Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Orientador: Flavia Maria Neto / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-21T08:25:23Z (GMT). No. of bitstreams: 1 Franca_CeliadeJesus_M.pdf: 1711635 bytes, checksum: 8b68d7bd0f495d93e2c2949a9229045c (MD5) Previous issue date: 2012 / Resumo: Estudos indicam que cerca de 2,5% dos recém-nascidos sofrem reações de hipersensibilidade ao leite bovino. Os principais componentes alergênicos do soro do leite bovino são as proteínas ß-Lactoglobulina (ß-Lg) e a-Lactoalbumina (a-La). A enzima transglutaminase (TG) tem sido utilizada para modificar as proteínas do soro do leite, podendo reduzir o seu potencial antigênico. O objetivo desse trabalho foi estudar o efeito do pH e relação enzima substrato (E:S) na polimerização do Isolado proteico do soro do leite (IPS) com a TG em diferentes condições utilizando a Metodologia de Superfície de Resposta, e avaliar a redução do potencial antigênico das proteínas pela suscetibilidade dos produtos obtidos à digestão com pepsina. O estudo da polimerização do IPS foi realizado por meio de experimentos fatoriais 22, nos quais as variáveis independentes foram a relação enzima:substrato (E:S) (15,7 ¿ 56,9 U TG /g de proteína) e pH (5,0 ¿ 8,4). A variável dependente foi a polimerização das amostras avaliada pela concentração relativa das proteínas ß-Lg ([ß-Lg]) e a-La ([a-La]) após a reação de polimerização, medida por densitometria do gel. Para o estudo da polimerização, foram realizados dois DCCR(Delineamento Composto Central Rotacional): DCCR 1 no qual foi utilizado o IPS sem qualquer tratamento e DCCR 2 no qual foi utilizado o IPS tratado termicamente. Para condição do DCCR 2, foi realizado um experimento preliminar afim de obter as melhores condições de tempo e temperatura de polimerização pela TG. A caracterização das amostras de IPS polimerizado foi realizada por eletroforese (SDS-PAGE). As amostras que apresentaram a menor [ß-Lg] foram empregadas para o estudo de resistência à pepsina, foram utilizados dois modelos de simulação da digestão gástrica: o adulto (182 U de pepsina/g de proteína, pH 2,0) e o infantil (23 U de pepsina/g de proteína, pH 4,0) seguida por caracterização por eletroforese (SDS-PAGE). A avaliação in vitro da antigenicidade dos digeridos gástricos foi realizada por ELISA, utilizando soro de camundongos BALB/c sensibilizados com ß-Lg na forma nativa. A polimerização do IPS pela TG foi mais eficiente quando a proteína foi previamente desnaturada por tratamento térmico. No DCCR 1 ocorreu maior polimerização da a-La do que da ß-Lg, indicando que esta proteína reage facilmente com a TG, mesmo sem tratamento térmico prévio. A digestão in vitro do IPS foi mais eficiente nas condições fisiológicas simulando o modelo adulto do que o infantil. Em ambos os modelos, a amostra tratada termicamente e polimerizada com TG (IPS/TT-TG) foi mais susceptível à pepsina e também foi a que apresentou a menor resposta frente IgE anti- ß-Lg. A diminuição moderada do potencial alergênico após os tratamentos realizados sugerem que houve modificação e ou ocultação de epítopos da estrutura da proteína / Abstract: Studies indicate that about 2.5% of newborns suffer from hypersensitivity reactions to cow¿s milk. The main allergenic components of bovine whey proteins are ß-lactoglobulin (ß-Lg) and a-lactalbumin (a-La). The enzyme transglutaminase (TG) has been used for modifying whey proteins, and may reduce their antigenic potential. The present work aimed at studying the effect of pH and enzyme substrate (E:S) on the polymerization of the IPS with TG under different conditions using Response Surface Methodology, and evaluate the reduction of potential of the antigenic proteins using the susceptibility of products to pepsin digestion. The study of the IPS polymerization was performed by factorial experiments 22, in which the independent variables were enzyme: substrate ratio (E: S) (15.7 to 56.9 U TG / g of protein (U g-1) ) and pH (5.0 - 8.4). The dependent variable was polymerization of the samples evaluated by the relative concentration of the ß-Lg ([ß-Lg]) and a-La ([La-a]) after the polymerization reaction, evaluated by densitometry of the gel. To study the