ObjectivesGut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.DesignWe performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.ResultsSevere obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.

Abstract Host–microbial co-metabolism products are being increasingly recognised to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host–microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach. This work aimed to explore the associations between host plasma metabolomic signatures and gut microbiota composition in healthy adults of the Milieu Intérieur study. For 846 subjects, gut microbiota composition was profiled through sequencing of the 16S rRNA gene in stools. Metabolomic signatures were generated through proton NMR analysis of plasma. The associations between metabolomic variables and α- and β-diversity indexes and relative taxa abundances were tested using multi-adjusted partial Spearman correlations, permutational ANOVA and multivariate associations with linear models, respectively. A multiple testing correction was applied (Benjamini–Hochberg, 10 % false discovery rate). Microbial richness was negatively associated with lipid-related signals and positively associated with amino acids, choline, creatinine, glucose and citrate (−0·133 ≤ Spearman’s ρ ≤ 0·126). Specific associations between metabolomic signals and abundances of taxa were detected (twenty-five at the genus level and nineteen at the species level): notably, numerous associations were observed for creatinine (positively associated with eleven species and negatively associated with Faecalibacterium prausnitzii). This large-scale population-based study highlights metabolites associated with gut microbial features and provides new insights into the understanding of complex host–gut microbiota metabolic relationships. In particular, our results support the implication of a ‘gut–kidney axis’. More studies providing a detailed exploration of these complex interactions and their implications for host health are needed.

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease.

Objective: Dietary indexes measure the adherence of individuals to a set of nutritional recommendations. However, the health gains associated with adherence to various dietary indexes may vary. Our objective was to compare the magnitude of estimated avoided deaths by chronic diseases obtained by improving diet quality in the French population, measured by a variety of dietary indexes. Design: Simulation study based on observational data. Setting: Weighted data from a French population-based cohort study. Participants: In participants from the NutriNet-Sante cohort, we computed dietary scores reflecting the adherence to various recommendations (Medi-Lite, Healthy Diet Indicator (HDI), Programme National Nutrition Sante/National Nutrition and Health Program - Guidelines Score, Diet Quality Index (DQI), Alternative Healthy Eating Index (AHEI) and the modified Food Standards Agency nutrient profiling system dietary index (FSAm-NPS DI)). Quintiles of the food groups' consumption and dietary intakes were used as input in a simulation model (Preventable Risk Integrated ModEl (PRIME)), yielding the number of delayed or avoided deaths in nutrition-related non-communicable diseases, comparing between very high or very low nutritional quality of the diet and medium nutritional quality. Results: A modification of dietary intakes from medium quality to very low quality (i.e. from the middle quintile to the quintile with the lowest nutritional quality) was associated with an increased number of deaths ranging from 3485 (95 % uncertainty interval (CI) 4002, 2987) for HDI and 3379 (95 % CI 3881, 2894) for FSAm-NPS DI to 838 (95 % CI 1163, 523) for Medi-Lite. Conversely, a modification of dietary intakes from medium quality to very high quality was associated with a decrease in the number of deaths ranging from 1995 (95 % CI 1676, 2299) for Probability of Adequate Nutrient intake diet, 1986 (95 % CI 1565, 2361) for DQI-International, 1931 (95 % CI 1499, 2316) for FSAm-NPS DI and 858 (95 % CI 499, 1205) for HDI. Conclusions: Our results provide some insights as the potential impact of following various dietary guidelines to reduce mortality from nutrition-related diseases.

Microbiome community typing analyses have recently identified the Bacteroides 2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans 1 , 2 . Bact2 is characterized by a high proportion of Bacteroides , a low proportion of Faecalibacterium and low microbial cell densities 1 , 2 , and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease 2 . Reported changes in stool consistency 3 and inflammation status 4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort ( n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset ( n = 282) and the independent Flemish Gut Flora Project population cohort ( n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20412-9.

