24 research outputs found

    Variations on a Theme: A Bibliography on Approaches to Theorem Proving Inspired From Satchmo

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    This articles is a structured bibliography on theorem provers, approaches to theorem proving, and theorem proving applications inspired from Satchmo, the model generation theorem prover developed in the mid 80es of the 20th century at ECRC, the European Computer- Industry Research Centre. Note that the bibliography given in this article is not exhaustive

    A framework for integrating and transforming between ontologies and relational databases

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    Bridging the gap between ontologies, expressed in the Web Ontology Language (OWL), and relational databases is a necessity for realising the Semantic Web vision. Relational databases are considered a good solution for storing and processing ontologies with a large amount of data. Moreover, the vast majority of current websites store data in relational databases, and therefore being able to generate ontologies from such databases is important to support the development of the Semantic Web. Most of the work concerning this topic has either (1) extracted an OWL ontology from an existing relational database that represents as exactly as possible the relational schema, using a limited range of OWL modelling constructs, or (2) extracted a relational database from an existing OWL ontology, that represents as much as possible the OWL ontology. By way of contrast, this thesis proposes a general framework for transforming and mapping between ontologies and databases, via an intermediate low-level Hyper-graph Data Model. The transformation between relational and OWL schemas is expressed using directional Both-As-View mappings, allowing a precise definition of the equivalence between the two schemas, hence data can be mapped back and forth between them. In particular, for a given OWL ontology, we interpret the expressive axioms either as triggers, conforming to the Open-World Assumption, that performs a forward-chaining materialisation of inferred data, or as constraints, conforming to the Closed-World Assumption, that performs a consistency checking. With regards to extracting ontologies from relational databases, we transform a relational database into an exact OWL ontology, then enhance it with rich OWL 2 axioms, using a combination of schema and data analysis. We then apply machine learning algorithms to rank the suggested axioms based on past users’ relevance. A proof-of-concept tool, OWLRel, has been implemented, and a number of well-known ontologies and databases have been used to evaluate the approach and the OWLRel tool.Open Acces

    Pseudo-contractions as Gentle Repairs

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    Updating a knowledge base to remove an unwanted consequence is a challenging task. Some of the original sentences must be either deleted or weakened in such a way that the sentence to be removed is no longer entailed by the resulting set. On the other hand, it is desirable that the existing knowledge be preserved as much as possible, minimising the loss of information. Several approaches to this problem can be found in the literature. In particular, when the knowledge is represented by an ontology, two different families of frameworks have been developed in the literature in the past decades with numerous ideas in common but with little interaction between the communities: applications of AGM-like Belief Change and justification-based Ontology Repair. In this paper, we investigate the relationship between pseudo-contraction operations and gentle repairs. Both aim to avoid the complete deletion of sentences when replacing them with weaker versions is enough to prevent the entailment of the unwanted formula. We show the correspondence between concepts on both sides and investigate under which conditions they are equivalent. Furthermore, we propose a unified notation for the two approaches, which might contribute to the integration of the two areas

