Combinatorial, additive and dose-dependent drug-microbiome associations.

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.

Nourishing the gut: the impact of diet on host-gut microbiota interaction.

PURPOSE OF REVIEW: Understanding the spectrum of drivers that influence the gut microbiome (GM) remains a crucial field of investigation. Among these factors, diet has received particular attention, as it could explain up to 20% of the variability in GM composition between individuals. This review focuses on the complex relationships between different dietary patterns and GM in humans, based on recent findings. RECENT FINDINGS: Current evidence underscores the multifaceted impact of diet on GM richness, diversity, and overall composition. Key contributing factors encompass dietary habits, nutritional interventions, food quality and variety, macronutrient distribution, timing of feeding, and selective exclusion of certain foods. SUMMARY: The intricate interplay between diet and GM is of fundamental importance in shaping the interaction between the host and the environment. Further understanding the causal impact of diet on GM has promising potential for the advancement of strategies to promote health and mitigate cardio-metabolic disease risks through dietary interventions. GRAPHICAL ABSTRACT: http://links.lww.com/COCN/A21.

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.

OBJECTIVES: Gut 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. DESIGN: We 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. RESULTS: Severe 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. CONCLUSION: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity. TRIAL REGISTRATION NUMBER: NCT02059538.

Senescence-associated ß-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity.

AIM/HYPOTHESIS: Altered adipose tissue secretory profile contributes to insulin resistance and type 2 diabetes in obesity. Preclinical studies have identified senescent cells as a cellular source of proinflammatory factors in adipose tissue of obese mice. In humans, potential links with obesity comorbidities are poorly defined. Here, we investigated adipose tissue senescent status and relationships with metabolic complications in human obesity. METHODS: The study includes a prospective cohort of 227 individuals with severe obesity. A photometric method was used to quantify senescence-associated ß-galactosidase (SA-ß-gal) activity in paired subcutaneous and omental adipose tissue biopsies obtained during gastric surgery. Gene and secretory profiling was performed in adipose tissue biopsies and in human primary pre-adipocytes in the presence or absence of senolytic drugs targeting senescent cells. Participants were phenotyped for anthropometric and bioclinical variables, metabolic complications and gastric surgery-induced improvement to address relationships with adipose tissue SA-ß-gal. RESULTS: SA-ß-gal activity was sevenfold higher in subcutaneous than in omental adipose tissue and not associated with BMI or chronological age. Several factors, including insulin-like growth factor binding protein 3 (IGFBP3), plasminogen activator inhibitor 1 (PAI1), C-C motif chemokine ligand 2 (CCL2) and IL-6, were upregulated in subcutaneous adipose tissue in relation with SA-ß-gal (p for linear trend across tertiles <0.05) and in pre-adipocytes cultured with inflammatory macrophage conditioned media. Senolytic treatment reduced SA-ß-gal staining and normalised these alterations. In the whole population, subcutaneous adipose tissue SA-ß-gal activity was positively associated with serum leptin, markers of insulin resistance and increased trunk fat mass. Metabolic complications, including type 2 diabetes and dyslipidaemia, were more prevalent in patients with high levels of SA-ß-gal, but improved with bariatric surgery whatever the initial adipose tissue senescent status. CONCLUSIONS/INTERPRETATION: This study highlights a phenotype of senescence in adipose tissue of severely obese individuals, which characterises prominently subcutaneous fat depots. Subcutaneous adipose tissue senescence is significantly linked to altered glucose metabolism and body fat distribution. Elimination of senescent cells through senolytic treatment could alleviate metabolic complications in severely obese people. Graphical abstract.

Relationship between sensory liking for fat, sweet or salt and cardiometabolic diseases: mediating effects of diet and weight status.

