Objective markers of usual diet are of interest as alternative or validating tools in nutritional epidemiology research. The main purpose of the work was to assess whether saliva protein composition can reflect dietary habits in older adults, and how type 2 diabetes impacted on the saliva-diet correlates. 214 participants were selected from 2 European cohorts of community-dwelling older adults (3C-Bordeaux and Seniors-ENRICA-2), using a case–control design nested in each cohort. Cases were individuals with type 2 diabetes. Dietary information was obtained using the Mediterranean Diet Adherence Screener (MEDAS). Saliva was successfully obtained from 211 subjects, and its proteome analyzed by liquid chromatography–tandem mass spectrometry. The relative abundance of 246 saliva proteins was obtained across all participants. The salivary proteome differed depending on the intake level of some food groups (especially vegetables, fruits, sweet snacks and red meat), in a diabetic status- and cohort-specific manner. Gene Set Enrichment Analysis suggested that some biological processes were consistently affected by diet across cohorts, for example enhanced platelet degranulation in high consumers of sweet snacks. Minimal models were then fitted to predict dietary variables by sociodemographic, clinical and salivary proteome variables. For the food group «sweet snacks», selected salivary proteins contributed to the predictive model and improved its performance in the Seniors-ENRICA-2 cohort and when both cohorts were combined. Saliva proteome composition of elderly individuals can reflect some aspects of dietary patterns.

BACKGROUND LPS-type endotoxins, naturally found in the gut microbiota, are recognized as triggers of inflammation and emerge as detrimental factors of healthy aging. Nutrition represents a promising strategy to reduce LPS burden, yet little is known about the relation of diet to circulating LPS concentrations. OBJECTIVE The aim was to evaluate the associations between food groups, dietary patterns, and circulating 3-hydroxy fatty acids (3-OH FAs), a proxy of LPS burden. METHODS In a cross-sectional study of 698 French older community-dwelling individuals, 3-OH FA concentrations were measured by LC-tandem MS. Dietary patterns were determined using food-frequency questionnaires. Adherence to a Mediterranean-type diet was computed according to the consumption of 8 food groups (fruits, vegetables, legumes, cereals, fish, olive oil, meat, and dairy products) and alcohol intake (range: 0, low adherence, to 18, high adherence). Three a posteriori dietary patterns were derived from factor analysis: complex carbohydrate (rich in rice, pasta, eggs, poultry, and potatoes), traditional (rich in alcohol, meat, processed meats-cold cuts, and legumes), and prudent (rich in vegetables and fruits and low in cookies) diets. Linear regression models were applied. RESULTS The frequency of consumption of each food group was not associated with 3-OH FA concentrations. Greater adherence to both the Mediterranean diet and the prudent diet were associated with lower circulating 3-OH FAs (β [95% CI] for each additional point of score: -0.12 [-0.22, -0.01] and -0.27 [-0.48, -0.07], respectively). In contrast, greater adherence to the traditional diet was associated with higher concentration of 3-OH FAs (β [95% CI] 0.22 [0.001, 0.46]). The adherence to the complex-carbohydrate diet was not associated with 3-OH FA concentrations. CONCLUSIONS Based on 2 complementary approaches, the identified plant-based dietary patterns were associated with lower 3-OH FA concentrations, and thus a lower LPS burden, which is considered a potent trigger of inflammatory response.

