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.

Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort.

BACKGROUND: Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort. METHODS AND FINDINGS: This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design. CONCLUSIONS: In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.

Consistency of the Initial and Updated Version of the Nutri-Score with Food-Based Dietary Guidelines: A French Perspective.

BACKGROUND: To help consumers to make healthier food choices, 7 European countries have implemented the front-of-pack nutrition label Nutri-Score. The algorithm was updated in 2022-2023 by the Nutri-Score European scientific committee, based on the current scientific knowledge. OBJECTIVES: The aim of this study was to investigate the consistency of the newly internationally developed algorithm with the French food-based dietary guidelines (FBDG) and compare the respective performances of the initial and updated algorithm. METHODS: Three complementary French food composition databases were used to access extensive coverage of the food supply in France (n = 46,752): the Oqali, OpenFoodFacts, and CIQUAL databases. Based on the French FBDG, a list of 41 criteria was defined by which the consistency between French FBDG and the Nutri-Score was assessed (eg, consumption of fresh vegetables is promoted in FBDG, thus the Nutri-Score should rate favorably such products). RESULTS: Of all criteria, the initial algorithm met 63% (26/41) of them, whereas the revised algorithm met 85% (35/41) of them. Improvements achieved by the updated version of the Nutri-Score in alignment with the FBDG were particularly observed for high-fat products (ie, fatty fish, nuts, and seeds), sweet products (ie, ice creams and sweet spreads), salty products (ie, savory snacks and salted nuts), dairy beverages, and beverages with artificial sweeteners. CONCLUSIONS: The Nutri-Score's updated nutrient profiling system appears to rate foods more consistently regarding the French dietary guidelines and improved the currently existing system. This work supports the implementation of the updated nutrient profiling system underlying Nutri-Score.

A randomized controlled trial to test the effects of displaying the Nutri-Score in food advertising on consumer perceptions and intentions to purchase and consume.

BACKGROUND: Some research shows that advertising for high-fat, sugar, or salt (HFSS) products is contributing to a shift in consumer preferences toward products of poor nutritional quality, leading to unhealthy nutritional intakes that increase the risk of obesity and chronic diseases. A strategy of displaying simple and understandable nutritional information (like the front-of-pack nutrition label Nutri-Score) in food messages could be an aid to help guide consumers' choice towards healthier products. METHODS: A randomized controlled experiment was conducted on 27,085 participants randomly assigned to two experimental conditions or a control condition. In both experimental conditions (independent variable: advertising messages with vs. without the Nutri-Score), participants were exposed to advertisements for diversified food products with contrasting nutritional quality and belonging to nine different food categories. Participants were then asked questions about their perception, affective evaluation, and intentions to purchase and consume the products. In the control condition, they were not exposed to the advertisements. RESULTS: Overall, interaction effects between the two variables (1) the messages with vs. without the Nutri-Score and (2) the nutritional quality of products, were significant for all dependent variables, with effect sizes between large and medium. Overall, the better the products' nutritional quality, the more positive their perceptions, affective evaluations, and intentions to buy and consume them. When the Nutri-score was displayed in advertising messages (vs. when it was not), perceptions, affective evaluation, and behavioral intentions: (1) became more positive for products of good nutritional quality (Nutri-score A and B), (2) became more negative for products of poor nutritional quality (Nutri-score D and E), (3) changed little or not at all for products of intermediate nutritional quality (Nutri-Score C). CONCLUSIONS: This research is the first in the literature to demonstrate that displaying the Nutri-Score in advertising messages assists consumers in directing their choices towards healthier foods. Regulations mandating the display of the Nutri-Score in food advertising could be an effective public health measure.

Complementarity between the updated version of the front-of-pack nutrition label Nutri-Score and the food-processing NOVA classification.