Background: Diet is widely recognized as one of the main modifiable drivers of gut microbiota variability, and its influence on microbiota composition is an active area of investigation. Objective: The present work aimed to explore the associations between usual diet and gut microbiota composition in a large sample of healthy French adults. Methods: Gut microbiota composition was established through sequencing of the 16S rRNA gene in stool samples from 862 healthy French adults of the Milieu Interieur study. Usual dietary consumptions were determined through the administration of a food-frequency questionnaire. The associations between dietary variables and alpha- and beta-diversity indexes and relative taxa abundances were tested using Spearman correlations, permutational ANOVAs, and multivariate analyses with linear models, respectively. Results: Foods generally considered as healthy (raw fruits, fish) were positively associated with alpha-diversity, whereas food items for which a limited consumption is generally recommended (fried products, sodas or sugary drinks, fatty sweet products, processed meats, ready-cooked meals, and desserts) were negatively associated with alpha-diversity. Fruits, fried products, ready-cooked meals, and cheese contributed to shifts within microbiota composition (beta-diversity). Our results also highlighted a number of associations between various food group intakes and abundances of specific phyla, genera, and species. For instance, the consumption of cheese was negatively associated with Akkermansia muciniphila abundance. Conclusions: This large-scale population-based study supports that the usual consumption of certain food items is associated with several gut microbial features, and extends the mechanistic arguments linking Western diet to an altered microbiota composition. These results provide new insights into the understanding of complex diet-gut microbiota relations, and their implications for host health deserve further investigation because altered microbiota diversity was consistently linked to increased risk of several health outcomes. This trial was registered at clinicaltrials.gov as NCT01699893.

A growing number of studies have explored overall health during ageing in a holistic manner by investigating multidimensional models of healthy ageing (HA). However, little attention has been given to the role of adherence to national nutrition guidelines in that context. This study aimed to investigate the prospective association between adherence to the French nutrition guidelines and HA. The authors analysed data from 21 407 participants of the NutriNet-Santé study with a median baseline age of 55·6 years (2009-2014) and initially free of major chronic diseases. HA was defined as not developing major chronic disease, no depressive symptoms, no function-limiting pain, independence in instrumental activities of daily living, good physical, cognitive and social functioning, as well as good self-perceived health. Adherence to guidelines of the French Nutrition and Health Programme (Programme National Nutrition Santé or PNNS) was measured via the PNNS Guideline Score (PNNS-GS), using baseline data from repeated 24-h dietary records and physical activity questionnaires. After a median follow-up of 5·7 years, 46·3 % of participants met our HA criteria. Robust-error-variance Poisson regression revealed that higher PNNS-GS scores, reflecting higher adherence to nutrition recommendations (including both diet and physical activity guidelines), were associated with a higher probability to age healthily (relative riskquartile 4 v. quartile 1 = 1·17 (95 % CI 1·12, 1·22)). Supplementary analyses revealed that this association may, to a small part, be mediated by weight status. The results suggest that high adherence to the French national nutrition recommendations may be linked to better overall health throughout ageing.

