[spa] Los biomarcadores nutricionales proporcionan una medida precisa y objetiva de la exposición dietética (biomarcadores de ingesta) y de su impacto en el individuo (biomarcadores de efecto), que unidos a las medidas tradicionales de consumo de alimentos pueden mejorar la medida de la exposición dietética y permitir la formulación de nuevas hipótesis sobre el impacto de la dieta en la salud. Esta Tesis Doctoral se enmarca dentro del consorcio “Food Biomarker Alliance” (FOODBALL), el cual propone llevar a cabo el estudio profundo de biomarcadores nutricionales. La presente Tesis Doctoral tiene como objetivo principal contribuir en el descubrimiento de biomarcadores nutricionales a través del análisis del perfil metabolómico asociado al consumo de legumbres y de café en muestras de orina y/o suero/plasma mediante Resonancia Magnética Nuclear (RMN), en estudios nutricionales con diferentes diseños. Para la evaluación del metaboloma asociado a la ingesta de legumbres (concretamente lentejas, garbanzos y alubias) se realizaron dos estudios: uno de intervención y uno observacional. En el estudio de intervención con individuos sanos, el perfil metabolómico urinario se caracterizó por estar asociado a metabolitos provenientes del “food metabolome” (trigonelina, dimetilglicina, 3-metilhistidina, trimetilamina, y lisina); y a metabolitos endógenos (mayores niveles de aminoácidos ramificados, glutamina, y ácido xanturénico; y menores niveles de glucosa). El análisis del metaboloma sérico reveló una menor cantidad de metabolitos significativos, mayormente endógenos (asparagina, histidina, dimetilglicina, lisina, 3-hidroxiisovalerato, 2-hidroxibutirato y glucosa). Los principales candidatos a biomarcadores urinarios fueron adicionalmente explorados a través de muestras biológicas recogidas hasta 48 h tras la ingesta de los alimentos. Para el estudio observacional de la huella metabolómica urinaria asociada con el consumo de legumbres, se estratificaron los sujetos según el consumo reportado mediante un cuestionario de frecuencia de consumo de alimentos. La exposición a legumbres se asoció con metabolitos provenientes del metabolismo de la colina, de compuestos relacionados con el metabolismo de los aminoácidos, y con el metabolismo energético. Con el objetivo de mejorar la capacidad predictiva del consumo de legumbres, se diseñó un modelo combinado de exposición que incluyó glutamina, dimetilamina y 3-metilhistidina. El modelo fue evaluado por una curva característica de funcionamiento del receptor (ROC) exhibiendo mayor área bajo la curva (>90%) en comparación con los modelos individuales (, [eng] Nutritional biomarkers provide a more accurate and objective measure of dietary exposure (biomarkers of intake) and their impact on the metabolism (biomarkers of effect) than traditional measures of food consumption. The main aim of this PhD is to contribute to the discovery of nutritional biomarkers by analyzing the metabolomic fingerprint associated with the consumption of pulses and coffee using Nuclear Magnetic Resonance (NMR) through nutritional studies with different designs. To investigate the metabolomic fingerprint associated with the dietary pulses intake (specifically lentils, chickpeas and beans), an intervention study was carried out in healthy individuals. The main candidates for urinary biomarkers (trigonelline, dimethylglycine, 3-methylhistidine, trimethylamine, and lysine) were further explored up to 48 h after food intake. In an observational study, a free-living population was stratified according to the reported consumption of pulses by a food frequency questionnaire. The exposure to pulses was associated with metabolites derived from the metabolism of choline and amino acids, as well as with energy metabolism. A multi-metabolite biomarker model was designed including glutamine, dimethylamine and 3-methylhistidine and positively evaluated by a receiver operating characteristic curve (ROC). The metabolites from the intervention study replicated in the observational study were dimethylglycine, 3-methylhistidine and trimethylamine as a precursor of trimethylamine-N-oxide (food metabolome); and glutamine, branched-chain amino acids, and lower glucose (endogenous metabolites). Therefore, these metabolites could be good candidates for nutritional biomarkers of pulses. Concerning the metabolomic study after the intake of a coffee with high content of bioactive compounds, the acute consumption indicated a higher urinary excretion of 2-furoylglycine and compounds of Krebs cycle. Sustained consumption of coffee exhibited an increase in compounds derived from microbial activity such as hippuric, 3-(3-hydroxyphenyl)-3-hydroxypropionic and 3-hydroxyhippuric acids. Trigonelline was found in the urine after both acute and sustained consumption of coffee. In both intervention studies (with legumes and coffee) the metabolic profile of the food was studied indicating certain precursors of compounds from the food metabolome. This Thesis presents different approaches through intervention and observational studies for the discovery of nutritional biomarkers of pulses and coffee through an untargeted metabolomic strategy using NMR.