OBJECTIVE: To compare the initial and the updated versions of the front-of-pack label Nutri-Score (related to the nutritional content) with the NOVA classification (related to the degree of food processing) at the food level. DESIGN: Using the OpenFoodFacts database - 129,950 food products - we assessed the complementarity between the Nutri-Score (initial and updated) with the NOVA classification through a correspondence analysis. Contingency tables between the two classification systems were used. SETTINGS: The food offer in France. PARTICIPANTS: Not applicable. RESULTS: With both versions (i.e. initial and updated) of the Nutri-Score, the majority of ultra-processed products received medium to poor Nutri-Score ratings (between 77·9 % and 87·5 % of ultra-processed products depending on the version of the algorithm). Overall, the update of the Nutri-Score algorithm led to a reduction in the number of products rated A and B and an increase in the number of products rated D or E for all NOVA categories, with unprocessed foods being the least impacted (-3·8 percentage points (-5·2 %) rated A or B and +1·3 percentage points (+12·9 %) rated D or E) and ultra-processed foods the most impacted (-9·8 percentage points (-43·4 %) rated A or B and +7·8 percentage points (+14·1 %) rated D or E). Among ultra-processed foods rated favourably with the initial Nutri-Score, artificially sweetened beverages, sweetened plant-based drinks and bread products were the most penalised categories by the revision of Nutri-Score while low-sugar flavoured waters, fruit and legume preparations were the least affected. CONCLUSION: These results indicate that the update of the Nutri-Score reinforces its coherence with the NOVA classification, even though both systems measure two distinct health dimensions at the food level.

The association between consideration of future consequences and food intake is mediated by food choice motives in a French adult population.

OBJECTIVES: Consideration of future consequences (CFC) distinguishes individuals who adopt behaviours based on immediate needs and concerns from individuals who consider the future consequences of their behaviours. We aimed to assess the association between CFC and diet, and testing the mediating role of food choice motives on this relationship. DESIGN: Individuals (aged ≥ 18 years) completed the CFC-12 questionnaire in 2014, at least three 24-h dietary records, and a food choice motive questionnaire. A multiple mediator analysis allowed to assess the mediating effect of food choice motives on the cross-sectional association between CFC and diet, adjusted for socio-demographic factors. SETTING: Data from the NutriNet-Santé cohort study. PARTICIPANTS: 27 330 participants. RESULTS: CFC was associated with all food choice motives (P < 0·001), with the strongest positive associations for avoidance for environmental reasons, absence of contaminants and health motives and the strongest negative associations for innovation and convenience. Positive total effects were found between CFC and the consumption of healthy food groups (fruits and vegetables, whole-grain foods, legumes), and negative total effects for alcohol, meat and poultry and processed meat (P < 0·001). CFC was positively associated with diet quality (P < 0·001). Across food groups, major mediators of these relationships were higher health (8·4-32·6%), higher environmental (13·7-22·1 %) and lower innovation (7·3-25·1 %) concerns. CONCLUSIONS: CFC was associated with healthier dietary intake, essentially mediated by a greater motivation of future-oriented participants for self-centred and altruistic outcomes, including health and environment. Focusing on the awareness of future benefits in public health interventions might lead to healthier dietary behaviours.

Cross-sectional and longitudinal associations between self-esteem and BMI depends on baseline BMI category in a population-based study.

BACKGROUND: Some studies have reported associations between self-esteem and weight status, but longitudinal data on adults remain scarce. The aim of this population-based study was to analyze the cross-sectional and longitudinal association between self-esteem and body mass index (BMI) and to investigate whether baseline BMI has an impact on this association. METHODS: In 2016, 29,735 participants aged ≥ 18 years in the NutriNet-Santé cohort completed the Rosenberg Self-Esteem Scale. BMI was self-reported yearly over a 4-year period. Association between self-esteem and BMI was assessed using mixed models and logistic regressions. Analyses were stratified by BMI (categorical) at baseline and adjusted on sociodemographic and lifestyle characteristics. RESULTS: At baseline, higher self-esteem was associated with higher BMI in normal weight individuals(p = 0.32), and with lower BMI in obese class II and III individuals (p = 0.13). In addition, higher baseline self-esteem was associated with BMI increase over time in normal weight individuals (p = 0.15). Among normal weight individuals, those with higher self-esteem were less likely to show a decrease in their BMI (p = 0.005), while no association was observed with BMI increase (p = 0.81). DISCUSSION: Our findings suggest that the association between self-esteem and BMI depends on the initial category of BMI, with a negligible effect of self-esteem.