polymerization, two CRCD (Central Rotatable Composite Design) were performed: CRCD 1 in which untreated WPI was used and CRCD 2 in which WPI denatured by heat treatment was used. The characterization of the samples was performed by SDS-PAGE. The evaluation of the polymerization was achieved by the relative concentration of the proteins ß-Lg ([ß-Lg]) and a-La (([a-La]) after polymerization, determined by densitometry. The samples with the lowest [ß-Lg] were chosen for the study of resistance to pepsin using two simulation models of gastric digestion, the adult (182 U pepsin / g of protein and pH 2.0) and infant (23 U pepsin / g of protein, pH 4.0). The resistance of the proteins to the action of pepsin was evaluated by SDS-PAGE. Evaluation of the antigenicity of the samples before and after gastric digestion was performed by ELISA using sera from BALB/c mice sensitized with ß-Lg in its native form. Between the two designs carried out for the polymerization of WPI by TG, the one in which the WPI has previously been denatured by heat treatment was more effective. The in vitro digestion of WPI was more efficient under conditions simulating the physiological adult model than the infant model. In both models the sample which was heat treated and subsequently polymerized by TG was more susceptible to pepsin, and showed the lowest anti-IgE response against ß-Lg, indicating that the allergenic potential was decreased after treatment. These results suggested that there was a modified and/or hidden of the epitopes / Mestrado / Nutrição Experimental e Aplicada à Tecnologia de Alimentos / Mestra em Alimentos e Nutrição

Circa l’1% della popolazione mondiale è colpita da celiachia. I celiaci sono costretti a seguire una dieta priva di glutine e molto spesso quest’ultima risulta essere sbilanciata e/o carente in molti nutrienti. Recentemente, l’uso di matrici alternative al frumento, come pseudocereali, legumi e cultivar di riso pigmentate sta riscuotendo grande interesse a causa del loro elevato quantitativo di composti bioattivi (polifenoli). Quindi, considerando l’importanza attuale dei polifenoli sia nella formulazione tecnologica che nella promozione di aspetti salutistici degli alimenti senza glutine, lo scopo di questa tesi è stata basata su: 1) profilazione dei polifenoli in matrici prive di glutine (farine non di frumento, legumi, pseudocereali e frutta secca) e loro proprietà antiossidanti in vitro; 2) valutazione dell’impatto di trattamenti termici e di fermentazioni microbiche sul profilo fenolico di queste matrici prive di glutine; 3) valutazione del ruolo dei polifenoli come inibitori degli enzimi amilolitici; e 4) valutazione del destino dei polifenoli caratterizzanti alimenti senza glutine durante processi in vitro simulanti digestione gastrointestinale e fermentazione fecale. I polifenoli sono stati analizzati sfruttando tecniche di metabolomica mirata/non-mirata. / Around 1% of world population is affected by coeliac disease. Coeliac people are constrained to follow a strict gluten free (GF) diet and very often this latter is unbalanced and lacks in many nutrients. In the last years, the exploitation of alternative crops or underutilized species, such as pseudocereals, legumes and pigmented cereal cultivars, is gaining interest because of their amount and profile of bioactive compounds, such as polyphenols. Therefore, considering the actual importance of polyphenols for both the formulation of GF foods and their health-promoting properties, the current PhD thesis was based on: 1) the profiling of polyphenols in GF raw materials (such as non-wheat flours, legumes, pseudocereals and nuts) and their in vitro antioxidant activities; 2) the evaluation of the impact of different heat treatments and microbial fermentations on the phenolic profile of GF raw materials; 3) the investigation of polyphenols in GF foods as inhibitors of digestive enzymes; and 4) the assessment of the fate of polyphenols characterizing GF foods during simulated in vitro gastrointestinal and fermentation processes. Polyphenols were analysed by means of targeted/untargeted metabolomics-based approaches (i.e., high resolution chromatography and mass spectrometry platforms).