Épidémiologie. La littérature scientifique concernant le lien entre les apports en acides gras mono- et polyinsaturés est abondante, mais les résultats sont inconsistants. Notre objectif était d’étudier l’association entre les apports en acides gras insaturés au milieu de la vie et le fonctionnement cognitif mesuré 13 ans plus tard, et d’évaluer un effet modulateur potentiel d’une supplémentation en antioxydants. Les apports en acides gras étaient estimés en utilisant des rappels alimentaires de 24 h répétés (1994–1996), chez 3362 participants (âge moyen ± déviation standard : 65,5 ± 5,6 ans) de l’étude SU.VI.MAX (SUpplémentation en VItamines et Minéraux AntioXydants). L’étude SU.VI.MAX incluait une phase d’intervention (1994–2002) pendant laquelle les participants étaient attribués, de manière randomisée, à un groupe « supplémentation en antioxydants à doses nutritionnelles » ou à un groupe placebo. Le supplément, reçu chaque jour entre 1994 et 2002, était composé d’une combinaison de 120 mg de vitamine C, 30 mg de vitamine E, 6 mg de bêta-carotène, 100 μg de sélénium et 20 mg de zinc. Le fonctionnement cognitif était évalué uniquement à la fin du suivi (2007–2009), par une batterie de 6 tests neuropsychologiques. Un score cognitif global a été créé en calculant la somme de t-scores de ces 6 tests. Des modèles d’analyse de covariance (ANCOVA) ajustés sur les facteurs confondants potentiels ont été utilisés afin de calculer des différences moyennes ajustées du score cognitif global entre tertiles des apports en acides gras. Dans ces modèles multivariables, les apports en acides gras monoinsaturés (AGMI) totaux, polyinsaturés (AGPI) totaux, et polyinsaturés n-6 étaient positivement associés avec le fonctionnement cognitif global. Les acides gras polyinsaturés n-3 montraient des relations positives avec le fonctionnement cognitif uniquement chez les participants supplémentés en antioxydants (différence moyenne tertile3 versus tertile1 = 1,40 ; intervalle de confiance à 95 % = 0,30, 2,51, Ptrend = 0,01, Pinteraction = 0,01). Un moins bon fonctionnement cognitif global a été observé chez les sujets présentant des apports plus élevés en acide arachidonique uniquement au sein du groupe placebo (différence moyenneTertile3 versus Tertile1 = − 1,38 ; intervalle de confiance à 95 % = − 2,57, − 0,18, Ptrend = 0,02, Pinteraction = 0,07). Des apports élevés en AGMI totaux et en AGPI n-6 pourraient être bénéfiques pour maintenir une bonne santé cognitive au cours du vieillissement, des apports plus élevés en AGPI n-3 pourraient être bénéfiques seulement chez des individus ayant un statut adéquat en antioxydants. Ces résultats soulignent l’importance de ne pas seulement cibler des nutriments spécifiques dans le cadre de la prévention de démences, mais de considérer l’interaction complexe entre les nutriments consommés.

Epidémiologie. Le co-métabolisme hôte-microbiote est à l’origine d’un très grand nombre de molécules intégrées au sein d’axes métaboliques complexes. De nombreuses études se sont attachées à la caractérisation fonctionnelle spécifique de certaines de ces molécules (AGCC, BCAA, TMAO, etc.), mais les études envisageant plus globalement les relations métaboliques entre l’hôte et son microbiote intestinal restent rares. À ce titre, l’étude globale des métabolites endogènes et exogènes présents dans le plasma par métabolomique non ciblée semble prometteuse. L’objectif de cette étude était de caractériser les associations entre profils métabolomiques plasmatiques et composition du microbiote intestinal dans une population d’adultes en bonne santé. La composition du microbiote intestinal a été déterminée dans les selles (séquençage du gène ARNr16S, les matrices de Jaccard et Bray-Curtis ont été déterminées) et les profils métabolomiques ont été générés en utilisant les séquences RMN CPMG et NOESY sur des échantillons de plasma, chez 846 individus de la population Milieu Intérieur. La co-structure globale des données 16S et RMN a été évaluée par co-inertie. Les associations entre variables métabolomiques d’une part et matrices de β-diversité ou abondance des taxons d’autre part ont été calculées par PERMANOVA ou MaAsLin ajustés sur le sexe, l’âge, l’IMC, le statut tabagique et l’activité physique (PERMANOVA également ajustées sur la profondeur de séquençage). Une correction de Benjamini-Hochberg (FDR-10 %) a été appliquée. La co-inertie globale des données microbiote et métabolomique était limitée (RV ≤ 0,05). En revanche, des associations spécifiques ont été détectées. Les matrices de Jaccard et de Bray-Curtis étaient significativement et respectivement associées à 51 et 3 variables CPMG, dont certaines ont d’ores et déjà été identifiées (pyruvate, tyrosine, choline, glucose, etc.). Des associations entre le pyruvate et 3 genres bactériens (positives avec Catabacter et Acholeplasma, négative avec Faecalibacterium) ont été mises en évidence. L’analyse des associations entre variables métabolomiques NOESY et données microbiote 16S, et l’identification des métabolites discriminants sont en cours. Ces résultats préliminaires permettent de mettre en évidence des associations entre le profil métabolomique RMN déterminé sur le plasma de l’hôte et la composition du microbiote intestinal. Toutefois, cette étude ne permet pas de conclure sur une potentielle relation causale, et d’autres études sont nécessaires.