Dietary exposure to nitrites and nitrates in association with type 2 diabetes risk: Results from the NutriNet-Santé population-based cohort study.

BACKGROUND: Nitrites and nitrates occur naturally in water and soil and are commonly ingested from drinking water and dietary sources. They are also used as food additives, mainly in processed meats, to increase shelf life and to avoid bacterial growth. Experimental studies suggested both benefits and harmful effects of nitrites and nitrates exposure on type 2 diabetes (T2D) onset, but epidemiological and clinical data are lacking. We aimed to study these associations in a large population-based prospective cohort study, distinguishing foods and water-originated nitrites/nitrates from those from food additives. METHODS AND FINDINGS: Overall, 104,168 adults from the French NutriNet-Santé cohort study (2009 to 2021, 79.1% female, mean age [SD] = 42.7 [14.5]) were included. Associations between self-reported exposure to nitrites and nitrates (evaluated using repeated 24-h dietary records, linked to a comprehensive food composition database and accounting for commercial names/brands details of industrial products) and risk of T2D were assessed using cause-specific multivariable Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). During a median follow-up duration of 7.3 years (interquartile range: [3.2; 10.1] years), 969 incident T2D cases were ascertained. Total nitrites and foods and water-originated nitrites were both positively associated with a higher T2D risk (HRtertile 3 vs.1 = 1.27 (95% CI 1.04 to 1.54), Ptrend = 0.009 and 1.26 (95% CI 1.03 to 1.54), Ptrend = 0.02, respectively). Participants with higher exposure to additives-originated nitrites (i.e., above the sex-specific median) and specifically those having higher exposure to sodium nitrite (e250) had a higher T2D risk compared with those who were not exposed to additives-originated nitrites (HR higher consumers vs. non-consumers = 1.53 (95% CI 1.24 to 1.88), Ptrend < 0.001 and 1.54 (95% CI 1.26 to 1.90), Ptrend < 0.001, respectively). There was no evidence for an association between total, foods and water-originated, or additives-originated nitrates and T2D risk (all Ptrend = 0.7). No causal link can be established from this observational study. Main limitations include possible exposure measurement errors and the lack of validation versus specific nitrites/nitrates biomarkers; potential selection bias linked to the healthier behaviors of the cohort's participants compared to the general population; potential residual confounding linked to the observational design, as well as a self-reported, yet cross-checked, case ascertainment. CONCLUSIONS: The findings of this large prospective cohort did not support any potential benefits for dietary nitrites and nitrates. They suggested that a higher exposure to both foods and water-originated and additives-originated nitrites was associated with higher T2D risk in the NutriNet-Santé cohort. This study provides a new piece of evidence in the context of current debates about updating regulations to limit the use of nitrites as food additives. The results need to be replicated in other populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644 (https://clinicaltrials.gov/ct2/show/NCT03335644).

Stages of Change toward Meat Reduction: Associations with Motives and Longitudinal Dietary Data on Animal-Based and Plant-Based Food Intakes in French Adults.