PURPOSE: Previous works have been suggested that individual sensory liking is a predictor of dietary intake and weight status, and may consequently influence development of cardiometabolic diseases (CMDs). We investigated the association between sensory liking for fat-and-salt, fat-and-sweet, sweet or salt and the onset of hypertension, diabetes and cardiovascular diseases (CVDs) over 6 years in adults, and the mediating effects of dietary intake and body mass index (BMI). METHODS: We examined the CMDs risk among 41,332 (for CVD and diabetes) and 37,936 (for hypertension) French adults (NutriNet-Santé cohort). Liking scores, individual characteristics, diet and anthropometry were assessed at baseline using questionnaires. Health events were collected during 6 years. Associations between sensory liking and CMDs risk, and the mediating effect of diet and BMI, were assessed using Cox proportional hazards models. RESULTS: Sensory liking for fat-and-salt was associated with an increased risk of diabetes, hypertension and CVD [hazard ratios (HR) for 1-point increment of the sensory score: HR 1.30 (95% CI 1.18, 1.43), HR 1.08 (1.04, 1.13) and HR 1.10 (1.02, 1.19), respectively]. BMI and dietary intake both explained 93%, 98% and 70%, of the overall variation of liking for fat-and-salt liking in diabetes, hypertension and CVD, respectively. Liking for fat-and-sweet and liking for salt were also associated with an increased risk of diabetes [HR 1.09 (1.01, 1.17) and HR 1.09 (1.01, 1.18), respectively], whereas liking for sweet was associated with a decreased risk [HR 0.76 (0.69, 0.84)]. CONCLUSIONS: Higher liking for fat-and-salt is significantly associated with CMDs risk, largely explained by dietary intake and BMI. Our findings may help to guide effective targeted measures in prevention.

Association of diet quality and physical activity with healthy ageing in the French NutriNet-Santé cohort.

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.

Association between organic food consumption and metabolic syndrome: cross-sectional results from the NutriNet-Santé study.

PURPOSE: Metabolic syndrome (MetS), a multicomponent condition, is a cardiovascular disease predictor. Although exposure to agricultural pesticides has been suggested as a potential contributor to the rising rates of obesity, type 2 diabetes, and other features of metabolic disorders, no studies have focused on the association between consumption of organic food (produced without synthetic pesticides) and MetS. We aimed to investigate the cross-sectional association between organic food consumption and MetS in French adults to determine whether it would be worth conducting further studies, particularly large prospective and randomised trials. METHODS: A total of 8174 participants from the NutriNet-Santé study who attended a clinical visit and completed an organic food frequency questionnaire were included in this cross-sectional analysis. We evaluated the association between the proportion of organic food in the diet (overall and by food group) and MetS using Poisson regression models while adjusting for potential confounders. RESULTS: Higher organic food consumption was negatively associated with the prevalence of MetS: adjusted prevalence ratio was 0.69 (95% CI 0.61, 0.78) when comparing the third tertile of proportion of organic food in the diet with the first one (p value <0.0001). Higher consumption of organic plant-based foods was also related to a lower probability of having MetS. In addition, when stratifying by lifestyle factors (nutritional quality of the diet, smoking status, and physical activity), a significant negative association was detected in each subgroup (p values <0.05), except among smokers. CONCLUSIONS: Our results showed that a higher organic food consumption was associated with a lower probability of having MetS. Additional prospective studies and randomised trials are required to ascertain the relationship between organic food consumption and metabolic disorders.

Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes.

High-protein diets are promoted for individuals with type 2 diabetes (T2D). However, effects of dietary protein interventions on (gut-derived) metabolites in T2D remains understudied. We therefore performed a multi-center, randomized-controlled, isocaloric protein intervention with 151 participants following either 12-week high-protein (HP; 30Energy %, N = 78) vs. low-protein (LP; 10 Energy%, N = 73) diet. Primary objectives were dietary effects on glycemic control which were determined via glycemic excursions, continuous glucose monitors and HbA1c. Secondary objectives were impact of diet on gut microbiota composition and -derived metabolites which were determined by shotgun-metagenomics and mass spectrometry. Analyses were performed using delta changes adjusting for center, baseline, and kidney function when appropriate. This study found that a short-term 12-week isocaloric protein modulation does not affect glycemic parameters or weight in metformin-treated T2D. However, the HP diet slightly worsened kidney function, increased alpha-diversity, and production of potentially harmful microbiota-dependent metabolites, which may affect host metabolism upon prolonged exposure.

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide.

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.

The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.