    Invariant-free deduction systems for temporal logic

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    In this thesis we propose a new approach to deduction methods for temporal logic. Our proposal is based on an inductive definition of eventualities that is different from the usual one. On the basis of this non-customary inductive definition for eventualities, we first provide dual systems of tableaux and sequents for Propositional Linear-time Temporal Logic (PLTL). Then, we adapt the deductive approach introduced by means of these dual tableau and sequent systems to the resolution framework and we present a clausal temporal resolution method for PLTL. Finally, we make use of this new clausal temporal resolution method for establishing logical foundations for declarative temporal logic programming languages. The key element in the deduction systems for temporal logic is to deal with eventualities and hidden invariants that may prevent the fulfillment of eventualities. Different ways of addressing this issue can be found in the works on deduction systems for temporal logic. Traditional tableau systems for temporal logic generate an auxiliary graph in a first pass.Then, in a second pass, unsatisfiable nodes are pruned. In particular, the second pass must check whether the eventualities are fulfilled. The one-pass tableau calculus introduced by S. Schwendimann requires an additional handling of information in order to detect cyclic branches that contain unfulfilled eventualities. Regarding traditional sequent calculi for temporal logic, the issue of eventualities and hidden invariants is tackled by making use of a kind of inference rules (mainly, invariant-based rules or infinitary rules) that complicates their automation. A remarkable consequence of using either a two-pass approach based on auxiliary graphs or aone-pass approach that requires an additional handling of information in the tableau framework, and either invariant-based rules or infinitary rules in the sequent framework, is that temporal logic fails to carry out the classical correspondence between tableaux and sequents. In this thesis, we first provide a one-pass tableau method TTM that instead of a graph obtains a cyclic tree to decide whether a set of PLTL-formulas is satisfiable. In TTM tableaux are classical-like. For unsatisfiable sets of formulas, TTM produces tableaux whose leaves contain a formula and its negation. In the case of satisfiable sets of formulas, TTM builds tableaux where each fully expanded open branch characterizes a collection of models for the set of formulas in the root. The tableau method TTM is complete and yields a decision procedure for PLTL. This tableau method is directly associated to a one-sided sequent calculus called TTC. Since TTM is free from all the structural rules that hinder the mechanization of deduction, e.g. weakening and contraction, then the resulting sequent calculus TTC is also free from this kind of structural rules. In particular, TTC is free of any kind of cut, including invariant-based cut. From the deduction system TTC, we obtain a two-sided sequent calculus GTC that preserves all these good freeness properties and is finitary, sound and complete for PLTL. Therefore, we show that the classical correspondence between tableaux and sequent calculi can be extended to temporal logic. The most fruitful approach in the literature on resolution methods for temporal logic, which was started with the seminal paper of M. Fisher, deals with PLTL and requires to generate invariants for performing resolution on eventualities. In this thesis, we present a new approach to resolution for PLTL. The main novelty of our approach is that we do not generate invariants for performing resolution on eventualities. Our method is based on the dual methods of tableaux and sequents for PLTL mentioned above. Our resolution method involves translation into a clausal normal form that is a direct extension of classical CNF. We first show that any PLTL-formula can be transformed into this clausal normal form. Then, we present our temporal resolution method, called TRS-resolution, that extends classical propositional resolution. Finally, we prove that TRS-resolution is sound and complete. In fact, it finishes for any input formula deciding its satisfiability, hence it gives rise to a new decision procedure for PLTL. In the field of temporal logic programming, the declarative proposals that provide a completeness result do not allow eventualities, whereas the proposals that follow the imperative future approach either restrict the use of eventualities or deal with them by calculating an upper bound based on the small model property for PLTL. In the latter, when the length of a derivation reaches the upper bound, the derivation is given up and backtracking is used to try another possible derivation. In this thesis we present a declarative propositional temporal logic programming language, called TeDiLog, that is a combination of the temporal and disjunctive paradigms in Logic Programming. We establish the logical foundations of our proposal by formally defining operational and logical semantics for TeDiLog and by proving their equivalence. Since TeDiLog is, syntactically, a sublanguage of PLTL, the logical semantics of TeDiLog is supported by PLTL logical consequence. The operational semantics of TeDiLog is based on TRS-resolution. TeDiLog allows both eventualities and always-formulas to occur in clause heads and also in clause bodies. To the best of our knowledge, TeDiLog is the first declarative temporal logic programming language that achieves this high degree of expressiveness. Since the tableau method presented in this thesis is able to detect that the fulfillment of an eventuality is prevented by a hidden invariant without checking for it by means of an extra process, since our finitary sequent calculi do not include invariant-based rules and since our resolution method dispenses with invariant generation, we say that our deduction methods are invariant-free.CYCIT (ref. TIC98-0949-C02-02), CYCIT (ref. TIC2001-2476-C03-03), CYCIT (ref. TIN2004-07925-C03-03), CICYT (ref. TIN2007-66523), University of the Basque Country (ref. UPV-EHU GIU07/35), University of the Basque Country (ref. UFI11/45

    Déterminants génétiques du contrôle de la masse cardiaque et/ou de la taille des cardiomyocytes dans des croisements expérimentaux de rongeurs

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

    Compilation efficace pour FPGA reconfigurable dynamiquement

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    Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

    Reconstruction par tractographie des fibres de la matière blanche chez l'adulte sain ou souffrant de lésions neurologiques