Le syndrome métabolique (SMet), dont l’obésité abdominale représente l’une des composantes les plus fréquemment observées, atteint des niveaux épidémiques dans le monde. L’inflammation chronique de bas grade est considérée comme un mécanisme contribuant au développement de l’obésité et du SMet, cependant les facteurs qui initient et maintiennent cette inflammation restent peu élucidés, notamment chez la personne âgée. L’endotoxémie métabolique, définie comme l’augmentation transitoire des taux circulants de lipopolysaccharides (LPS) suite à un régime alimentaire notamment riche en lipides, a été proposée comme cause majeure de l’inflammation, et cette voie pourrait contribuer à l’obésité et au SMet. L’objectif de cette étude était d’analyser les relations entre les taux de LPS-binding protein (LBP), une protéine impliquée dans la réponse inflammatoire induite par les LPS, et le SMet chez les personnes âgées. Les participants issus du suivi à 10 ans de la cohorte des 3 cités–Bordeaux et disposant d’informations sociodémographiques, anthropométriques, cliniques et d’un échantillon sanguin, ont été inclus dans cette étude. Les taux circulants de LBP ont été mesurés par dosage ELISA et le SMet a été défini selon les critères du NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) comme la présence d’au moins 3 anomalies métaboliques parmi une obésité abdominale (tour de taille > 88 cm pour les femmes et > 102 cm pour les hommes), un taux élevé de triglycérides (> 150 mg/dL), un taux faible de HDL (< 40 mg/dL pour les hommes et <50 mg/dL pour les femmes), une hyperglycémie (> 110 mg/dL ou prise d’un traitement anti-diabétique) et une tension artérielle élevée (pression artérielle systolique > 130 mmHg ou pression diastolique > 85 mmHg ou prise d’un traitement anti-hypertenseur). Parmi les 303 participants inclus dans l’étude et âgés en moyenne de 82 ans, 19,8 % d’entre eux présentaient un SMet. Les participants présentant un SMet avaient des taux de LBP significativement plus élevés que les autres (25,9 μg/mL et 22,2 μg/mL respectivement). Plus précisément, des taux plus élevés de LBP étaient observés dans 4 des 5 anomalies métaboliques caractéristiques du SMet : obésité abdominale, taux élevé de triglycérides, faible taux d’HDL et hyperglycémie à jeun. Une corrélation positive était observée entre les taux de LBP et de protéine C-réactive (CRP), un marqueur inflammatoire (r2 : 0,56, p < 0,0001). Ajustés sur l’âge, le sexe, le niveau d’éducation, la CRP, le tabagisme, la consommation d’alcool et l’activité physique, un taux plus élevé de LBP était significativement associé à la présence d’un SMet (RC 1,08 IC95 % [1,03–1,13] pour l’augmentation d’1 μg/mL de LBP). La LBP, impliquée dans l’activation du système immunitaire et le déclenchement de processus inflammatoires en réponse aux LPS, pourrait être considérée comme un biomarqueur émergent associé à la présence d’un SMet et de ses anomalies métaboliques, caractéristiques des régimes alimentaires occidentaux riches en lipides, chez la personne âgée.

BACKGROUNDThere is growing evidence that the Mediterranean (Medi) diet may lower the risk of type 2 diabetes mellitus (T2DM). Whether this association is due to the Medi diet by itself or is mediated by a diet -associated lower rate of overweight is uncertain. Our aim was to disentangle these relationships among UK adults.METHODSBased on 21 585 participants from the UK Biobank cohort, the adherence to the Medi diet (high fruits, vegetables, legumes, cereals, fish, olive oil; low meat, dairy products; and intermediate alcohol intakes) was assessed (range 0-18). Data on diabetes were self-reported, and overweight was defined as a body mass index (BMI) ≥ 25 kg/m². A mediation analysis was implemented to disentangle the role of overweight in the Medi diet-T2DM relationship.RESULTSThe average baseline Medi diet score was 8.8 [standard deviation (SD) 2.6]. During a mean follow-up of 6.1 years, 473 individuals developed T2DM. A higher adherence to a Medi diet (+1 point) was associated with 14% decreased risk of T2DM [hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.82-0.90]. This association split into an indirect effect of 10%, mediated by lower odds of overweight (HR: 0.90, 95% CI: 0.87-0.92), and a direct effect of the Medi diet of 4% (HR: 0.96, 95% CI: 0.93-0.99), regardless of the effect mediated by overweight.CONCLUSIONSConsidered as a single mediator, reduced overweight mainly contributes to the association between greater Medi diet adherence and lower risk of T2DM on this British subsample. However, the direct effect of the diet on the risk of T2DM, even weaker, should not be overlooked.

