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Colonic Metabolism of Phenolic Compounds: from in Vitro to in Vivo Approaches Juana Mosele

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Colonic Metabolism of Phenolic Compounds: from in Vitro to in Vivo Approaches Juana Mosele Nom/Logotip de la Universitat on s’ha llegit la tesi Colonic metabolism of phenolic compounds: from in vitro to in vivo approaches Juana Mosele http://hdl.handle.net/10803/378039 ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs. ADVERTENCIA. El acceso a los contenidos de esta tesis doctoral y su utilización debe respetar los derechos de la persona autora. Puede ser utilizada para consulta o estudio personal, así como en actividades o materiales de investigación y docencia en los términos establecidos en el art. 32 del Texto Refundido de la Ley de Propiedad Intelectual (RDL 1/1996). Para otros usos se requiere la autorización previa y expresa de la persona autora. En cualquier caso, en la utilización de sus contenidos se deberá indicar de forma clara el nombre y apellidos de la persona autora y el título de la tesis doctoral. No se autoriza su reproducción u otras formas de explotación efectuadas con fines lucrativos ni su comunicación pública desde un sitio ajeno al servicio TDR. Tampoco se autoriza la presentación de su contenido en una ventana o marco ajeno a TDR (framing). Esta reserva de derechos afecta tanto al contenido de la tesis como a sus resúmenes e índices. WARNING. Access to the contents of this doctoral thesis and its use must respect the rights of the author. It can be used for reference or private study, as well as research and learning activities or materials in the terms established by the 32nd article of the Spanish Consolidated Copyright Act (RDL 1/1996). Express and previous authorization of the author is required for any other uses. In any case, when using its content, full name of the author and title of the thesis must be clearly indicated. Reproduction or other forms of for profit use or public communication from outside TDX service is not allowed. Presentation of its content in a window or frame external to TDX (framing) is not authorized either. These rights affect both the content of the thesis and its abstracts and indexes. JUANA I. MOSELE COLONIC METABOLISM OF PHENOLIC COMPOUNDS: FROM IN VITRO TO IN VIVO APPROACHES Doctoral Thesis Directed by María José Motilva Casado, PhD Co-directed by Alba Macià Puig, PhD Antioxidants Research Group Department of Food Technology University of Lleida Lleida, 2016 Dissertation presented by Juana Inés Mosele to obtain the PhD degree from the University of Lleida. This Doctoral Thesis has been supervised by María José Motilva Casado and Alba Macià Puig. The present work has been carried out in the Antioxidant Research Goup in the Department of Food Technology and is included in “Ciencia i Tecnologia Agraria i Alimentaria” doctoral program. The present Doctoral Thesis is framed on the context of two different projects: The MEFOP project: Metabolic Fate of Olive Oil Phenolic Compounds in Humans: Study of metabolic pathways and tissue distribution. The INCOMES project: Guide for the substantiation of health claims in foods: immune, cognitive functions and metabolic syndrome (Collaborative project between Food Companies & Research Centers). The financing of the PhD candidate was through a doctoral grant from the Generalitat de Catalunya (Febrary 2013 – January 2016). This Doctoral Thesis has received a grant for linguistic revision from the Language Institute at the University of Lleida (2016 call). PhD Candidate Juana Inés Mosele Director María José Motilva Casado, PhD Signature of approval Co-director Alba Macià Puig, PhD Signature of approval De todos los instrumentos del hombre, el más asombroso es, sin duda, el libro. Los demás son extensiones de su cuerpo. El microscopio, el telescopio, son extensiones de su vista; el teléfono es extensión de la voz; luego tenemos el arado y la espada, extensiones del brazo. Pero el libro es otra cosa: el libro es una extensión de la memoria y la imaginación. Jorge Luis Borges AKNOWLEDGMENTS Tras tres años de trabajo y dedicación y a pesar de algunos altibajos, perduran los buenos momentos. Debo agradecer de manera especial y sincera a mi directora de tesis María José Motilva, por aceptarme como miembro de su equipo y por brindarme su incondicional apoyo y confianza a lo largo de estos años. Lograste transmitirme tu pasión por la investigación y la importancia de no bajar los brazos y seguir intentándolo. A mi co- directora y compañera de grupo Alba, tu paciencia y ganas de ayudar han sido claves para mi, gracias por estar en cada momento. A mis