BACKGROUND: Reducing meat consumption is advocated for healthier and more sustainable diets. However, behavioral studies are needed to better understand the mechanisms underlying meat-reducing dietary changes. OBJECTIVES: The main aim of this study was to compare the motives associated with stages of change toward meat reduction in French adults, using the transtheoretical model (TTM). A second aim was to investigate the associations between stages of change and adherence to dietary patterns favoring a better balance of animal and plant food consumption over time. METHODS: This longitudinal study included 25,143 non-vegetarian participants of the web-based NutriNet-Santé cohort with a mean follow-up of 6.2 (SD = 2.6) y. Dietary data were obtained from 24-h dietary records over the period 2009-2019. The contribution of meat to total energy intake and scores measuring the contribution of healthy and unhealthy plant-based foods to the diet were computed. A questionnaire completed in 2018 allowed us to identify the TTM stages of change related to meat reduction (precontemplation, contemplation, preparation, action, and maintenance), and recorded motives related to meat consumption. We used multivariate linear mixed models for repeated data to assess associations between food intake changes and stages, and logistic regression for motives, presented as adjusted frequencies. RESULTS: Participants in later stages were characterized by a significantly higher decrease in meat intake over time, compared with the earliest stage (for example, ßmaintenance ∗ time = -0.08, P < 0.0001), and a higher increase in the healthy plant-based food consumption score over time (for example, ßmaintenance∗time = 0.11, P < 0.0001). Concerns about health, nutrition, and the environment were the most frequently cited motives for reducing meat consumption at all stages. CONCLUSIONS: Individuals who had already initiated meat reduction adhered to healthier and more sustainable diets than meat continuers. Characterizing motives according to readiness to reduce meat consumption could support tailored public health campaigns. TRIAL REGISTRATION NUMBER: The study protocol is registered at clinicaltrials.gov with Clinical Trial Registry number NCT03335644 available at https://clinicaltrials.gov/ct2/show/NCT03335644.

Sustainability analysis of the Mediterranean diet: results from the French NutriNet-Santé study.

The Mediterranean diet is often proposed as a sustainable diet model. This study aimed to evaluate the associations between adherence to the Mediterranean diet and sustainability domains in a cohort of French adults, using multiple criteria including nutritional quality, environmental pressures, monetary cost and dietary pesticide exposure. Food intakes of 29 210 NutriNet-Santé volunteers were assessed in 2014 using a semi-quantitative FFQ. Adherence to the Mediterranean diet was evaluated using the validated literature-based adherence score (MEDI-LITE). The associations between the MEDI-LITE and various sustainability indicators were examined using ANCOVA models, adjusted for sex, age and energy intake. Higher adherence to the MEDI-LITE was associated with higher nutritional quality scores, better overall nutrient profile as well as reduced environmental impact (land occupation: Q5 v. Q1: -35 %, greenhouse gas emissions: -40 % and cumulative energy demand: -17 %). In turn, monetary cost increased with increasing adherence to the Mediterranean diet (Q5 v. Q1: +15 %), while higher adherents to the Mediterranean diet had overall higher pesticide exposure due to their high plant-based food consumption. In this large cohort of French adults, greater adherence to the Mediterranean diet was associated with nutritional and environmental benefits, but also with higher monetary cost and greater exposure to pesticides, illustrating the necessity to develop large-scale strategies for healthy, safe (pesticide- and contaminant-free) and environmentally sustainable diets for all.

Respective contribution of ultra-processing and nutritional quality of foods to the overall diet quality: results from the NutriNet-Santé study.