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    Le cerveau est l'un des organes les plus complexes et les plus méconnus du corps humain. Grâce à l'imagerie par résonance magnétique (IRM) et plus précisément l'imagerie de diffusion, il est maintenant possible de reconstruire la connectivité de la matière blanche. Avec le temps ou la maladie, le cerveau peut subir des altérations pouvant modifier la connectivité de la matière blanche. Il est important de prendre en compte ces altérations pour pouvoir effectuer des analyses précises des connexions cérébrales.\\ La majorité des algorithmes utilisés dans le domaine de l'imagerie cérébrale sont développés avec des images provenant de sujets jeunes et sains. Cependant, la réalité de la recherche appliquée et de la clinique est tout autre. Les outils utilisés doivent donc être modulaires, que ce soit pour le traitement d'un sujet sain, âgé ou souffrant d'une pathologie.\\ Premièrement, cette thèse présente une mise en contexte. Ensuite, cette thèse s'intéresse au développement de méthodes pour la tractographie en milieu pratique et d'outils automatisés de traitement de l'IRM de diffusion (IRMd). Le guide sur la tractographie en milieu pratique est un chapitre de livre qui a pour but de former et conseiller les chercheurs cliniciens pour l'obtention d'un tractogramme répondant à leurs besoins. Les outils développés dans cette thèse sont composés d'un algorithme de traitement de l'IRMd automatisé appelé TractoFlow, ainsi que d'un outil de segmentation robuste aux lésions de matière blanche liées au vieillissement appelé DORIS. TractoFlow permet d'obtenir un tractogramme à partir des images d'IRMd brute facilement, rapidement et de manière reproductible. Notre second algorithme, DORIS, permet d'obtenir une segmentation des tissus cérébraux en 10 classes à partir des mesures de l'IRMd tout en améliorant la qualité de la tractographie anatomiquement contrainte. En guise de discussion, cette thèse présente deux projets futurs: DORIS adapté aux lésions et la tractographie adaptative au tissu sous-jacent. DORIS adapté aux lésions à pour but d'ajouter une 11ème classe afin de segmenter les lésions liées à la sclérose en plaque. Ensuite la tractographie adaptive présente une nouvelle manière de reconstruire les fibres de matière blanche en adaptant les paramètre de reconstruction suivant le tissu traversé. Cette thèse vise donc à remplir 2 objectifs: le premier est de pouvoir traiter et analyser la connectivité cérébrale chez des sujets jeunes, des sujets âgés ou souffrant d'une pathologie, le second est de répondre aux besoins du milieu clinique et de la recherche appliquée en étant simple et modulaire. Finalement, cette thèse conclue en présentant l'impact des différents outils sur la communauté et en discutant de ma vision du futur de l'IRMd et de la tractographie.\

    Dissection moléculaire de la fonction activatrice AF-1 du récepteur aux oestrogènes alpha dans la physiopathologie vasculaire et la prolifération utérine

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    Les œstrogènes influencent de nombreuses maladies comme le cancer de l'endomètre et les maladies cardiovasculaires. Leurs actions majeures sont relayées par le récepteur aux œstrogènes ERa, régulant la transcription de gènes cibles via deux fonctions activatrices AF-1 et AF-2. Grâce à l'utilisation de souris invalidées pour AF-1, mon équipe a rapporté que l'AF-1 n'était pas nécessaire pour l'action vasculoprotectrice du 17ß-œstradiol (E2), principal œstrogène naturel. Durant ma thèse, nous avons démontré que : i) le tamoxifène, modulateur sélectif des ERs,protège de l'athérosclérose via AF-1, contrairement à l'effet de l'E2 mais n'accélère pas la ré-endothélialisation, ii) l'AF-1 du ERa est nécessaire pour la régulation de la transcription et de la prolifération cellulaire dans l'utérus en réponse à l'E2 et au tamoxifène. Ainsi, ce travail contribue à la dissection moléculaire de l'action du Era in vivo, qui pourrait poser les bases d'une optimisation de la modulation du ERa.Estrogens influence most of the physiological processes in mammals, in particular reproduction and vascular system. Thus, it is not surprising that these steroid hormones influence numerous diseases, including breast and endometrium cancers, as well as cardiovascular diseases. These actions are mediated by two nuclear receptors, estrogen receptors ERa and ERß, which regulate target gene transcription through two independent activation functions AF-1 and AF-2. Using ERa deficient mice or electively targeting AF-1, my team has previously demonstrated that ERa is required for the E2 vasculoprotective actions of 17ß-estradiol (E2), the main natural estrogen. In contrast, activation of AF-1 of ERa is dispensable for atheroprotection, increase of NO relaxation and endothelial healing. During my phD, we have shown that: 1) tamoxifen, a selective ER modulator, used more than 30 years for breast cancer treatment in premenopausal women, prevents atherosclerosis but not accelerates endothelial healing. This atheroprotective effect is ERa-dependant and in contrast to E2, needs its AF-1, 2) AF-1of ERa is necessary to the regulation of gene transcription and cell proliferation in the uterus in response to E2 or tamoxifen. However a residual uterine hypertrophy after chronic E2 treatment persists in mice lacking AF-1 of ERa, potentially due to a stromal edema resulting to the persistence of Vegf-a induction. Furthermore uterine epithelial apoptosis and response to progesterone are largely altered in these mice. Thus, my PhD contributes to the molecular dissection of ERa activation in vivo, which could pave the way of an optimized ERa modulation. Indeed, the selective activation of ERa inducing beneficial effects of E2 without stimulating deleterious effects represents a major therapeutic interest