Introduction and purpose of the study: Host-microbiotic co-metabolism is at the origin of a very large number of molecules integrated within complex metabolic axes. Many studies have focused on the specific functional characterization of some of these molecules (AGCC, BCAA, TMAO, etc.), but studies looking more generally at metabolic relationships between the host and its gut microbiota remain rare. As such, the global study of endogenous and exogenous metabolites present in plasma by non-targeted metabolomics seems promising. The objective of this study was to characterize associations between plasma metabolomic profiles and gut microbiota composition in a healthy adult population. Material and methods: The composition of the gut microbiota was determined in the stool (sequencing of the 16S rRNA gene, the Jaccard and Bray-Curtis matrices were determined) and the metabolomic profiles were generated using the CPMG and NOESY NMR sequences on plasma samples, in 846 individuals of the population Internal Medium. The overall co-structure of 16S and NMR data was evaluated by co-inertia. Associations between metabolomic variables on the one hand and matrices of β-diversity or abundance of taxa on the other hand were calculated by PERMANOVA or MaAsLin adjusted for sex, age, BMI, smoking status and activity. physical (PERMANOVA also adjusted to the depth of sequencing). A Benjamini-Hochberg correction (FDR-10%) was applied. Results and Statistical Analysis: Overall co-inertia of microbiota and metabolomic data was limited ( RV ≤ 0.05). In contrast, specific associations were detected. The Jaccard and Bray-Curtis matrices were significantly and respectively associated with 51 and 3 CPMG variables, some of which have already been identified (pyruvate, tyrosine, choline, glucose, etc.). Associations between pyruvate and 3 bacterial genera (positive with Catabacter and Acholeplasma, negative with Faecalibacterium ) were highlighted. Analysis of associations between NOESY metabolomic variables and 16S microbiota data, and the identification of discriminant metabolites are ongoing. Conclusion: These preliminary results make it possible to demonstrate associations between the NMR metabolomic profile determined on the host plasma and the composition of the intestinal microbiota. However, this study does not conclude on a potential causal relationship, and further studies are needed.

Ultra-processed food (UPF) consumption has increased over the last decades in Westernized countries. Our objective was to investigate for the first time the association between the proportion of UPF (%UPF) in the diet and incident depressive symptoms in the NutriNet-Santé cohort. The sample included 20,380 women and 6350 men (aged 18–86 years) without depressive symptoms at the first Center for Epidemiologic Studies Depression Scale (CES-D) measurement, using validated cut-offs (CES-D score ≥ 17 for men and ≥ 23 for women). The proportion of UPF in the diet was computed for each subject using the NOVA classification applied to dietary intakes collected by repeated 24-h records (mean = 8; SD = 2.3). The association between UPF and depressive symptoms was evaluated using multivariable Cox proportional hazards models. Over a mean follow-up of 5.4 years, 2221 incident cases of depressive symptoms were identified. After accounting for a wide range of potential confounders, an increased risk of depressive symptoms was observed with an increased %UPF in the diet. In the main model adjusted for sociodemographic characteristics, body mass index, and lifestyle factors, the estimated hazard ratio for a 10% increase in UPF was 1.21 (95% confidence interval = 1.15–1.27). Considering %UPF in food groups, the association was significant only for beverages and sauces or added fats. Overall, UPF consumption was positively associated with the risk of incident depressive symptoms, suggesting that accounting for this non-nutritional aspect of the diet could be important for mental health promotion.