Protein Intake, Metabolic Status and the Gut Microbiota in Different Ethnicities: Results from Two Independent Cohorts.

BACKGROUND: Protein intake has been associated with the development of pre-diabetes (pre-T2D) and type 2 diabetes (T2D). The gut microbiota has the capacity to produce harmful metabolites derived from dietary protein. Furthermore, both the gut microbiota composition and metabolic status (e.g., insulin resistance) can be modulated by diet and ethnicity. However, to date most studies have predominantly focused on carbohydrate and fiber intake with regards to metabolic status and gut microbiota composition. OBJECTIVES: To determine the associations between dietary protein intake, gut microbiota composition, and metabolic status in different ethnicities. METHODS: Separate cross-sectional analysis of two European cohorts (MetaCardis, n = 1759; HELIUS, n = 1528) including controls, patients with pre-T2D, and patients with T2D of Caucasian/non-Caucasian origin with nutritional data obtained from Food Frequency Questionnaires and gut microbiota composition. RESULTS: In both cohorts, animal (but not plant) protein intake was associated with pre-T2D status and T2D status after adjustment for confounders. There was no significant association between protein intake (total, animal, or plant) with either gut microbiota alpha diversity or beta diversity, regardless of ethnicity. At the species level, we identified taxonomical signatures associated with animal protein intake that overlapped in both cohorts with different abundances according to metabolic status and ethnicity. CONCLUSIONS: Animal protein intake is associated with pre-T2D and T2D status but not with gut microbiota beta or alpha diversity, regardless of ethnicity. Gut microbial taxonomical signatures were identified, which could function as potential modulators in the association between dietary protein intake and metabolic status.

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology.

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.

Combination of Healthy Lifestyle Factors on the Risk of Hypertension in a Large Cohort of French Adults.

BACKGROUND: Healthy lifestyle factors are widely recommended for hypertension prevention and control. Nevertheless, little is known about their combined impact on hypertension, in the general population. Our aim was to compute a Healthy Lifestyle Index (HLI) comprising the main non-pharmacological measures usually recommended to improve hypertension prevention: normal weight, regular physical activity, limited alcohol consumption, adoption of a healthy diet; to evaluate their combined impact on hypertension incidence. METHODS: We prospectively followed the incidence of hypertension among 80,426 French adults participating in the NutriNet-Santé cohort study. Self-reported dietary, socio-demographic, lifestyle and health data were assessed at baseline and yearly using a dedicated website; the association between HLI and hypertension risk was assessed by multivariable Cox proportional hazards models adjusted for age, sex, family history of hypertension, socio-demographic and lifestyle factors. Hypothetical Population Attributable Risks associated to each factor were estimated. RESULTS: During a median follow-up of 3.5 years (IQR: 1.5-5.3), 2413 incident cases of hypertension were identified. Compared with no or one healthy lifestyle factor, the hazard ratios (HR) for hypertension were 0.76 (95% CI, 0.67-0.85) for two factors, 0.47 (95% CI, 0.42-0.53) for three factors and 0.35 (95% CI, 0.30-0.41) for all healthy lifestyle factors (p-trend <0.0001). Compared with adhering to 0, 1, 2 or 3 healthy lifestyles, adhering to all of them was found associated with a reduction of the hypertension risk of half (HR = 0.55 (95% CI, 0.46-0.65)). CONCLUSION: Active promotion of healthy lifestyle factors at population level is a key leverage to fight the hypertension epidemic.

Prospective Association between Total and Specific Dietary Polyphenol Intakes and Cardiovascular Disease Risk in the Nutrinet-Santé French Cohort.