BACKGROUND: Both the nutritional quality of the foods consumed (as nutrient composition) and their ultra-processed nature have been linked to health risks. However, the respective contribution of each of these correlated dimensions or their synergy to the overall diet quality has been rarely explored. OBJECTIVE: To identify the respective effects of the nutritional quality of the foods consumed, the ultra-processed nature of foods and their cross-effect contributing to the overall quality of the diet. DESIGN: Cross-sectional observational study. SETTING: Web-based French NutriNet-Santé cohort study. PARTICIPANTS: Participants in the NutriNet-Santé cohort study with at least three available 24 h records as baseline dietary data (N = 98 454 participants). MAIN OUTCOME MEASURES: The overall quality of the diet (qualified using the adherence to the 2017 French national nutrition and health dietary recommendations dietary score PNNS-GS2) was broken down into: (1) an effect of the nutritional quality of the foods consumed (qualified using the modified Foods Standards Agency nutrient profile model (underlying the Nutri-Score) dietary index FSAm-NPS DI); (2) an effect of the ultra-processed nature of the foods consumed (qualified using the proportion of ultra-processed foods consumed UPFp using the NOVA classification), and (3) a cross-effect of both dimensions. RESULTS: The overall effect from the 'nutritional quality of the foods consumed' (FSAm-NPS DI) was 1.10, corresponding to 26% of the total effect; the overall effect from ultra-processed foods consumption was 1.29, corresponding to 30% of the total effect; and cross-effect between nutritional quality of the foods consumed and ultra-processing was at 1.91, corresponding to 44% of total effects. CONCLUSIONS: Our study provides support to the postulate that nutritional quality and ultra-processing should be considered as two correlated but distinct and complementary dimensions of the diet.

Cross-sectional comparisons of dietary indexes underlying nutrition labels: nutri-score, Canadian 'high in' labels and Diabetes Canada Clinical Practices (DCCP).

PURPOSE: To assess the cross-sectional association between dietary indexes (DI) that underlie, respectively, the Nutri-score (NS), the proposed Canadian 'High In' Symbol (CHIL) and the Diabetes Canada Clinical Practice Guidelines (DCCP) with food consumption, nutrient intakes and metabolic markers. METHODS: 1836 adults (18-74 years) participating in the representative ESTEBAN study, conducted in mainland France in 2014-2016, were included in the analysis. Food consumption was assessed with three repeated 24 h dietary recalls. Anthropometric measurements and biomarkers of metabolic risk (cholesterol-total, LDL (Low Density Lipoprotein), HDL (High Density Lipoprotein)-triglycerides, glucose) were obtained through a clinical examination and fasting blood draw. The DI were assessed for their association with food consumption, dietary intakes and metabolic biomarkers as quintiles and continuous variables using multi-adjusted linear regression. Heathier diets were assigned to lower scores. RESULTS: Correlations between scores ranged from + 0.62 between CHIL-DI and NS-DI to + 0.75 between NS-DI and DCCP-DI. All DIs discriminated individuals according to the nutritional quality of their diets through food consumption and nutrient intakes (healthier diets were associated with lower intakes of energy, added sugars and saturated fat; and with higher intakes of fiber, vitamins and minerals). NS-DI was associated with blood glucose (adjusted mean in Q1 = 5 vs. Q5 = 5.46 mmol/dl, ptrend = 0.001) and DCCP-DI was associated with BMI (Q1 = 24.8 kg/m2 vs. Q5 = 25.8 kg/m2, ptrend = 0.025), while CHIL showed no significant association with any anthropometric measures or biomarkers. CONCLUSIONS: This study provides elements supporting the validity of the nutrient profiling systems underlying front-of-package nutrition labellings (FOPLs) to characterize the healthiness of diets.

Periodontitis assessed with a new screening tool and oral health-related quality of life: cross-sectional findings among general-population adults.

