriguez, Investigador predoctoral-APIF-INSA, Universitat de Barcelona
a/e: palaumagali@ub.edu

Nicole Hidalgo Liberona, Investigador predoctoral projecte EU, Universitat de Barcelona
a/e: n.hidalgoliberona@ub.edu

ACTIVITATS I CAPACITATS DEL GRUP DE RECERCA

El grup d’investigació en Biomarcadors i Metabolòmica Nutricional i dels Aliments pertany al Departament de Nutrició, Ciència dels Aliments i Gastronomia de la Universitat de Barcelona, CIBER de Fragilitat i Envelliment saludable (CIBERFES), a la Xarxa de Food-Omics i INSA-UB. Focalitza la seva activitat en la investigació de biomarcadors de consum, d’efecte i de risc de malaltia en estudis nutricionals i epidemiològics mitjançant l’estudi de perfils metabolòmic.
El nostre objectiu principal és la identificació de biomarcadors nutricionals associats a patrons dietètics que permetin l’estudi de metabotips i fenotips associats principalment a risc de malaltia i encaminat a un envelliments saludable.
La seva activitat de recerca principal es centra en estudis de metabolòmica, una tècnica indispensable en la biologia de sistemes. Les línies de recerca del grup, que col·labora activament amb equips internacionals, inclouen estudiar nous biomarcadors robustos, sensibles i fiables, basats en la seva Biodisponibilitat, activitat i relació amb la ingesta d’alguns aliments (marcadors de consum), i en la comprensió de la seva associació amb l’obesitat, l’envelliment i la reducció del risc cardiovascular (marcadors d’efecte). La metodologia utilitzada es basa en estudis dirigits i / o no dirigits mitjançant una aproximació metabolòmica (LC-MS / MS, Orbitrap, RMN).

LÍNIES DE RECERCA

Línia: Desenvolupament de taules de composició d’aliments en compostos bioactius per a l’Estudi de patrons Dietètics i caracterització Nutricional de la Dieta
Investigador principal: Patricia Casas, Cristina Andres-Lacueva

Línia: Desenvolupament de base de dades de consum de fitoquímics i biomarcadors de risc de malaltia. Metabolómica per a la detecció precós de marcadors de malaltia. Fisiopatologia de la síndrome de la fragilitat.
Investigador principal: Mireia Urpí-Sardà, Cristina Andres-Lacueva

Línia: Estandardització de protocols d’anàlisis de metabolòmica i perfils metabolòmics en mostres biològiques. Metodologia dirigida i no dirigida per NMR i LC-MS/MS.
Investigador principal: Raul González, Olga Jáuregui, Cristina Andres-Lacueva

Línia: Estudi de biomarcadors nutricionals associats a patrons dietètics, metabotips i fenotips de malaltia. Caracterització de Metabotips per a l’avaluació de la resposta a diferents patrons dietètics. Estudi de Responedors i no responedors i la interindividualitat. Paper de l’alimentació en la relació hoste-microbiota intestinal.
Investigador principal: Cristina Andres-Lacueva, Mireia Urpí-Sardà

Línia: Desenvolupament d’eines bioinformàtiques per la interpretació i visualització de resultats metabolòmics
Investigador principal: Anna Marco, Cristina Andres-Lacueva

Línia: Desenvolupament d’eines docents per a l’estudi del metaboloma dels aliments i la seva aplicació en salut.
Investigador Principal: Rafael Llorach

MILLORS PUBLICACIONS DEL GRUP (2015-2017)

Madrid-Gambin F, Llorach R, Vázquez-Fresno R, Urpi-Sarda M, Almanza-Aguilera E, Garcia-Aloy M, Estruch R, Corella D, Andres-Lacueva C.
Urinary 1H Nuclear Magnetic Resonance Metabolomic Fingerprinting Reveals Biomarkers of Pulse Consumption Related to Energy-Metabolism Modulation in a Subcohort from the PREDIMED study.
J Proteome Res. 2017 6(4):1483-1491.
PMID: 28067528