    Identification of novel early biomarkers of cardiovascular disease risk and their relationships with bioactive dietary compounds: metabolomic and gut metagenomic approaches

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    Són diversos els factors de risc que contribueixen a la càrrega de malalties cardiovasculars (MCV). La hipertensió i la hipercolesterolèmia es troben entre els principals factors de risc causals i modificables de MCV que han conduït al desenvolupament d'importants models predictius. No obstant, no tots els factors de risc tradicionals són suficients per identificar totes les persones en risc. La identificació de nous biomarcadors de risc de MCV basats en el metaboloma i el microbioma intestinal són prometedors per a la detecció primerenca de MCV. L'objectiu d'aquesta tesi és identificar nous biomarcadors primerencs de risc de MCV basats en la microbiota intestinal i metabòlits adequats en etapes preliminars d'hipertensió, hipercolesterolèmia i altres factors de risc de MCV a través de la integració d'enfocaments multiòmics, així com avaluar les relacions amb compostos dietètics bioactius per especular sobre possibles vies. A través d'un enfoc observacional, en un primer estudi transversal on van participar subjectes amb hipertensió grau 1 no tractada i sans, mitjançant l'aplicació de metabolòmica i metagenòmica intestinal, es van identificar nous biomarcadors microbians i metabòlits. Entre ells, Bacteroides spp. i els àcids grassos de cadena curta fecals es van associar fortament amb la hipertensió. A més, els compostos fenòlics de la dieta van mostrar relacions positives i negatives amb els biomarcadors enriquits en hipertensos, el que va suggerir una nova via per la qual podrien estar involucrats en la patogènesi/prevenció de la hipertensió. En un segon estudi transversal en subjectes sans i amb hipercolesterolèmia moderada a alta, mitjançant l'aplicació de lipidòmica, determinats lisofosfolípids sèrics van ser identificats com a biomarcadors de susceptibilitat/risc idonis en hipercolesterolèmia. Aquests resultats es van verificar en un estudi in vivo en hàmsters. A més, es va trobar una relació positiva entre els lisofosfolípids biomarcadors i els àcids grassos poliinsaturats omega(n) de la dieta, i aquests resultats es van investigar més a fons en una darrera revisió sistemàtica i metanàlisi d'assajos clínics aleatoritzats. Amb els principals biomarcadors identificats en aquesta tesi es proposa un classificador de salut i malaltia fiable per distingir entre l'estat sa i factors de risc de MCV.Son varios los factores de riesgo que contribuyen a la carga de enfermedades cardiovasculares (ECV). La hipertensión y la hipercolesterolemia se encuentran entre los principales factores causales y modificables de ECV que han conducido al desarrollo de importantes modelos predictivos. Sin embargo, no todos los factores de riesgo tradicionales son suficientes para identificar a todas las personas en riesgo. La identificación de nuevos biomarcadores de riesgo de ECV basados en el metaboloma y el microbioma intestinal son prometedores para la detección temprana de ECV. El objetivo de ésta tesis es identificar nuevos biomarcadores tempranos de riesgo de ECV basados en la microbiota intestinal y metabolitos adecuados en etapas preliminares de hipertensión, hipercolesterolemia y otros factores de riesgo de ECV a través de la integración de enfoques multiómicos, así cómo evaluar las relaciones con compuestos dietéticos bioactivos para especular posibles vías. En un primer estudio transversal en el que participaron sujetos con hipertensión grado 1 no tratada y sanos, mediante la aplicación de metabolómica y metagenómica intestinal, se identificaron nuevos biomarcadores microbianos y metabolitos. Entre ellos, Bacteroides spp. y los ácidos grasos de cadena corta fecales se asociaron con la hipertensión. Además, los compuestos fenólicos de la dieta mostraron relaciones positivas y negativas con los biomarcadores enriquecidos en hipertensos, lo que sugirió una nueva vía por la que podrían estar involucrados en la patogénesis/prevención de la hipertensión. En un segundo estudio transversal en sujetos sanos y con hipercolesterolemia moderada a alta, mediante la aplicación de lipidómica, determinados lisofosfolípidos séricos fueron identificados como biomarcadores de susceptibilidad/riesgo idóneos en hipercolesterolemia. Estos resultados se verificaron en un estudio in vivo en hámsters. Además, los lisofosfolípidos biomarcadores y los ácidos grasos poliinsaturados omega(n) de la dieta se relacionaron positivamente, y finalmente, se investigó más a fondo en una revisión sistemática y metanálisis de ensayos clínicos aleatorizados. Con los principales biomarcadores identificados en esta tesis se propone un clasificador de salud/enfermedad fiable para fiable para distinguir el estado sano y factores de riesgo de ECV.Several risk factors contribute to cardiovascular diseases (CVDs) burden worldwide. Causal and modifiable CVD risk factors, such as hypertension and hypercholesterolemia, have led to the development of risk prediction models and to major developments in therapy. However, not all traditional risk factors are enough to identify all at-risk individuals. The identification of novel CVD risk biomarkers based on metabolome and gut microbiome represent exciting gaps in the early detection of CVDs. The aim of this thesis is to identify novel early gut microbiota- and metabolite-based CVD risk biomarkers suitable for the preliminary stages of human hypertension, hypercholesterolemia and other major CVD risk factors through the integration of multiomics approaches, and to assess their relationships with bioactive dietary compounds to speculate about the involved pathways. An observational approach was used. In a cross-sectional study involving nontreated grade 1 hypertensive and normotensive subjects, by application of metabolomics and gut metagenomics, novel gut microbiota- and metabolite-based biomarkers, including a set of bacterial taxa from Bacteroides spp. and faecal short-chain fatty acids, were strongly associated with hypertension. Moreover, dietary phenolic compounds shown positive and negative relationships with hypertensive-enriched biomarkers, suggesting a complex pathway by which they could be involved in the pathogenesis/prevention of hypertension. In a second cross-sectional study in healthy and moderate-to-high hypercholesterolemic subjects, by application of lipidomics, specific serum lysophospholipids were identified as suitable susceptibility/risk biomarkers against the onset of hypercholesterolemia. These findings were verified in an in vivo study in hamsters. In addition, a positive relationship was found between lysophospholipid biomarkers and dietary omega-(n) polyunsaturated fatty acids, and these results were further investigated in a last systematic review and meta-analysis of randomized clinical trials. With the main biomarkers identified in this thesis a reliable health and disease classifier to discern main CVD risk factors from the healthy status is proposed