INTRODUCTION: Periodontitis, as a chronic, multifactorial inflammatory disease, has complex relationships with other diseases and ultimately with well-being. The aim of this cross-sectional study was to investigate the association between self-report periodontitis, as measured with the recently developed and validated modified Periodontal Screening Score (mPESS), and oral health-related quality of life (OHRQol) in a large population-based sample derived from the French NutriNet-Santé e-cohort. METHODS: The sample was composed of 32,714 adults (75.5% women) with a mean age of 48.8 ± 13.9 years. Periodontitis was assessed based on age, smoking, and oral health status data obtained in 2011-2012, which allowed calculating the mPESS. An mPESS ≥ 5 was used to identify individuals at risk of severe periodontitis (main exposure). OHRQoL was measured with the Oral Health Impact Profile (OHIP-14) (main outcome) and the total score was dichotomized for analysis. Multivariable logistic regression analyses, considering physical health status, dietary and lifestyle confounding variables, were performed. RESULTS: Overall, 6407 participants (19.6%) were at a high risk of severe periodontitis. A total of 7383 participants (22.6%) presented a relatively poor OHRQoL (OHIP-14 > 8, highest quartile). In the multivariable model, each of the following variables was independently and significantly associated with lower OHRQoL: older age (50-64 years), female sex, obesity, snacking between meals, frequent consumption of soft drinks and sweets/chocolate, risk of severe periodontitis, and having < 20 natural teeth were significantly. An mPESS ≥ 5 showed the highest odds for relatively poor OHRQoL (OR = 3.45; 95% CI 3.21-3.72). CONCLUSION: The results support the association between periodontitis and OHRQoL in non-clinical samples. The use of mPESS could be tested in future prevention programs aiming at improving OHRQoL.

Behavioural risk patterns in adolescents with excess weight participating in the PRALIMAP-INÈS trial.

OBJECTIVE: To investigate clustering of risk behaviours in adolescents with excess weight. DESIGN: Cross-sectional analysis of baseline data from the PRALIMAP-INÈS trial. Information on food frequency consumption (fruit, vegetables, sugary products and beverages), physical activity, sedentary behaviour (week and weekend days), smoking and alcohol consumption (current frequency and intoxication episodes) and socio-demographic data was collected using self-reported questionnaires. Behavioural risk factors were entered as categorical variables in a two-step clustering procedure: multiple correspondence analysis followed by hierarchical clustering. Associations between cluster membership and socio-demographic variables were investigated using multivariable multinomial logistic regression. SETTING: French PRALIMAP-INÈS trial. PARTICIPANTS: Adolescents with excess weight. RESULTS: A total of 1391 participants (13-18 years old, 58·2 % female) were included in the analysis, which resulted in the identification of four groups of participants, including, respectively, 543 (39·0 %), 373 (26·8 %), 246 (17·7 %) and 229 (16·5 %) participants. Clusters 1 and 4 showed associations of rather healthy behaviours (high physical activity and low consumption of sugary products; high consumption of fruit and vegetables, respectively), while clusters 2 and 3 showed associations of rather unhealthy behaviours (high sedentary behaviour and low consumption of fruit and vegetables; smoking and alcohol consumption, respectively). Both social status and family structure were associated with cluster membership. CONCLUSIONS: Risk behaviour patterns in adolescents with excess weight were clustered in both healthier and less healthy ways, with a complex interplay with socio-demographic factors.

Associations between measures of socio-economic position and sustainable dietary patterns in the NutriNet-Santé study.

OBJECTIVE: We aimed to explore the relationship between socio-economic characteristics and sustainable dietary patterns. DESIGN: Dietary data were derived from a web-based FFQ. Diet sustainability was evaluated using a modified Sustainable Diet Index, comprising nutritional, environmental and cultural components (higher scores expressing higher sustainability). The socio-economic position markers were education, household income and occupation status. Multi-adjusted linear and Poisson regression models were used to assess the cross-sectional association of the markers of socio-economic status with a sustainable diet and sustainability subcomponents, respectively. SETTING: France. PARTICIPANTS: 29 119 NutriNet-Santé participants. RESULTS: Individuals with a more sustainable diet had slightly higher diet monetary cost, lower total energy intake and consumed less animal-based foods than their counterparts. Lower education level was associated with lower overall diet sustainability (ßprimary v. postgraduate = -0·62, 95 % CI (-0·72, -0·51)) and nutrition, socio-cultural and environmental subscores. Manual workers and employees had a lower modified Sustainable Diet Index than intermediate professionals (ßmanual workers v. intermediate professionals = -0·43, 95 % CI (-0·52, -0·33) and ßemployees v. intermediate professionals = -0·56, 95 % CI (-0·64, -0·48)). Participants with the lowest v. highest incomes had a higher environmental subscore but a lower socio-cultural subscore, whereas the results were less marked for occupational status. CONCLUSIONS: Overall, our results documented associations between socio-economic status and the level of diet sustainability, arguing for the implementation of appropriate food policies to promote sustainable diets at lower cost.