Abstract: Little is known about the metabolome fingerprint of pulse consumption. The study of robust and accurate biomarkers for pulse dietary assessment has great value for nutritional epidemiology regarding health benefits and their mechanisms. To characterize the fingerprinting of dietary pulses (chickpeas, lentils, and beans), spot urine samples from a subcohort from the PREDIMED study were stratified using a validated food frequency questionnaire. Urine samples of nonpulse consumers (≤4 g/day of pulse intake) and habitual pulse consumers (≥25 g/day of pulse intake) were analyzed using a 1H nuclear magnetic resonance (NMR) metabolomics approach combined with multi- and univariate data analysis. Pulse consumption showed differences through 16 metabolites coming from (i) choline metabolism, (ii) protein-related compounds, and (iii) energy metabolism (including lower urinary glucose). Stepwise logistic regression analysis was applied to design a combined model of pulse exposure, which resulted in glutamine, dimethylamine, and 3-methylhistidine. This model was evaluated by a receiver operating characteristic curve (AUC > 90% in both training and validation sets). The application of NMR-based metabolomics to reported pulse exposure highlighted new candidates for biomarkers of pulse consumption and the impact on energy metabolism, generating new hypotheses on energy modulation. Further intervention studies will confirm these findings.

Tulipani, S, Mora-Cubillos X, Jáuregui O, Llorach R, García-Fuentes E, Tinahones F, Andres-Lacueva C.
New and Vintage Solutions To Enhance the Plasma Metabolome Coverage by LC-ESI-MS Untargeted Metabolomics: The Not-So-Simple Process of Method Performance Evaluation.
Anal Chem. 2015, 3; 87(5):2639-2647.
PMID: 25642801

Abstract: Although LC-MS untargeted metabolomics continues to expand into exiting research domains, methodological issues have not been solved yet by the definition of unbiased, standardized and globally accepted analytical protocols. In the present study, the response of the plasma metabolome coverage to specific methodological choices of the sample preparation (two SPE technologies, three sample-to-solvent dilution ratios) and the LC-ESI-MS data acquisition steps of the metabolomics workflow (four RP columns, four elution solvent combinations, two solvent quality grades, postcolumn modification of the mobile phase) was investigated in a pragmatic and decision tree-like performance evaluation strategy. Quality control samples, reference plasma and human plasma from a real nutrimetabolomic study were used for intermethod comparisons. Uni- and multivariate data analysis approaches were independently applied. The highest method performance was obtained by combining the plasma hybrid extraction with the highest solvent proportion during sample preparation, the use of a RP column compatible with 100% aqueous polar phase (Atlantis T3), and the ESI enhancement by using UHPLC-MS purity grade methanol as both organic phase and postcolumn modifier. Results led to the following considerations: submit plasma samples to hybrid extraction for removal of interfering components to minimize the major sample-dependent matrix effects; avoid solvent evaporation following sample extraction if loss in detection and peak shape distortion of early eluting metabolites are not noticed; opt for a RP column for superior retention of highly polar species when analysis fractionation is not feasible; use ultrahigh quality grade solvents and “vintage” analytical tricks such as postcolumn organic enrichment of the mobile phase to enhance ESI efficiency. The final proposed protocol offers an example of how novel and old-fashioned analytical solutions may fruitfully cohabit in untargeted metabolomics protocols.

Rabassa M, Zamora-Ros R, Urpi-Sarda M, Bandinelli S, Ferrucci L, Andres-Lacueva C, Cherubini A.
Association of habitual dietary resveratrol exposure with the development of frailty in older age: the Invecchiare in Chianti study.
Am J Clin Nutr. 2015; 102(6):1534-1542.
PMID: 26490492