Les Escherichia coli entérohémorragiques (EHEC) sont des pathogènes majeurs pour l’homme responsables de toxi-infections alimentaires pouvant évoluer vers des complications potentiellement mortelles. La pathogénicité de ces souches est essentiellement due à la production de Shiga-toxines (Stx), même si d’autres facteurs semblent jouer un rôle important dans la virulence, comme des facteurs d’adhésion. La survie et la régulation des facteurs de virulence des EHEC dans l’environnement digestif humain sont des facteurs clés dans la pathogénicité bactérienne, mais restent à ce jour mal décrits, essentiellement en raison d’un manque de modèles d’étude adaptés. De plus, l’absence de traitement spécifique a conduit à s’intéresser à des moyens préventifs et/ou curatifs alternatifs, comme l’utilisation de probiotiques. L’objectif de ce travail de thèse est (i) de mieux comprendre le comportement de la souche de référence EHEC O157:H7 EDL933 dans l’environnement digestif humain simulé, et en particulier ses interactions avec le microbiote résident et l’épithélium intestinal, et (ii) d’évaluer l’effet antagoniste d’une souche de levure probiotique vis-à-vis de la survie, la virulence et l’interaction du pathogène avec l’épithélium intestinal, à l’aide d’approches in vitro et in vivo complémentaires. En modèles digestifs in vitro, la souche EHEC survit dans l’estomac, voire se multiplie dans les parties distales de l’intestin grêle, alors qu’elle ne se maintient pas dans l’environnement colique. Les gènes de virulence codant les Stx et des adhésines majeurs (intimine et « Long Polar Fimbriae » ou Lpf) sont surexprimés dès les parties hautes du tractus digestifs, et ce, même en absence de cellules épithéliales. Les conditions rencontrées dans le tractus digestif supérieur de l’enfant, comparativement à celui de l’adulte, conduisent à une survie et un niveau d’expression des gènes codant les Stx et les Lpf plus élevés chez l’enfant, ce qui peut contribuer à expliquer la grande sensibilité de cette population aux infections à EHEC. Enfin, les Lpf semblent jouent un rôle clé dans le ciblage spécifique des cellules M et le tropisme des EHEC pour les plaques de Peyer, et ce, à la fois in vitro (cellules M en culture) et in vivo (anses iléales murines). Même si elle ne modifie pas la survie du pathogène dans l’environnement colique, la levure probiotique S. cerevisiae CNCM I-3856 a montré des propriétés antagonistes intéressantes vis-à-vis d’EHEC O157:H7 en (i) modulant favorablement l’activité fermentaire du microbiote intestinal, (ii) diminuant significativement l’expression des gènes codant les Stx et (iii) inhibant la translocation bactérienne au travers des plaques de Peyer et les lésions hémorragiques associées. Par ailleurs, l’effet du pathogène et des probiotiques sur le microbiote colique est individu dépendant, confortant l’hypothèse que des facteurs associés à l’hôte, comme le microbiote, pourraient conditionner l’évolution clinique des infections à EHEC et l’efficacité d’une stratégie probiotique.Ce travail de thèse contribue à une meilleure compréhension du comportement des EHEC dans l’environnement digestif humain et confirme l’intérêt d’une stratégie probiotique dans la lutte contre le pathogène. Une étude plus approfondie du transcriptome du pathogène dans l’environnement digestif et une analyse par des méthodes haut débit du microbiote intestinal permettraient de continuer à mieux décrire la physiopathologie des infections à EHEC et comprendre les mécanismes associés à l’effet antagoniste des probiotiques. / The enterohemorrhagic Escherichia coli (EHEC) are major zoonotic pathogens responsible for food-borne infectionwhich leads to life-threatening complications in humans. The main virulence determinant of EHEC is the production of Shigatoxins (Stx), even if other factors seem to play an important role in virulence, such as adhesion factors. Survival and virulenceof EHEC strains in the human digestive environment are a key factor in bacterial pathogenesis but remains unclear owing tolack of relevant model. Moreover, no specific treatment has led to interest in preventative and / or curative alternatives, suchas using probiotics. The objective of this study is to better understand the behavior of the reference strain EHEC O157:H7EDL933 in the entire digestive tract, and in particular its interaction with the resident microbiota and the intestinal epithelium,and to evaluate the antagonistic effect of the probiotic yeast, Saccharomyces cerevisiae CNCM I-3856, using in vitro and in vivo complementary approaches.In vitro, bacterial mortality was noticed in the stomach, whereas bacterial growth resumption was observed in thedistal parts of the small intestine and the pathogen was not able to maintain in the human colonic conditions. Virulence