chicas juernes por la compañía y momentos imborrables. Para mis compañeros del Departamento de Tecnología de los Alimentos, gracias por esos buenos momentos tanto dentro como fuera del ámbito laboral. Ocupan y ocuparán un lugar importante en mis recuerdos, siempre. I would especially like to thanks to Professor Jeremy Spencer and all the members of the Human Nutrition Research Group of the University of Reading for their warm welcome during my 4 month of stay with them. A Ana y Fran, mi familia de corazón. En especial a mis padres por su incondicional apoyo, capaz de atravesar oceános. The present Doctoral Thesis is based on the following publications: Publication I: Mosele, J.I., Martín-Peláez, S., Macià, A., Farràs, M., Valls, R.M., Catalán, U., Motilva, M.J. Faecal microbial metabolism of olive oil phenolic compounds: In vitro and in vivo approaches. Molecular Nutrition and Food Research, 2014, 58, 1809-1819. Publication II: Mosele, J.I., Martín-Peláez, S., Macià, A., Farràs, M., Valls, R.M., Catalán, U., Motilva, M.J. Study of the catabolism of thyme phenols combining in vitro fermentation and human intervention. Journal of Agricultural and Food Chemistry, 2014, 62, 10954- 10961. Publication III: Martín-Peláez, S., Mosele, J.I., Pizarro, N., Farràs, M., de la Torre, R., Subirana, I., Pérez-Cano, F.J., Castañer, O., Solà, R., Fernández-Castillejo, S., Heredia, S., Farré, M., Motilva, M.J., Fitó, M. Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: implications of human gut microbiota. European Journal of Nutrition, 2015; 13. Article in Press. DOI: 10.1007/s00394-015-1063-2. Publication IV: Mosele, J.I., Macià, A., Romero, M.P., Motilva, M.J., Rubió, L. Application of in vitro gastrointestinal digestion and colonic fermentation models to pomegranate products (juice, pulp and peel extract) to study the stability and catabolism of phenolic compounds. Journal of Functional Foods, 2015 14, 529-540. Publication V: Mosele, J.I., Gosalbes, M.J., Macià, A., Rubió, L., Vázquez-Castellanos, J.F., Jiménez Hernández, N., Moya, A., Latorre, A., Motilva, M.J. Effect of daily intake of pomegranate juice on fecal microbiota and feces metabolites from healthy volunteers. Molecular Nutrition and Food Research, 2015, 59, 1942-1953. Publication VI: Mosele, J.I., Macià, A., Romero, M.P., Motilva, M.J. Stability and metabolism of Arbutus unedo bioactive compounds (phenolics and antioxidants) under in vitro digestion and colonic fermentation. Food Chemistry, 2016, 201, 120-130. Publication VII: Mosele, J.I., Macià, A., Motilva, M.J. Understanding of human metabolic pathways of different sub-classes of phenols from Arbutus unedo fruit after an acute intake. Food and Function. 2016., DOI: 10.1039/C6FO00181E. Publication VIII: Mosele, J.I., Macià, A., Motilva, M.J. Metabolic and microbial modulation of the large intestine ecosystem by non-absorbed diet phenolic compounds: A review. Molecules, 2015, 20, 17429-17468. ABSTRACT Phenolic compounds are a group phytochemicals widely but not uniformly distributed in the plant kingdom. These compounds have generated great expectations in the scientific community as natural therapeutics due to their antioxidant, anti-inflammatory and anticarcinogenic properties. In an attempt to associate the intake of phenolic compounds with reduced risk of chronic diseases, much effort has been invested in the phenolic characterization of plant-based products. Phenolic compounds are usually taken orally through food or supplements intake. The gastrointestinal tract, therefore, is the main route of entrance to the body. Initial attention has been focused on studying the bioavailability of the native compounds present in food. Nevertheless, their apparent low bioavailability has awoken the possibility of contemplating other related metabolites rather than the original forms. The obstinacy to really cover the general metabolism of phenolic compounds in the human body provided their colonic fate with a central role. This is partly explained because phenolic compounds are modestly absorbed and, therefore, a considerable amount of unmetabolized products reaches the colon. The different works that make up the body of this Doctoral Thesis are focused on the study of the colonic metabolism of the more representative phenolic compounds present in three plant-based products. The products concerned were enriched olive oil in its own phenolic compounds and in combination with thyme phenolic compounds, pomegranate and Arbutus unedo (strawerry tree) fruit. In-vitro fermentation and human interventions were conducted for the purpose of exploring the fate of phenolic compounds in the gut.
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