BACKGROUND: Epidemiological and experimental evidence support a protective effect of dietary polyphenols on chronic diseases, but high quality longitudinal data are needed, including details on categories of polyphenols. Our objective was to investigate the prospective association between total and individual classes and subclasses of dietary polyphenols and the risk of major cardiovascular disease in the NutriNet-Santé cohort. METHODS: A total of 84,158 participants, who completed at least three 24 h dietary records, were included between May 2009 and June 2017. Individual polyphenols intakes were obtained by matching food consumption data from the 24 h dietary records with the Phenol-Explorer polyphenol composition database. Multivariable Cox proportional hazards models were used to characterize the associations between dietary polyphenols and the incidence of cardiovascular diseases, comparing tertile T3 vs. T1 of classes and subclasses of polyphenols. RESULTS: Over a median of 4.9 years of follow-up, 602 major cardiovascular events were diagnosed. Intakes of anthocyanins, catechins, and flavonols were strongly inversely associated with cardiovascular disease risk (anthocyanins: Hazard Ratio (HR)for a 1-point increment of 10 mg/day = 0.98 (0.96⁻0.99, p = 0.03, HRT3vs.T1 = 0.66 (0.52⁻0.83), ptrend = 0.0003; catechins: HRfor a 1-point increment of 10 mg/day = 0.98 (0.96⁻0.99), p = 0.02, HRT3vs.T1 = 0.74 (0.60⁻0.91), ptrend = 0.004; flavonols: HRfor a 1-point increment of 10 mg/day = 0.94 (0.90⁻0.99), p = 0.02, HRT3vs.T1 = 0.75 (0.61⁻0.94), ptrend = 0.006). Intakes of dihydrochalcones, proanthocyaninidins, dihydroflavonols, hydroxybenzoic acids, and stilbenes were also associated with a decrease (13%, 19%, 24%, 24%, and 27%, respectively) in cardiovascular disease risk, when comparing tertile T3 to T1. CONCLUSIONS: Higher intakes of polyphenols, especially of anthocyanins, catechins, and flavonols, were associated with a statistically significant decreased cardiovascular disease risk.

[Nutrition and cardiometabolic diseases]. / Rôle de la nutrition dans les maladies cardiométaboliques

Numerous published scientific studies in the field of human nutrition suggest, with mixed levels of evidence, that nutrients, foods, and dietary patterns are major determinants of cardiometabolic diseases. In some cases, the convergence of scientific arguments is such that the scientific community have issued in international consensus nutritional recommendations. In other cases, on the contrary, the arguments available do not yet make it possible to affirm the reality of the link between the suspected nutritional factors and cardiometabolic diseases. This article is based on the state-ofthe- art scientific evidence available to enlighten the reader on the components of a beneficial, deleterious or neutral diet on cardiometabolic health.

De nombreux travaux scientifiques publiés permettent d'affirmer, avec des niveaux de preuve variés, que la nutrition humaine à des degrés différents (nutriments, aliments, typologie alimentaire globale) joue un rôle important dans la survenue des maladies cardiométaboliques. Si dans certains cas, la convergence des arguments scientifiques est telle que cette association fait l'objet d'un consensus international, dans d'autres cas au contraire, assez nombreux, les arguments disponibles ne permettent pas encore d'affirmer la réalité du lien entre le facteur nutritionnel suspecté et les maladies cardiométaboliques.

Individual and Combined Effects of Dietary Factors on Risk of Incident Hypertension: Prospective Analysis From the NutriNet-Santé Cohort.

Dietary intake is pointed as one of the major determinants in hypertension development. Data in the area are mostly obtained from cross-sectional studies. We aimed to investigate the prospective association between (1) individual nutritional factors and (2) adherence to the Dietary Approach to Stop Hypertension and the risk of incident hypertension in a large cohort study. We prospectively examined the incidence of hypertension among 80 426 French adults participating in the NutriNet-Santé cohort study. Self-reported sociodemographic, lifestyle health questionnaires and dietary consumption assessed by three 24-hour records were completed at baseline and yearly thereafter. Associations between quartiles (Q) of nutrients and food groups and adherence to Dietary Approach to Stop Hypertension diet and hypertension risk were assessed by multivariable Cox proportional hazards models. During a mean follow-up of 3.4±2.1 years, 2413 cases of incident hypertension were documented. Dietary intakes of sodium (Q4 versus Q1): hazard ratio (HR)=1.17 (95% confidence interval [CI], 1.02-1.35), potassium: HR=0.82 (95% CI, 0.72-0.94), animal protein: HR=1.26 (95% CI, 1.11-1.43), vegetable protein: HR=0.85 (95% CI, 0.75-0.95), fiber: HR =0.81 (95% CI, 0.71-0.93), magnesium: HR=0.77 (95% CI, 0.67-0.89), fruit and vegetables: HR=0.85 (95% CI, 0.74-0.97), whole grain: HR=0.84(95% CI, 0.76-0.93), nuts: HR=0.72 (95% CI, 0.63-0.83), and red and processed meat: HR=1.25 (95% CI, 1.11-0.42) were associated with risk of hypertension. Besides, adherence to the Dietary Approach to Stop Hypertension was strongly inversely associated with incident hypertension: (Q4 versus Q1) HR=0.66 (95% CI, 0.58-0.75). Our results confirmed the association of several nutritional factors intake and incident hypertension and highlighted that adopting a global healthy diet could strongly contribute to the prevention of hypertension.