genesencoding Stx and adhesins (intimin and “Long polar fimbriae”) are upregulated in the upper parts of the digestive tract. A ten-time higher amount of cells was found in the ileal effluents of infant compared to adult. stx genes were over-expressed (up to25-fold) in infant conditions compared to the adult ones. This results show that differences in digestive physicochemicalparameters of the upper gastrointestinal tract may partially explain why infants are more susceptible to EHEC infection thanadults. And finally, Lpf seem to play a key role in the interactions of EHEC with murine Peyer’s patches and are needed for anactive translocation of the pathogen across M cells, and both in vitro (M cells culture) and in vivo (murine ileal loops).S. cerevisiae had not effect on EHEC survival in the colonic environment but (i) favorably influenced gut microbiotaactivity through beneficial modulation of short chain fatty acid production, (ii) leading to significantly decrease stx expressionand (iii) significantly reduced EHEC translocation through M cells and inhibited in vivo interactions of the pathogen withPeyer’s patches and the associated hemorrhagic lesions. Probiotic had donor-dependent effect on the gut microbiota strengthenthe hypothesis that host-associated factors such as microbiota could influence the clinical evolution of EHEC infection and theeffectiveness of a probiotic strategy.This work contributes to a better understanding of the behavior of EHEC in the human digestive environment andconfirms the interest of probiotic strategy in controlling EHEC infections. Further transcriptome studies are warranted for thepathogen in the human digestive environment, with or without probiotics for the better understanding of the pathophysiologyof EHEC and so on the mechanisms involved in the antagonistic effect of probiotics.

Tesis por compendio / [ES] Debido a la creciente importancia de la dieta en el manejo de la salud, sigue habiendo un gran interés en desentrañar como se procesan los alimentos en el sistema digestivo humano. La estructura de los alimentos puede influir significativamente en su procesamiento, afectando al rendimiento durante la alimentación y la digestión. Específicamente, la digestión de alimentos a base de carbohidratos requiere una mayor comprensión debido a su contribución a los niveles de glucosa en sangre. El conocimiento de la cinética de digestión del almidón contribuirá a diseñar alimentos a medida para controlar los niveles de glucosa posprandial. El objetivo de esta tesis doctoral fue adquirir una mejor comprensión del impacto de la microestructura en la digestión del almidón y cómo las enzimas digestivas podrían ser moduladas por compuestos fenólicos. Con ese propósito, se evaluó el papel de la estructura del pan en la masticación in vivo y la digestión in vitro. Posteriormente, se produjeron geles de almidón de diferentes fuentes y se digirieron en un sistema de digestión oro-gastro-intestinal in vitro para analizar el impacto de la microestructura del gel. Después de los estudios de microestructura en geles de almidón y pan, se exploraron diferentes ácidos fenólicos o extractos polifenólicos de algas como inhibidores de enzimas digestivas de almidón, y se evaluó la participación de la microestructura del gel de almidón en la digestión enzimática. La masticación y la textura del bolo de panes tostados de trigo se vio afectada por su diferente estructura, a pesar de que no se observaron diferencias en la percepción sensorial. El proceso de panificación también ofreció la posibilidad de modificar la estructura del pan. De hecho, la variación de la forma de la masa dio lugar a panes con diferentes propiedades estructurales y texturales de la miga. La digestión de los panes con diferente estructura de miga confirmó que se disgregaban de manera diferente, produciendo variaciones en la posterior digestibilidad del almidón. Una vez que se estableció la importancia de la microestructura de la miga en la digestión del almidón, se cambió el enfoque para enlazar la microestructura de los geles de almidón con su digestión in vitro. Los geles obtenidos con almidones de distintas fuentes botánicas mostraron diferente digestibilidad, lo que se relacionó con su microestructura, pero también con su contenido de amilosa. Considerando la acción de las enzimas digestivas (α-amilasa y α-glucosidasa) sobre la hidrólisis del almidón, se estudiaron diferentes compuestos fenólicos para comprender las interacciones entre los compuestos fenólicos y las enzimas o sustratos. La forma más eficaz de inhibir las enzimas era incubarlas con ácidos fenólicos. Se necesitó una mayor concentración del inhibidor cuando los compuestos fenólicos interactuaban previamente con el sustrato, debido a su retención dentro del gel de almidón. La estructura