    Identification of novel early biomarkers of cardiovascular disease risk and their relationships with bioactive dietary compounds: metabolomic and gut metagenomic approaches

    Get PDF
    Són diversos els factors de risc que contribueixen a la càrrega de malalties cardiovasculars (MCV). La hipertensió i la hipercolesterolèmia es troben entre els principals factors de risc causals i modificables de MCV que han conduït al desenvolupament d'importants models predictius. No obstant, no tots els factors de risc tradicionals són suficients per identificar totes les persones en risc. La identificació de nous biomarcadors de risc de MCV basats en el metaboloma i el microbioma intestinal són prometedors per a la detecció primerenca de MCV. L'objectiu d'aquesta tesi és identificar nous biomarcadors primerencs de risc de MCV basats en la microbiota intestinal i metabòlits adequats en etapes preliminars d'hipertensió, hipercolesterolèmia i altres factors de risc de MCV a través de la integració d'enfocaments multiòmics, així com avaluar les relacions amb compostos dietètics bioactius per especular sobre possibles vies. A través d'un enfoc observacional, en un primer estudi transversal on van participar subjectes amb hipertensió grau 1 no tractada i sans, mitjançant l'aplicació de metabolòmica i metagenòmica intestinal, es van identificar nous biomarcadors microbians i metabòlits. Entre ells, Bacteroides spp. i els àcids grassos de cadena curta fecals es van associar fortament amb la hipertensió. A més, els compostos fenòlics de la dieta van mostrar relacions positives i negatives amb els biomarcadors enriquits en hipertensos, el que va suggerir una nova via per la qual podrien estar involucrats en la patogènesi/prevenció de la hipertensió. En un segon estudi transversal en subjectes sans i amb hipercolesterolèmia moderada a alta, mitjançant l'aplicació de lipidòmica, determinats lisofosfolípids sèrics van ser identificats com a biomarcadors de susceptibilitat/risc idonis en hipercolesterolèmia. Aquests resultats es van verificar en un estudi in vivo en hàmsters. A més, es va trobar una relació positiva entre els lisofosfolípids biomarcadors i els àcids grassos poliinsaturats omega(n) de la dieta, i aquests resultats es van investigar més a fons en una darrera revisió sistemàtica i metanàlisi d'assajos clínics aleatoritzats. Amb els principals biomarcadors identificats en aquesta tesi es proposa un classificador de salut i malaltia fiable per distingir entre l'estat sa i factors de risc de MCV.Son varios los factores de riesgo que contribuyen a la carga de enfermedades cardiovasculares (ECV). La hipertensión y la hipercolesterolemia se encuentran entre los principales factores causales y modificables de ECV que han conducido al desarrollo de importantes modelos predictivos. Sin embargo, no todos los factores de riesgo tradicionales son suficientes para identificar a todas las personas en riesgo. La identificación de nuevos biomarcadores de riesgo de ECV basados en el metaboloma y el microbioma intestinal son prometedores para la detección temprana de ECV. El objetivo de ésta tesis es identificar nuevos biomarcadores tempranos de riesgo de ECV basados en la microbiota intestinal y metabolitos adecuados en etapas preliminares de hipertensión, hipercolesterolemia y otros factores de riesgo de ECV a través de la integración de enfoques multiómicos, así cómo evaluar las relaciones con compuestos dietéticos bioactivos para especular posibles vías. En un primer estudio transversal en el que participaron sujetos con