Association between a dietary quality index based on the food standard agency nutrient profiling system and cardiovascular disease risk among French adults.

BACKGROUND: In France, the implementation of a front-of-pack (FOP) nutrition label-the 5-Colour Nutrition Label (5-CNL) is currently under consideration as a strategic tool to allow consumers making healthier food choices. This FOP label is based on the British Food Standards Agency Nutrient Profiling System (FSA-NPS), reflecting the overall nutritional quality of foods. At the individual level, an energy-weighted mean of all FSA-NPS scores of foods usually consumed has been elaborated (FSA-NPS DI). Our objective was to investigate the prospective association between the FSA-NPS DI and cardiovascular disease (CVD) risk. METHODS: 75,801 participants to the NutriNet-Santé cohort, who completed at least three 24h dietary records during the first 2y of the follow-up, were followed between 2009 and 2016. Multivariable Cox proportional hazards models were used to characterize the associations between FSA-NPS DI and the incidence of CVDs. RESULTS: 509 major cardiovascular events were diagnosed (262 coronary heart diseases and 247 strokes). A higher FSA-NPS DI, characterizing lower dietary quality, was associated with increased CVD risk (HRfor a 1-point increment=1.08 (1.03-1.13); HRQ4vs.Q1=1.40 (1.06-1.84), Ptrend Q4-Q1=0.01). This association tended to be stronger in overweight subjects (HRfor a 1-point increment=1.12 (1.04-1.19); Pinteraction=0.003). CONCLUSIONS: These results suggest that lower dietary quality, as reflected by a higher FSA-NPS DI, may be associated with a significant increase in cardiovascular risk, especially in at-risk individuals (overweight population). They support the public health relevance of developing a front-of-pack nutrition label based on this score.

Compliance with Nutritional and Lifestyle Recommendations in 13,000 Patients with a Cardiometabolic Disease from the Nutrinet-Santé Study.

BACKGROUND: A healthy diet has been shown to prevent cardiovascular diseases complications. The objective of this study was to assess dietary intakes and compliance with nutritional and lifestyle recommendations in French adults diagnosed with hypertension, diabetes, dyslipidaemia or cardiovascular disease compared with healthy individuals. METHODS: Data was collected from 26,570 subjects aged 35 to 70 years (13,285 patients and 13,285 controls matched by sex and age) of the French cohort NutriNet-Santé. Dietary intakes were assessed using three 24-h records. Mean food and nutrient intakes of patients were compared to those of healthy subjects using multivariable mixed logistic and linear regressions. RESULTS: Compared to healthy controls, adults reporting cardiometabolic diseases had lower intakes of sweetened products, higher intakes of fish and seafood and a better compliance with dairy products. However, overall, they reported unhealthier lifestyles and dietary habits. Indeed, they were less often physically active and had similar habits regarding alcohol and tobacco consumption. They also had lower intakes of fruit, higher intakes of meat, processed meat and added fats. It is noteworthy that diabetic subjects tended to show the highest compliance with certain dietary recommendations (vegetables, pulses and whole grain products). CONCLUSION: Our study brings into focus the fact that some nutritional aspects still need to be improved among individuals with a cardiometabolic disease. We should encourage higher intakes of fruits and vegetables, whole grain products, and lower intakes of meat and sodium, as well as healthy lifestyle (physical activity, no-smoking and limited intake of alcohol) in order to encourage a healthier management after being diagnosed.