BACKGROUND: Resveratrol may play a protective role against the frailty syndrome (FS) because of its antioxidant and anti-inflammatory properties.
OBJECTIVE: We prospectively evaluated the association between habitual dietary resveratrol exposure and the development of FS after 3-, 6-, and 9-y follow-up periods in a community-dwelling older population.
DESIGN: We conducted a longitudinal analysis with the use of data from 769 participants aged ≥65 y from the Invecchiare in Chianti (Aging in Chianti) study. Total dietary resveratrol (TDR) intake was estimated at baseline with the use of a validated food-frequency questionnaire, which was developed to assess participants’ usual food intakes over the previous year, and an ad hoc resveratrol database. Total urinary resveratrol (TUR) was analyzed with the use of liquid chromatography-tandem mass spectrometry with a previous solid-phase extraction at baseline. The combination of both measures [total dietary resveratrol plus total urinary resveratrol (TDR+TUR)] was computed with the use of the Howe’s method. FS was assessed at baseline and at 3-, 6-, and 9-y of follow-up and was defined as the presence of ≥3 of the following 5 criteria: shrinking, exhaustion, sedentariness, slowness, and weakness.
RESULTS: TDR+TUR concentrations were inversely associated with FS risk over 3-y of follow-up (OR for comparison of extreme tertiles: 0.11; 95% CI: 0.03, 0.45; P-trend = 0.002) but not after 6- and 9-y of follow-up in multinomial logistic regression models adjusted for baseline frailty status and potential confounders. These results did not differ when analyses were further adjusted for inflammatory markers.
CONCLUSION: Higher habitual dietary resveratrol exposure was associated with lower risk of older community dwellers developing FS during the first 3 y of follow-up but not after longer follow-up periods.

Semba RD, Ferrucci L, Bartali B, Urpí-Sarda M, Zamora-Ros R, Sun K, Cherubini A, Bandinelli S, Andres-Lacueva C.
Resveratrol levels All-Cause Mortality in Older Community-Dwelling Adults.
JAMA Intern Med. 2014; 174(7):1077-1084.
PMID: 24819981

IMPORTANCE: Resveratrol, a polyphenol found in grapes, red wine, chocolate, and certain berries and roots, is considered to have antioxidant, anti-inflammatory, and anticancer effects in humans and is related to longevity in some lower organisms.
OBJECTIVE: To determine whether resveratrol levels achieved with diet are associated with inflammation, cancer, cardiovascular disease, and mortality in humans.
DESIGN: Prospective cohort study, the Invecchiare in Chianti (InCHIANTI) Study (“Aging in the Chianti Region”), 1998 to 2009 conducted in 2 villages in the Chianti area in a population-based sample of 783 community-dwelling men and women 65 years or older.
EXPOSURES: Twenty-four-hour urinary resveratrol metabolites.
MAIN OUTCOMES AND MEASURES: Primary outcome measure was all-cause mortality. Secondary outcomes were markers of inflammation (serum C-reactive protein [CRP], interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]) and prevalent and incident cancer and cardiovascular disease.
RESULTS: Mean (95% CI) log total urinary resveratrol metabolite concentrations were 7.08 (6.69-7.48) nmol/g of creatinine. During 9 years of follow-up, 268 (34.3%) of the participants died. From the lowest to the highest quartile of baseline total urinary resveratrol metabolites, the proportion of participants who died from all causes was 34.4%, 31.6%, 33.5%, and 37.4%, respectively (P = .67). Participants in the lowest quartile had a hazards ratio for mortality of 0.80 (95% CI, 0.54-1.17) compared with those in the highest quartile of total urinary resveratrol in a multivariable Cox proportional hazards model that adjusted for potential confounders. Resveratrol levels were not significantly associated with serum CRP, IL-6, IL-1β, TNF, prevalent or incident cardiovascular disease, or cancer.
CONCLUSIONS AND RELEVANCE: In older community-dwelling adults, total urinary resveratrol metabolite concentration was not associated with inflammatory markers, cardiovascular disease, or cancer or predictive of all-cause mortality. Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study.

Garcia-Aloy M, Rabassa M, Casas-Agustench P, Hidalgo-Liberona N, Llorach R, Andres-Lacueva C.
Novel strategies for improving dietary exposure assessment: Multiple-data fusion is a more accurate measure than the traditional single-biomarker approach
Trends Food Sci Technol. 2017; [IN PRESS]

INSTITUCIONS QUE RECONEIXEN AL GRUP DE RECERCA

UB: Universitat de Barcelona

CIBERFES: Centros de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable, Institut de Salut Carles III

INSA: Institut de Nutrició i Seguretat Alimentària de la UB

XARTA: Xarxa de Referència en Tecnologia d’Aliments

Grup de Recerca Consolidat de l’AGAUR (2014 SGR 1566)