hipertensión grado 1 no tratada y sanos, mediante la aplicación de metabolómica y metagenómica intestinal, se identificaron nuevos biomarcadores microbianos y metabolitos. Entre ellos, Bacteroides spp. y los ácidos grasos de cadena corta fecales se asociaron con la hipertensión. Además, los compuestos fenólicos de la dieta mostraron relaciones positivas y negativas con los biomarcadores enriquecidos en hipertensos, lo que sugirió una nueva vía por la que podrían estar involucrados en la patogénesis/prevención de la hipertensión. En un segundo estudio transversal en sujetos sanos y con hipercolesterolemia moderada a alta, mediante la aplicación de lipidómica, determinados lisofosfolípidos séricos fueron identificados como biomarcadores de susceptibilidad/riesgo idóneos en hipercolesterolemia. Estos resultados se verificaron en un estudio in vivo en hámsters. Además, los lisofosfolípidos biomarcadores y los ácidos grasos poliinsaturados omega(n) de la dieta se relacionaron positivamente, y finalmente, se investigó más a fondo en una revisión sistemática y metanálisis de ensayos clínicos aleatorizados. Con los principales biomarcadores identificados en esta tesis se propone un clasificador de salud/enfermedad fiable para fiable para distinguir el estado sano y factores de riesgo de ECV.Several risk factors contribute to cardiovascular diseases (CVDs) burden worldwide. Causal and modifiable CVD risk factors, such as hypertension and hypercholesterolemia, have led to the development of risk prediction models and to major developments in therapy. However, not all traditional risk factors are enough to identify all at-risk individuals. The identification of novel CVD risk biomarkers based on metabolome and gut microbiome represent exciting gaps in the early detection of CVDs. The aim of this thesis is to identify novel early gut microbiota- and metabolite-based CVD risk biomarkers suitable for the preliminary stages of human hypertension, hypercholesterolemia and other major CVD risk factors through the integration of multiomics approaches, and to assess their relationships with bioactive dietary compounds to speculate about the involved pathways. An observational approach was used. In a cross-sectional study involving nontreated grade 1 hypertensive and normotensive subjects, by application of metabolomics and gut metagenomics, novel gut microbiota- and metabolite-based biomarkers, including a set of bacterial taxa from Bacteroides spp. and faecal short-chain fatty acids, were strongly associated with hypertension. Moreover, dietary phenolic compounds shown positive and negative relationships with hypertensive-enriched biomarkers, suggesting a complex pathway by which they could be involved in the pathogenesis/prevention of hypertension. In a second cross-sectional study in healthy and moderate-to-high hypercholesterolemic subjects, by application of lipidomics, specific serum lysophospholipids were identified as suitable susceptibility/risk biomarkers against the onset of hypercholesterolemia. These findings were verified in an in vivo study in hamsters. In addition, a positive relationship was found between lysophospholipid biomarkers and dietary omega-(n) polyunsaturated fatty acids, and these results were further investigated in a last systematic review and meta-analysis of randomized clinical trials. With the main biomarkers identified in this thesis a reliable health and disease classifier to discern main CVD risk factors from the healthy status is proposed
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