Are self-reported unhealthy food choices associated with an increased risk of breast cancer? Prospective cohort study using the British Food Standards Agency nutrient profiling system.

OBJECTIVES: French authorities are considering the implementation of a simplified nutrition labelling system on food products to help consumers make healthier food choices. One of the most documented candidates (Five-Colour Nutrition Label/Nutri-score) is based on the British Food Standards Agency Nutrient Profiling System (FSA-NPS), a score calculated for each food/beverage using the 100 g amount of energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits and vegetables. To assess its potential public health relevance, studies were conducted on the association between the nutritional quality of the diet, measured at the individual level by an energy-weighted mean of all FSA-NPS scores of foods usually consumed (FSA-NPS dietary index (FSA-NPS DI)), and the risk of chronic diseases. The present study aimed at investigating the relationship between the FSA-NPS DI and breast cancer risk. DESIGN: Prospective study. SETTING: Population based, NutriNet-Santé cohort, France. PARTICIPANTS: 46 864 women aged ≥35 years who completed ≥3 24-hour dietary records during their first 2 year of follow-up. PRIMARY OUTCOME MEASURE: Associations between FSA-NPS DI and breast cancer risk (555 incident breast cancers diagnosed between 2009 and 2015) were characterised by multivariable-adjusted Cox proportional hazard models. RESULTS: A higher FSA-NPS DI (lower nutritional quality of the diet) was associated with an increased breast cancer risk (HR1-point increment=1.06 (1.02-1.11), p=0.005; HRQ5vs.Q1=1.52 (1.11-2.08), p trend=0.002). Similar trends were observed in premenopausal and postmenopausal women (HR1-point increment=1.09 (1.01-1.18) and 1.05 (1.00-1.11), respectively).This study was based on an observational cohort using self-reported dietary data, thus residual confounding cannot be entirely ruled out. Finally, this holistic approach does not allow investigating which factors in the diet most specifically influence breast cancer risk. CONCLUSIONS: These results suggested that unhealthy food choices, as characterised by the FSA-NPS, may be associated with an increase in breast cancer risk, supporting the potential public health relevance of using this profiling system in the framework of public health nutritional measures.

Prospective association between a dietary quality index based on a nutrient profiling system and cardiovascular disease risk.

BACKGROUND: Public health strategies are essential to guide consumers' choices and produce a substantial population impact on cardiovascular disease risk prevention through nutrition. Our aim was to investigate the prospective association between the Food Standards Agency nutrient profiling system dietary index (FSA-NPS DI) and cardiovascular disease risk. The FSA-NPS has been proposed to serve as a basis for a five-colour nutrition label suggested in France to be put on the front of pack of food products. METHODS AND RESULTS: A total of 6515 participants to the SU.VI.MAX cohort (1994-2007), who completed at least six 24-hour dietary records during the first two years of the study, were followed for a median of 12.4 years (25th-75th percentiles: 11.0-12.6). Multivariable Cox proportional hazards models were used to characterise the associations between FSA-NPS DI (continuous and sex-specific quartiles) and the incidence of cardiovascular diseases. Interactions with individual characteristics were tested; 181 major cardiovascular events were reported (59 myocardial infarctions, 43 strokes, 79 anginas). A higher FSA-NPS DI, characterising poorer food choices, was associated with an overall increase in cardiovascular disease risk (HRfor a 1-point increment = 1.14 (1.03-1.27); HRQ4vs.Q1 = 1.61 (1.05-2.47), Ptrend Q4-Q1 = 0.03). This association tended to be stronger in smokers (HRfor a 1-point increment = 1.39 (1.11-1.73); Pinteraction = 0.01) and those less physically active (HRfor a 1-point increment = 1.26 (1.08-1.46); Pinteraction = 0.04). CONCLUSIONS: Our results suggest that poorer food choices, as reflected by a higher FSA-NPS DI, may be associated with a significant increase in cardiovascular risk, especially in at-risk individuals (smokers and physically inactive persons). This score could be a useful tool for public health prevention strategies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00272428.