química de los ácidos fenólicos controlaba la inhibición de la enzima. Asimismo, los extractos fenólicos complejos, como los extraídos de las algas A. nodosum, podrían utilizarse para inhibir las enzimas digestivas, mostrando mayor efecto inhibidor cuando fueron previamente incubados con la enzima, debido a la existencia de complejos carbohidrato-polifenoles con sus diferentes capacidades inhibitorias. Además, los ácidos fenólicos afectaron las propiedades de pegado y, por lo tanto, a la estructura y textura de geles de almidón. Sin embargo, esos cambios no fueron suficientes para controlar la hidrólisis enzimática del almidón, que estaba relacionada con la estructura química de los ácidos fenólicos y sus propiedades. En general, la microestructura de la miga o del gel puede limitar la accesibilidad de las enzimas digestivas, lo que reduciría la hidrólisis del almidón. Además, la inclusión de ácidos fenólicos en alimentos a base de almidón podría ser la alternativa para reducir el grado de digestión del almidón al inhibir estas enzimas. / [CA] A causa de la creixent importància de la dieta en el maneig de la salut, segueix sent de gran interès desentranyar com es processen els aliments en el sistema digestiu humà. L'estructura dels aliments pot influir significativament en el processament dels aliments, afectant al seu rendiment durant l'alimentació i la digestió. Específicament, la digestió d'aliments a base de carbohidrats requereix una major comprensió a conseqüència de la seua contribució als nivells de glucosa en sang. El coneixement de la cinètica de la digestió del midó contribuirà a dissenyar aliments a mesura per controlar els nivells de glucosa postprandial. L'objectiu d'aquesta tesi doctoral va ser adquirir una millor comprensió de l'impacte de la microestructura en la digestió del midó i com els enzims digestius podrien ser modulats per l'ús de compostos fenòlics. Amb aquest propòsit, es va avaluar el paper de l'estructura del pa en la masticació in vivo i la digestió in vitro. Posteriorment, es van produir gels de midó de diferents fonts i es van digerir en un sistema de digestió oro-gastrointestinal in vitro per analitzar l'impacte de la microestructura del gel. Després dels estudis de microestructura en gels de midó i pa, es van explorar diferents àcids fenòlics o extractes polifenòlics d'algues com inhibidors dels enzims digestius del midó, i es va avaluar la participació de la microestructura del gel de midó en la digestió enzimàtica. La masticació i la textura de la bitla de pans torrats de blat es va veure afectada per les seues diferencies estructurals, tot i que no es van observar diferències en la percepció sensorial. El procés de panificació va oferir la possibilitat de modificar l'estructura del pa. De fet, la variació de la forma de la massa va donar lloc a pans amb diferents propietats d'estructura i textura de la molla. La digestió dels pans amb diferent estructura de molla va confirmar que es disgregaven de manera diferent, produint variacions en la posterior digestibilitat del midó. Una vegada que es va establir la importància de la microestructura de la molla en la digestió del midó, es va canviar l'enfocament per a enllaçar la microestructura dels gels de midó amb la seua digestió in vitro. Els gels obtinguts amb midó de diferent fonts botàniques van mostrar diferent digestibilitat, el que es va relacionar amb la seua microestructura, però també amb el seu contingut d'amilosa. Considerant l'acció dels enzims digestius (α-amilasa i α-glucosidasa) sobre la hidròlisi del midó, es van estudiar diferents compostos fenòlics per a comprendre les interaccions entre els fenòlics i els enzims o substrats. La forma més eficaç d'inhibir els enzims era incubar-los amb àcids fenòlics. Es va necessitar una major concentració de l'inhibidor quan els compostos fenòlics interactuaven prèviament amb el substrat, a causa de la seua retenció dins del gel de midó. L'estructura química dels àcids fenòlics controlava la inhibició de l'enzim. Així mateix, els extractes fenòlics complexos, com els extrets de l'alga A. nodosum, podrien utilitzar-se per a inhibir els enzims digestius, mostrant major efecte inhibidor quan van ser prèviament incubats amb l'enzim, a causa de l'existència de complexos carbohidrat-polifenols amb les seues diferents capacitats inhibitòries. A més, els àcids fenòlics van afectar les propietats de pegat i, per tant, la estructura i textura dels gels de midó. No obstant, estos canvis en la estructura i textura dels gels no van ser suficients per a controlar la hidròlisi enzimàtica del midó, que estava relacionada amb l'estructura química dels àcids fenòlics i les seues propietats. En general, la microestructura de la molla de pa o gel de midó pot limitar l'accessibilitat dels enzims digestius, la qual cosa