Exposome Profiles and Asthma among French Adults.

Rationale: Although previous studies in environmental epidemiology focused on single or a few exposures, a holistic approach combining multiple preventable risk factors is needed to tackle the etiology of multifactorial diseases such as asthma. Objectives: To investigate the association between combined socioeconomic, external environment, early-life environment, and lifestyle-anthropometric factors and asthma phenotypes. Methods: A total of 20,833 adults from the French NutriNet-Santé cohort were included (mean age, 56.2 yr; SD, 13.2; 72% women). The validated asthma symptom score (continuous) and asthma control (never asthma, controlled asthma, and uncontrolled asthma) were considered. The exposome (n = 87 factors) covered four domains: socioeconomic, external environment, early-life environment, and lifestyle-anthropometric. Cluster-based analyses were performed within each exposome domain, and the identified profiles were studied in association to asthma outcomes in negative binomial (asthma symptom score) or multinomial logistic (asthma control) regression models. Measurements and Main Results: In total, 5,546 (27%) individuals had an asthma symptom score ⩾1, and 1,206 (6%) and 194 (1%) had controlled and uncontrolled asthma, respectively. Three early-life exposure profiles ("high passive smoking-own dogs," "poor birth parameters-daycare attendance-city center," or "⩾2 siblings-breastfed" compared with "farm-pet owner-molds-low passive smoking") and one lifestyle-anthropometric profile ("unhealthy diet-high smoking-overweight" compared with "healthy diet-nonsmoker-thin") were associated with more asthma symptoms and uncontrolled asthma. Conclusions: This large-scale exposome-based study revealed early-life and lifestyle exposure profiles that were at risk for asthma in adults. Our findings support the importance of multiinterventional programs for the primary and secondary prevention of asthma, including control of specific early-life risk factors and promotion of a healthy lifestyle in adulthood.

Comparative understanding and preference of Nutri-Score and NutrInform Battery in a sample of Spanish consumers.

BACKGROUND: Interpretive front-of-pack labels (FoPLs) are supported by World Health Organization as an important policy tool to promote healthy diets. At present, various FoPLs formats co-exist in the European Union (EU). However, as part of the Farm to Fork strategy published in 2020, the European Commission stated that it would propose a single mandatory FoPL. The aim of this study was to analyze Spanish consumers' preference and objective understanding of Nutri-Score and NutrInform, two FoPLs that are currently the subject of debate in the EU. METHODS: In a representative sample of 1026 Spanish adults (50% women, mean age ± SD = 46 ± 14 years), objective understanding was assessed by asking participants to identify the healthiest food products in three food categories (breakfast products, breakfast cereals and added fats). The preference dimensions were tested by asking participants about the perceived helpfulness of the FoPL in discriminating the nutritional quality of food products (subjective understanding) and their overall assessment of the FoPL's ease of use, informativeness, trust and liking (perception). RESULTS: In terms of objective understanding, Nutri-Score was significantly associated with an increase in consumers' ability to identify healthier food products across all food categories compared with NutrInform [OR (odds ratio) = 19.1 [14.2-25.7], P < 0.0001]. On the preference dimension, Nutri-Score was perceived as significantly easier to use and was more liked than NutrInform (standardized principal component analysis dimension, respectively, 0.32 ± 1.58 vs. -0.29 ± 1.66, P < 0.0001 and 0.080 ± 1.18 vs. -0.072 ± 1.17, P = 0.039). CONCLUSIONS: This study provides new evidence to support Nutri-Score in comparison with NutrInform in Spanish consumers, on both objective understanding and preference aspects.

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.

Dairy product consumption and risk of cancer: A short report from the NutriNet-Santé prospective cohort study.