Épidémiologie. Au cours des dernières décennies, l’incidence du diabète de type II (DT2) a augmenté de manière significative à travers le monde, entrainant une augmentation de la morbidité et de la mortalité associées. En termes de prévention, les preuves s’accumulent quant à l’association entre l’adhérence à un régime de type Méditerranéen et un moindre risque de DT2. Dans cette étude, nous nous sommes intéressés à l’effet potentiellement médiateur de l’indice de masse corporelle (IMC) en tant que mécanisme sous-jacent à cette relation. Les participants de la UK Biobank ayant des données cliniques sur le statut diabétique et ayant répondu à au moins un questionnaire nutritionnel ont été inclus. Le statut diabétique était auto-déclaré et les participants ayant un diagnostic de diabète prévalent, gestationnel ou incertain (ç.à.d. variant au cours des suivis) ont été exclus. Le score MEDAS a été utilisé pour évaluer l’adhérence à un régime de type Méditerranéen à l’inclusion, basé sur les seuils de consommation de 11 groupes d’aliments (huile d’olive, légumes, fruits, viande rouge, beurre ou crème, boissons sucrées, vin, légumineuses, poisson, pâtisseries et noix) ainsi qu’une question additionnelle sur la consommation préférentielle de viande rouge ou blanche. Une analyse de médiation causale basée sur un modèle de Cox à risques proportionnels a été utilisé pour évaluer les relations entre MEDAS score et risque de DT2. L’échantillon d’étude était composé de 6362 participants, dont 113 ont développé un diabète incident durant une période de suivi moyenne de 4,6 ans. À l’inclusion, le score MEDAS moyen était de 4,6, variant de 0 à 11. Concernant l’effet total, l’incidence de DT2 était réduite de 12 % chez les participants ayant un score MEDAS plus élevé. Cependant, l’effet direct du score MEDAS sur le risque de DT2 n’était pas significatif après ajustement sur les potentiels facteurs de confusion dont l’IMC (RR 0,91 IC 95 % [0,82–1,02]). Les analyses de médiation ont suggéré que l’IMC expliquait environ 3 % de l’effet du score MEDAS sur le risque de diabète (RR 0,97 IC 95 % [0,96–0,97]). Les effets bénéfiques, et désormais bien connus, d’une plus grande adhérence à un régime de type Méditerranéen sur le risque de DT2 pourraient en partie être médiés par la modulation de l’IMC chez les participants de la UK Biobank.

The gut microbiota is considered to be the main reservoir for pro-inflammatory lipopolysaccharide (LPS)-type endotoxins, and its disruptions have been suspected to be involved in central nervous system disorders, such as Alzheimer's disease (AD). Beneficial to the host when LPS is maintained in the gastrointestinal tract, gut microbiota dysbiosis could lead to increased translocation of the LPS across the intestinal barriers to end up in the bloodstream. However, the role of plasma endotoxemia, which has been defined as the presence of LPS in the bloodstream, in the pathogenesis of AD has not been thoroughly elucidated to date. In a nested case-control study, we evaluated the association between baseline plasma endotoxemia, which was assessed by measuring LPS-Binding Protein (LBP) and soluble Cluster of Differentiation-14 (sCD14) levels, inflammation, which was assessed by Interleukin-6 (IL6) levels, and the odds of developing AD over 12 years. Selected from a population-based cohort, 212 AD incident cases were matched on age, gender and educational level to 424 controls without dementia. Adjusting for a large set of confounders, including anti-inflammatory drugs, higher LBP levels were significantly associated with 30% higher odds of developing AD over 12 years (OR 1.30 95%CI [1.07 - 1.59]), independent of the IL6 levels. No association was found between sCD14, the soluble part of the CD14 receptor, or IL6 and AD. This large case-control study on the association between plasma endotoxemia and AD among elderly community-dwellers provides further potential pathways to investigate for the understanding of AD mechanisms. These results warrant further investigation.

Background: Identifying the mechanisms involved in the pathogenesis of Alzheimer's disease (AD) remains crucially important. Chronic age-related low-grade inflammation is considered to be one such mechanism, although its causes are unclear. Lipopolysaccharide (LPS)-type endotoxins, a major component of the outer membrane of Gram-negative bacteria, are known as potent pro-inflammatory molecules. Therefore, we hypothesized that greater exposure to circulating LPS, potentially mediated by the inflammatory pathway, would be a key step of the onset of AD. Objective: The aim of this study was to investigate the link between plasma endotoxin-exposure, inflammation, and AD. Methods: Applying a nested case-control design, we evaluated the associations among baseline plasma endotoxin-exposure (assessed by measuring LPS-binding protein (LBP) and soluble cluster of differentiation-14 (sCD14) levels), inflammation (assessed by measuring interleukin-6 (IL6) levels), and the odds of developing AD over 12 years. Selected from a population-based cohort, 212 incident cases of AD were matched with 424 controls without dementia with regard to age, gender, and education level. Results: After adjusting for a large set of confounders, including the use of anti-inflammatory drugs, only higher LBP levels were significantly associated with a 30% higher odds of developing AD over 12 years (OR 1.30, 95%CIs [1.07-1.59]), regardless of IL6 levels. Conclusion: This large case-control study provides preliminary results concerning plasma endotoxin-exposure among the elderly and suggests that higher LBP levels, an acute-phase reactant involved in the pro-inflammatory response to LPS, are associated with higher odds of developing AD.