reduiria la hidròlisi del midó. A més, la inclusió d'àcids fenòlics en aliments a base de midó podria ser l'alternativa per a reduir el grau de digestió del midó en inhibir aquests enzims. / [EN] Due to the increasing importance of diet on health management, it remains of utmost interest to unravel how food is processed in the human digestive system. Food structure can significantly influence food processing, affecting its performance during eating and digestion. Specifically, the digestion of carbohydrates-based foods requires further insight due to their contribution to blood glucose levels. The knowledge of starch digestion kinetics will contribute to design tailored foods for managing postprandial glucose levels. The objective of this doctoral thesis was to acquire a better understanding of the impact of microstructure on starch digestion and how digestive enzymes might be modulated by the use of phenolic compounds. With that purpose, the role of bread structure on in vivo mastication, and in vitro digestion was evaluated. Subsequently, starch gels from different sources were produced and digested in an in vitro oro-gastro-intestinal digestion system to analyze the impact of gel microstructure. After the microstructure studies on bread and starch gels, different phenolic acids or seaweed polyphenolic extracts were explored as inhibitors of starch digestive enzymes, and the involvement of starch gel microstructure on the enzymatic digestion was assessed. Mastication of toasted wheat breads was affected by their different structures, despite no differences in the sensory perception was observed. Bolus texture was also altered by bread structure and texture. The breadmaking process offered the possibility to modify the bread structure. In fact, varying dough shaping led to breads with different crumb structure and texture properties. After stressing the importance of selecting the in vitro oral processing method used to simulate mastication, the further digestion of the bread with different crumb structure confirmed that they were differently disaggregated yielding variations on posterior starch digestibility. Once stating the importance of crumb microstructure on starch digestion, the focus was shifted to connect starch gels microstructure with its in vitro digestion. Gels obtained with a different type of starch, from cereals, pulses, or tubers, showed different digestibility, which was related to their microstructure but also their amylose content. Considering the action of digestive enzymes (α-amylase and α-glucosidase) on starch hydrolysis, different phenolic compounds were studied to understand the interactions between phenolics and either enzymes or substrates. The most effective way to inhibit enzymes was to incubate them with phenolic acids. A higher concentration of the inhibitor was needed when phenolic compounds interacted previously with the substrate, due to their retention within the starch gel. The chemical structure of phenolic acids controlled the enzyme inhibition. Similarly, complex phenolic extracts, like those extracted from A. nodosum seaweed could be used to inhibit digestive enzymes, showing greater inhibition effect when they were previously incubated with the enzyme, owing to the existence of carbohydrate-polyphenol complexes their different inhibitory capabilities. In addition, phenolic acids affected pasting properties and therefore gel microstructure and gel texture of starches. However, those changes on gels microstructure and texture were not enough to control starch enzymatic hydrolysis, which was related to the specific chemical structure of the phenolic acids and their properties. Overall, crumb or gel microstructure can limit digestive enzymes accessibility, which would reduce the starch hydrolysis. Moreover, the inclusion of phenolic acids on starch-based foods might be the alternative to reduce the extent of starch digestion by inhibiting digestive enzymes. / Authors acknowledge the financial support of the Spanish Ministry of Science, Innovation and Universities (Project RTI2018-095919-B-C21) funded by MCIN/AEI/10.13039/501100011033, “ERDF A way of making Europe” by the “European Union”, Generalitat Valenciana (Project Prometeo 2017/189) and Xunta de Galicia (ED431B 2019/01). This work is based upon the work from COST Action 18101 SOURDOMICS – Sourdough biotechnology network towards novel, healthier and sustainable food and bioprocesses, where A. Aleixandre was supported by COST (European Cooperation in Science and Technology). COST is a funding agency for research and innovation networks. / Aleixandre Agustín, A. (2022). Going from Digestion to Microstructure of Starch-Based Food Products: Understanding the Role of Polyphenols [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/181137 / Compendio