The impact of dairy product consumption for long-term health remains unclear, in particular regarding their involvement in cancer etiology for frequent locations like breast or prostate. Besides, little is known about potentially different effects of dairy product subtypes. Our objective was therefore to evaluate the associations between dairy product consumption (total and subtypes) and cancer risk. A total of 101 279 participants from the French NutriNet-Santé cohort study were included (78.7% women; mean [SD] age = 42.2 [14.5] years). Dairy product consumption was assessed using validated web-based 24-hour dietary records. Multiadjusted Cox models were computed. After a median [interquartile range] follow-up time of 5.9 [2.7-8.3] years, we documented 2503 incident cancer cases (783 breast, 323 prostate and 182 colorectal cancers). Total dairy product consumption was not significantly associated with cancer. However, the consumption of "fromage blanc" (a French type of quark/cottage cheese) was associated with an increased risk of cancer overall (HR for 1 serving increment [95% CI] = 1.11 [1.01-1.21]; P-trend = .03) and of colorectal cancer (HR = 1.39 [1.09-1.77]; P-trend < .01). Besides, sugary dairy dessert consumption was directly associated with colorectal cancer risk (HR for 1 serving increment = 1.58 [1.01-2.46]; P-trend = .046]. No association was observed between the consumption of dairy products or sugary dairy desserts and the risk of prostate and breast cancers. In our study, the consumption of dairy products was not associated with the risk of overall, colorectal, breast or prostate cancers. The consumption of "fromage blanc" and sugary dairy desserts were associated to an increased risk of colorectal cancer, but this warrants further investigations.

Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study.

BACKGROUND: The food industry uses artificial sweeteners in a wide range of foods and beverages as alternatives to added sugars, for which deleterious effects on several chronic diseases are now well established. The safety of these food additives is debated, with conflicting findings regarding their role in the aetiology of various diseases. In particular, their carcinogenicity has been suggested by several experimental studies, but robust epidemiological evidence is lacking. Thus, our objective was to investigate the associations between artificial sweetener intakes (total from all dietary sources, and most frequently consumed ones: aspartame [E951], acesulfame-K [E950], and sucralose [E955]) and cancer risk (overall and by site). METHODS AND FINDINGS: Overall, 102,865 adults from the French population-based cohort NutriNet-Santé (2009-2021) were included (median follow-up time = 7.8 years). Dietary intakes and consumption of sweeteners were obtained by repeated 24-hour dietary records including brand names of industrial products. Associations between sweeteners and cancer incidence were assessed by Cox proportional hazards models, adjusted for age, sex, education, physical activity, smoking, body mass index, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, and baseline intakes of energy, alcohol, sodium, saturated fatty acids, fibre, sugar, fruit and vegetables, whole-grain foods, and dairy products. Compared to non-consumers, higher consumers of total artificial sweeteners (i.e., above the median exposure in consumers) had higher risk of overall cancer (n = 3,358 cases, hazard ratio [HR] = 1.13 [95% CI 1.03 to 1.25], P-trend = 0.002). In particular, aspartame (HR = 1.15 [95% CI 1.03 to 1.28], P = 0.002) and acesulfame-K (HR = 1.13 [95% CI 1.01 to 1.26], P = 0.007) were associated with increased cancer risk. Higher risks were also observed for breast cancer (n = 979 cases, HR = 1.22 [95% CI 1.01 to 1.48], P = 0.036, for aspartame) and obesity-related cancers (n = 2,023 cases, HR = 1.13 [95% CI 1.00 to 1.28], P = 0.036, for total artificial sweeteners, and HR = 1.15 [95% CI 1.01 to 1.32], P = 0.026, for aspartame). Limitations of this study include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns. CONCLUSIONS: In this large cohort study, artificial sweeteners (especially aspartame and acesulfame-K), which are used in many food and beverage brands worldwide, were associated with increased cancer risk. These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.