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International audience; The Mediterranean-type diet combines several foods and nutrients already individually proposed as potential protective factors against adverse health outcomes, such as cardiovascular diseases. The aim of the present study was to describe the association between adherence to a Mediterranean diet (MeDi) and intake of energy, macronutrients, and micronutrients. The study sample consisted of 1,595 individuals from Bordeaux, France, included in 2001-2002 in the Three-City Study. Adherence to a MeDi (scored as 0 to 9) was computed from a food frequency questionnaire (FFQ). Total energy intake (EI) and nutrient intake were evaluated on a 24 h recall. Statistical analyses were stratified by gender. Both in men and women, greater MeDi adherence was associated with higher total vegetal protein, polyunsaturated fatty acids (PUFA), notably n - 6 PUFA, and lower total saturated fat intakes, as expressed in percentage of EI. Higher total monounsaturated fat and oleic acid intakes (% EI) were observed with greater MeDi adherence in men. Women with the highest MeDi adherence exhibited a higher mean carbohydrate, polysaccharide, and total n - 3 PUFA intakes (% EI). The consumption of fibers; vitamins B6, C, and E; folate; magnesium; potassium; and iron increased with greater MeDi adherence, both in men and women. However, consumption of calcium significantly decreased with greater MeDi adherence in women, while the ratio of n - 6/n - 3 PUFA precursors increased. This cross-sectional study provides the nutrient-related basis of the Mediterranean-type diet of French elderly community dwellers, which might participate to its well-documented beneficial effects on health.

The sporadic form of Alzheimer's disease is one of the most widespread neurodegenerative diseases worldwide, yet remains incurable today; pharmacological treatments only alleviate the symptoms without slowing down the disease progression. In a "life-course" model of interaction between genetic predisposition and environmental factors, endotoxins - toxic substances of bacterial origin with strong pro-inflammatory potential - emerge as detrimental factors in the concept of healthy aging. Diet, theoretically capable of acting both on the composition of the gut microbiota (the body’s main endotoxin reservoir) and of influencing the passage of endotoxins into the bloodstream, represents a promising strategy in modulating endotoxin exposure. The objectives of this thesis were (i) to assess the association between dietary patterns and a biomarker of total plasma endotoxin exposure, and (ii) to assess the association between biomarkers of plasma endotoxin exposure and the risk of Alzheimer's disease, in an elderly population. Given the multidimensional nature of diet, two complementary approaches were used to assess dietary exposure. The adherence to the Mediterranean diet (based on a a priori confirmatory approach) as well as adherence to a “prudent” type diet (derived from a a posteriori exploratory approach) mainly characterized by a high consumption of fruits and vegetables and a low one in cookies, were inversely associated with circulating levels of 3-hydroxy fatty acids, a proxy of the total plasma endotoxins exposure. Conversely, a "south-west" diet mainly characterized by a high consumption of alcohol, meat, processed meat and to a lesser extent legumes and cereals was associated with higher levels of 3-hydroxy fatty acids. These results suggested that the diet could be a promising strategy to target endotoxemia and its consequence on inflammatory processes. While no association has been observed between the baseline levels of 3-hydroxy fatty acids and the risk of Alzheimer's disease, higher plasma levels of Lipopolysaccharides-Binding Protein (LBP) - an endotoxin transport protein - were associated with an increased risk of Alzheimer's disease more than a decade later. Given that LBP is considered as a biomarker of the current biological activity of endotoxins compared with the total amount of circulating endotoxins, and essential in the initiation of the immune and inflammatory response to endotoxins, these results suggested the involvement of endotoxemia in the pathogenesis of Alzheimer's disease., La forme sporadique de la maladie d’Alzheimer représente l’une des maladies neurodégénératives les plus répandues à travers le monde, demeurant toutefois incurable de nos jours ; les traitements pharmacologiques ne permettant que d’en atténuer les symptômes sans pour autant freiner la progression de la maladie. Dans un modèle « vie-entière » d’interaction entre prédisposition génétique et facteurs environnementaux, les endotoxines - des substances toxiques d’origine bactérienne à fort potentiel pro-inflammatoire - émergent en tant que facteurs préjudiciables dans le concept de vieillissement en bonne santé. L’alimentation, théoriquement capable d’agir à la fois sur la composition du microbiote intestinal (principal réservoir à endotoxines de l’organisme) et d’influencer le passage des endotoxines vers la circulation sanguine, représente une stratégie prometteuse dans la modulation de l’exposition aux endotoxines. Les objectifs de cette thèse ont été d’une part (i) d’évaluer l’association entre des profils alimentaires et un biomarqueur de l’exposition plasmatique aux endotoxines, et d’autre part (ii) d’évaluer l’association entre des biomarqueurs de l’exposition plasmatique aux endotoxines et le risque de maladie d’Alzheimer, au sein d’une population âgée. Compte-tenu de la nature multidimensionnelle de l’alimentation, deux approches complémentaires ont été utilisées pour définir l’exposition nutritionnelle. Le score d’adhérence au régime Méditerranéen (construit selon une approche confirmatoire a priori) ainsi que l’adhérence à un régime de type « prudent » (dérivé d’une approche exploratoire a posteriori) caractérisé principalement par une consommation riche en fruits et légumes et pauvre en biscuits, étaient inversement associés aux taux circulants d’acides gras 3-hydroxylés, un proxy de la quantification totale en endotoxines plasmatiques. À l’inverse, un régime de type « sud-ouest » caractérisé principalement par une consommation riche en alcool, viande, charcuterie et dans une moindre mesure en légumineuses et céréales était associé à des taux plus élevés d’acides gras 3-hydroxylés. Ces résultats suggéraient que l’alimentation pourrait être une piste prometteuse ciblant l’endotoxémie, et donc les processus inflammatoires en découlant, chez la personne âgée. Alors qu’aucune association n’a été mise en évidence entre les taux d’acides gras 3-hydroxylés à l’inclusion et le risque de survenue d’une maladie d’Alzheimer, des taux plasmatiques plus élevés de Lipopolysaccharides-Binding Protein (LBP) - protéine de transport des endotoxines - étaient associés à un sur-risque de maladie d’Alzheimer plus d’une décennie après. Étant donné que la LBP, essentielle dans l’initiation de la réponse immunitaire et inflammatoire aux endotoxines, est considérée comme un biomarqueur de l’activité biologique effective des endotoxines comparativement à la quantité totale en endotoxines circulantes, ces résultats suggéraient l’implication de l’endotoxémie dans la pathogenèse de la maladie d’Alzheimer.