Épidémiologie. Il a été suggéré que l’inflammation (pouvant être modulée par l’alimentation) joue un rôle important dans l’étiologie de la dépression, mais les études prospectives portant sur l’association entre le potentiel inflammatoire du régime alimentaire et la dépression en population générale sont limitées. L’objectif de la présente étude était donc d’examiner l’association prospective entre le potentiel inflammatoire du régime alimentaire et le risque de symptômes dépressifs dans une population d’adultes français. L’étude a porté sur un échantillon de 26 730 hommes et femmes (âgés de 18 ans ou plus) de la cohorte NutriNet-Santé, qui avaient des données alimentaires valides, avaient rempli le questionnaire Center for Epidemiologic Studies-Depression Scale (CES-D) au moins 2 fois au cours du suivi (avec un maximum de 3 points disponibles par participant) et qui n’avaient pas de symptômes dépressifs lors de la première évaluation de la symptomatologie dépressive (CES-D < 17 pour les hommes et < 23 pour les femmes). Les cas incidents de symptômes dépressifs étaient les participants qui présentaient des symptômes dépressifs au moins une fois au cours du suivi. Le potentiel inflammatoire du régime alimentaire a été mesuré à l’aide d’une version alternative du Dietary Inflammatory Index original, nommée Alternate Dietary Inflammatory Index (ADII), un score élevé reflétant une alimentation pro-inflammatoire. Les associations entre l’ADII et le risque de symptômes dépressifs ont été évaluées à l’aide des ratios de risques instantanés (HR) et leurs intervalles de confiance (IC) à 95 %, estimés en utilisant des modèles de Cox à risque proportionnel pour les données censurées par intervalles. Au cours du suivi, 2221 cas de symptômes dépressifs incidents ont été identifiés. Après ajustement sur différents facteurs de confusion potentiels, les participants qui étaient dans le quatrième quartile de l’ADII (reflétant un régime alimentaire plus « pro-inflammatoire ») avaient 15 % (IC à 95 %= 2 %–31 %) de plus de risque de développer des symptômes dépressifs, comparés aux participants qui étaient dans le premier quartile. Un effet modulateur de l’indice de masse corporelle (IMC < 25 vs ≥ 25 kg/m2) a été observé, avec des associations qui n’étaient significatives que chez les participants présentant un IMC ≥ 25 (HR = 1,29 ; IC à 95 %= 1,04–1,60). Les résultats de cette étude suggèrent que la promotion d’une alimentation « saine » présentant des propriétés anti-inflammatoires est importante pour la prévention des symptômes dépressifs, en particulier chez les personnes présentant un IMC supérieur au seuil de 25.

Our objective was to examine whether adherence to the Mediterranean–DASH diet intervention for neurodegenerative delay (MIND) was associated with SMC (as measured by the cognitive difficulties scale; CDS) in the NutriNet-Santé cohort.

BACKGROUND:Low-grade chronic inflammation has been suggested to play a substantial role in the etiology of depression; however, studies on the prospective association between the inflammatory potential of the diet and depression are limited.OBJECTIVE:The aim of this study was to investigate the association between the inflammatory potential of the diet (measured using the Alternate Dietary Inflammatory Index, ADII) and incident depressive symptoms. We also tested the potential modulating effect of sex, age, BMI, and lifestyle indicators.METHODS:The study sample consisted of 26,730 participants (aged 18-86 y) from the NutriNet-Santé study. Baseline ADII was computed using repeated 24-h dietary records collected during the first 2 y of the follow-up. Incident cases of depressive symptoms were defined by a Center for Epidemiologic Studies Depression scale ≥17 for men and ≥23 for women at least once during follow-up. HR and 95% CI were estimated using multivariable Cox proportional hazards models.RESULTS:A total of 2221 incident cases of depressive symptoms were identified over a mean follow-up of 5.4 y. After accounting for a wide range of potential confounders, the highest quartile of the ADII was associated with a 15% (95% CI: 2, 31) increase in the risk of depressive symptoms compared with the lowest quartile. In the stratified analyses, associations were statistically significant only among women (HRquartile4 vs. quartile1: 1.19; 95% CI: 1.02, 1.37), middle-age adults (HRquartile4 vs. quartile1: 1.16; 95% CI: 1.00, 1.35), and participants with a BMI ≥25 (HRquartile4 vs. quartile1: 1.29; 95% CI: 1.04, 1.60).CONCLUSIONS:Overall, a proinflammatory diet was associated with a higher risk of depressive symptoms, especially among women, middle-age adults, and participants with overweight or obesity. These findings contribute to the increasing scientific evidence showing a detrimental role of the proinflammatory diet. The NutriNet-Santé study is registered at clinicaltrials.gov as NCT03335644.