(1) Background: Nutrition is a major lifestyle factor that can prevent the risk of cognitive impairment and dementia. Diet-induced metabolic endotoxemia has been proposed as a major root cause of inflammation and these pathways emerge as detrimental factors of healthy ageing. The aim of this paper was to update research focusing on the relationship between a fat-rich diet and endotoxemia, and to discuss the potential role of endotoxemia in cognitive performances. (2) Methods: We conducted a non-systematic literature review based on the PubMed database related to fat-rich meals, metabolic endotoxemia and cognitive disorders including dementia in humans. A total of 40 articles out of 942 in the first screening met the inclusion criteria. (3) Results: Evidence suggested that a fat-rich diet, depending on its quality, quantity and concomitant healthy food components, could influence metabolic endotoxemia. Since only heterogeneous cross-sectional studies are available, it remains unclear to what extent endotoxemia could be associated or not with cognitive disorders and dementia. (4) Conclusions: A fat-rich diet has the capability to provide significant increases in circulating endotoxins, which highlights nutritional strategies as a promising area for future research on inflammatory-associated diseases. The role of endotoxemia in cognitive disorders and dementia remains unclear and deserves further investigation.

The chemokine CCL11 has been implicated in age-related cognitive deterioration in mice, yet evidence on the relationship between CCL11 and cognitive function in humans is limited. This study explored associations between CCL11 and cognition in rural and urban community-dwelling older adults. Participants were 515 urban dwellers from the 3C-Bordeaux cohort and 318 rural dwellers from the AMI cohort. Plasma CCL11 was measured using an enzyme-linked immunoassay. Mini Mental State Examination (MMSE) test scores were used as the main measure of cognitive performance. Multivariate regression analysis was used to evaluate the cross-sectional association between CCL11 and cognitive performance. CCL11 was significantly higher in rural dwellers compared to city dwellers (median [IQR]: 145 [115-201] pg/mL vs. 103 [85-129] pg/mL; p < 0.001). After adjustment for confounders, CCL11 was found to be negatively associated with cognitive performance in rural dwellers but not in city dwellers. These results suggest that CCL11 may be an independent determinant of cognitive function in older rural dwellers and that the residential environment modifies this association.

Background Frailty in aging populations is associated with increasing evidence of ill health, functional loss, increasing dependency and premature death. The FRAILOMIC Initiative was designed to define, predict and prevent frailty by means of identifying omic markers associated with the diagnosis, risk, and prognosis of frailty. The project hopes to build the foundations for a consensus towards a single operative, clinical definition of frailty to guide the development of ready-to-use kits measuring biomarkers to facilitate frailty risk prediction and improve diagnostic accuracy of frailty in clinical practice. Aims We review current models of frailty, describe the design of the FRAILOMIC study, and discuss the advent of the concept of intrinsic capacity as influencing the science of frailty and how this can be clinically interpreted. Methods Two main frailty models (Fried Phenotype model; Cumulative Deficit Model) are described and evaluated by detailed literature review. A description of the exploratory phase of the FRAILOMIC initiative is given which resulted in the identification of 13 omic markers related to frailty: these are currently being validated in a validation phase. We then discuss how combining the characteristics of frailty with omic-based biomarkers will enable the development of predictive, diagnostic and prognostic models. Conclusions Relating biomarkers associated with frailty to a continuous measure of intrinsic capacity will help in identifying and monitoring at-risk populations. The FRAILOMIC Initiative will provide key insights into the prevention, early detection, and treatment of frailty to reduce the impact of disability in our aging populations.