A posteriori healthier dietary patterns and several nutrients have been associated with lower risks of depression in various studies; however, evidence is lacking with regard to the prospective association between adherence to nutritional recommendations (food-based and nutrient-based recommendations) and incident depression or depressive symptoms. In this study, we investigate such associations in the NutriNet Santé cohort. The study sample included 26 225 participants (aged 18-86 years) who were initially free of depressive symptoms. Adherence to nutritional recommendations was measured by four scores namely modified French Programme National Nutrition Santé-Guideline Score (mPNNS-GS), Alternative Healthy Eating Index-2010 (AHEI-2010), Probability of Adequate Nutrient Intake Dietary Score (PANDiet) and Diet Quality Index-International (DQI-I), using non-consecutive dietary record data during the first 2 years of follow-up (mean number of recording days=8, sd 2). Depressive symptoms were defined by a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥17 for men and ≥23 for women. We used Cox proportional hazards models to estimate hazard ratios and 95 % CI, modelling the dietary scores as standardised continuous variables and as tertiles. Over a mean follow-up of 6 years, we identified 2166 incident cases of depressive symptoms. All dietary scores with the exception of the AHEI-2010 were significantly inversely associated with incident depressive symptoms. In the fully adjusted model, an increase of 1 sd in the mPNNS-GS, PANDiet and DQI-I was, respectively, associated with an 8 % (95 % CI 4, 13), 5 % (95 % CI 1, 9) and 9 % (95 % CI 5, 13) reduction in the risk of depressive symptoms. Overall, these findings suggest that diet in accordance with national or international guidelines could have beneficial effects with regard to mental health.

Obesity and its metabolic complications are characterized by subclinical systemic and tissue inflammation. In rodent models of obesity, inflammation and metabolic impairments are linked with intestinal barrier damage. However, whether intestinal permeability is altered in human obesity remains to be investigated. In a cohort of 122 severely obese and non-obese patients, we analyzed intestinal barrier function combining in vivo and ex vivo investigations. We found tight junction impairments in the jejunal epithelium of obese patients, evidenced by a reduction of occludin and tricellulin. Serum levels of zonulin and LPS binding protein, two markers usually associated with intestinal barrier alterations, were also increased in obese patients. Intestinal permeability per se was assessed in vivo by quantification of urinary lactitol/mannitol (L/M) and measured directly ex vivo on jejunal samples in Ussing chambers. In the fasting condition, L/M ratio and jejunal permeability were not significantly different between obese and non-obese patients, but high jejunal permeability to small molecules (0.4 kDa) was associated with systemic inflammation within the obese cohort. Altogether, these results suggest that intestinal barrier function is subtly compromised in obese patients. We thus tested whether this barrier impairment could be exacerbated by dietary lipids. To this end, we challenged jejunal samples with lipid micelles and showed that a single exposure increased permeability to macromolecules (4 kDa). Jejunal permeability after the lipid load was two-fold higher in obese patients compared to non-obese controls and correlated with systemic and intestinal inflammation. Moreover, lipid-induced permeability was an explicative variable of type 2 diabetes. In conclusion, intestinal barrier defects are present in human severe obesity and exacerbated by a lipid challenge. This paves the way to the development of novel therapeutic approaches to modulate intestinal barrier function or personalize nutrition therapy to decrease lipid-induced jejunal leakage in metabolic diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background:While low-grade chronic inflammation has been suggested as a major modulator of healthy aging (HA), no study has yet investigated the link between the inflammatory potential of the diet and multidimensional concepts of HA.Objective:We aimed to evaluate the association between the inflammatory potential of the diet at midlife, as measured by the Dietary Inflammatory Index (DII), and HA assessed 13 y later.Methods:We analyzed data from 2796 participants in the French Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study aged 45-60 y at baseline (1994-1995) and initially free of diabetes, cardiovascular disease, and cancer. During the trial phase of the study (1994-2002), participants received either a placebo or a daily nutritional dose of antioxidant supplement (120 mg vitamin C, 6 mg β-carotene, 30 mg vitamin E, 100 μg Se, 20 mg Zn). HA was assessed in 2007-2009, and defined as having no major chronic disease, good physical and cognitive functioning, independence in daily activities, no depressive symptoms, good social health, good overall self-perceived health, and no function-limiting pain. The DII was calculated based on repeated baseline 24-h dietary records. Its association with HA was assessed by robust-error-variance Poisson regression, providing RR estimates.Results:After adjustment for potential confounders, higher DII scores (reflecting a more proinflammatory diet), were associated with a decreased likelihood of HA: RRtertile 3/tertile 1 = 0.85 (95% CI: 0.74, 0.99); P-trend = 0.03. Secondary analyses revealed that this association was only significant among participants who had been in the placebo group during the trial phase: RRtertile 3/tertile 1 = 0.80 (95% CI: 0.64, 1.00); P-trend = 0.04.Conclusions:This study suggests that a proinflammatory diet may lower the probability of overall HA. The SU.VI.MAX trial was registered at www.clinicaltrials.gov as NCT00272428.

Background: Our objective was to quantify to what extent the association between adherence to the French nutritional recommendations at midlife, measured by the Programme National Nutrition Santé-Guideline Score (PNNS-GS), and healthy aging (HA) is mediated by body mass index (BMI) status. Methods: We analyzed data from 2249 participants of the French ‘Supplementation with Vitamins and Mineral Antioxidants’ (SU.VI.MAX-‘SUpplémentation en VItamines et Minéraux AntioXydants’) cohort. At baseline (1994–1995), data on BMI status (<25 vs. ≥25 and <30 vs. ≥30) and diet were collected. At follow-up (2007–2009), HA status (yes/no) was evaluated via a multidimensional concept focusing on chronic disease incidence, physical and cognitive functioning, mental and social health, pain, and perceived health. Relative risks (RR) were estimated by extensively adjusted robust-error-variance Poisson regression, and counterfactual-based mediation analysis was performed. Results: Our HA criteria were met by 39% of participants. We identified a positive direct relation of a greater adherence to the French nutritional recommendations, with the probability of HA (RRQuartile 4 vs. quartile 1 = 1.31 (95% confidence interval (CI) = 1.13, 1.53)), and an indirect relation mediated by BMI status (1.01 (95% CI: 1.01, 1.02)), accounting for 5% of the total relation. Conclusion: These results indicate that high dietary quality may contribute to the preservation of overall health during aging, partly via obesity prevention and partly via other mechanisms.

Background: Several modifiable lifestyle indicators, including diet, smoking, alcohol consumption, weight and physical activity have been associated with depression; however, their combined effect has been less studied. The aim of this study was to calculate a Healthy Lifestyle Index (HLI) composed of the 5 above-mentioned indicators and investigate its association with incident depressive symptoms. Methods: The study sample consisted of 25,837 participants from the NutriNet-Sante study, initially free of depressive symptoms. The HLI was computed by assigning 1 point to each lifestyle indicator namely healthy diet, healthy weight, moderate or high physical activity, never smoking and low alcohol consumption. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Hazard Ratios were estimated using Cox proportional hazards models and population attributable risks (PAR) were calculated. Results: A total of 2112 incident cases of depressive symptoms were identified over a mean follow-up of 5 years. After accounting for a wide range of potential confounders, a 1-point increase in the HLI was associated with a 10% (95% CI 6%; 13%) reduction in the risk of depressive symptoms. The estimated PAR representing the proportion of cases that are attributable to non-adherence to specific healthy lifestyle indicators were 8% for healthy diet, 5% for healthy weight, 5% for non-smoking and 14% for the non-adherence to a combination of healthy diet, healthy weight and non-smoking. Limitations: Some unmeasured factors related to both depression and lifestyle indicators, such as family history of depressive disorder, stressful life events, and sleep disorders might have led to potential residual confounding. Conclusions: Modifying unhealthy lifestyles, especially diet, weight and smoking, is a potential target of major interest in the prevention of depressive symptoms in adults.