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Trillions of microorganisms inhabit the human gut and are regarded as potential key factors for health 1 , 2 . Characteristics such as diet, lifestyle, or genetics can shape the composition of the gut microbiota 2 – 6 and are usually shared by individuals from comparable ethnic origin. So far, most studies assessing how ethnicity relates to the intestinal microbiota compared small groups living at separate geographical locations 7 – 10 . Using fecal 16S ribosomal RNA gene sequencing in 2,084 participants of the Healthy Life in an Urban Setting (HELIUS) study 11 , 12 , we show that individuals living in the same city tend to share similar gut microbiota characteristics with others of their ethnic background. Ethnicity contributed to explain the interindividual dissimilarities in gut microbiota composition, with three main poles primarily characterized by operational taxonomic units (OTUs) classified as Prevotella (Moroccans, Turks, Ghanaians), Bacteroides (African Surinamese, South-Asian Surinamese), and Clostridiales (Dutch). The Dutch exhibited the greatest gut microbiota α-diversity and the South-Asian Surinamese the smallest, with corresponding enrichment or depletion in numerous OTUs. Ethnic differences in α-diversity and interindividual dissimilarities were independent of metabolic health and only partly explained by ethnic-related characteristics including sociodemographic, lifestyle, or diet factors. Hence, the ethnic origin of individuals may be an important factor to consider in microbiome research and its potential future applications in ethnic-diverse societies. Stool microbiota composition correlates with the ethnic backgrounds of people living in the same city, suggesting that geographical location and ethnicity have distinct effects on microbiota.

Abstract The gut microbiome is thought to play a role in depressive disorders, which makes it an attractive target for interventions. Both the microbiome and depressive symptom levels vary substantially across ethnic groups. Thus, any intervention for depression targeting the microbiome requires understanding of microbiome-depression associations across ethnicities. Analysing data from the HELIUS cohort, we characterize the gut microbiota and its associations with depressive symptoms in 6 ethnic groups (Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, Moroccan; N = 3211), living in the same urban area. Diversity of the gut microbiota, both within (α-diversity) and between individuals (β-diversity), predicts depressive symptom levels, taking into account demographic, behavioural, and medical differences. These associations do not differ between ethnic groups. Further, β-diversity explains 29%–18% of the ethnic differences in depressive symptoms. Bacterial genera associated with depressive symptoms belong to mulitple families, prominently including the families Christensenellaceae, Lachnospiraceae , and Ruminococcaceae . In summary, the results show that the gut microbiota are linked to depressive symptom levels and that this association generalizes across ethnic groups. Moreover, the results suggest that ethnic differences in the gut microbiota may partly explain parallel disparities in depression.

BACKGROUND:More than 330 food additives (e.g. artificial sweeteners, emulsifiers, dyes) are authorized in Europe, with a great variability of use across food products.OBJECTIVE:The objective of this study was to investigate the distribution and co-occurrence of food additives in a large-scale database of foods and beverages available on the French market.DESIGN:The open access crowdsourced Open Food Facts database (https://world.openfoodfacts.org/) was used to retrieve the composition of food and beverage products commonly marketed on the French market (n = 126,556), based on the ingredients list. Clustering of food additive variables was used in order to determine groups of additives frequently co-occurring in food products. The clusters were confirmed by network analysis, using the eLasso method.RESULTS:Fifty-three-point eight percent of food products contained at least 1 food additive and 11.3% at least 5. Food categories most likely to contain food additives (in more than 85% of food items) were artificially sweetened beverages, ice creams, industrial sandwiches, biscuits and cakes. The most frequently used food additives were citric acid, lecithins and modified starches (>10,000 products each). Some food additives with suspected health effects also pertained to the top 50: sodium nitrite, potassium nitrate, carrageenan, monosodium glutamate, sulfite ammonia caramel, acesulfame K, sucralose, (di/tri/poly) phosphates, mono- and diglycerides of fatty acids, potassium sorbate, cochineal, potassium metabisulphite, sodium alginate, and bixin (>800 food products each). We identified 6 clusters of food additives frequently co-occurring in food products.CONCLUSIONS:Food additives are widespread in industrial French products and some clusters of additives frequently co-occurring in food products were identified. These results pave the way to future etiological studies merging composition data to food consumption data to investigate their association with chronic disease risk, in particular potential 'cocktail effects'.

It is currently unknown whether associations between gut microbiota composition and type 2 diabetes (T2D) differ according to the ethnic background of individuals. Thus, we studied these associations in participants from two ethnicities characterized by a high T2D prevalence and living in the same geographical area, using the Healthy Life In Urban Settings (HELIUS) study. We included 111 and 128 T2D participants on metformin (Met-T2D), 78 and 49 treatment-naïve T2D (TN-T2D) participants, as well as a 1:1 matched group of healthy controls from, respectively, African Surinamese and South-Asian Surinamese descent. Fecal microbiome profiles were obtained through 16S rRNA gene sequencing. Univariate and machine learning analyses were used to explore the associations between T2D and the composition and function of the gut microbiome in both ethnicities, comparing Met-T2D and TN-T2D participants to their respective healthy control. We found a lower α-diversity for South-Asian Surinamese TN-T2D participants but no significant associations between TN-T2D status and the abundance of bacterial taxa or functional pathways. In African Surinamese participants, we did not find any association between TN-T2D status and the gut microbiome. With respect to Met-T2D participants, we identified several bacterial taxa and functional pathways with a significantly altered abundance in both ethnicities. More alterations were observed in South-Asian Surinamese. Some altered taxa and pathways observed in both ethnicities were previously related to metformin use. This included a strong negative association between the abundance of Romboutsia and Met-T2D status. Other bacterial taxa were consistent with previous observations in T2D, including reduced butyrate producers such as Anaerostipes hadrus. Hence, our results highlighted both shared and unique gut microbial biomarkers of Met-T2D in individuals from different ethnicities but living in the same geographical area. Future research using higher-resolution shotgun sequencing is needed to clarify the role of ethnicity in the association between T2D and gut microbiota composition.

AbstractObjectiveTo investigate the association between intake of food additive preservatives and cancer incidence in a large prospective cohort.DesignProspective cohort.SettingFrench NutriNet-Santé cohort, 2009-23.Participants105 260 participants (≥15 years) without prevalent cancer who completed at least two 24 hour dietary records at baseline.Main outcome measuresCumulative time dependent intake of preservatives, including those in industrial food brands, assessed using repeated 24 hour dietary records and evaluated through multiple composition databases and ad hoc laboratory assays in food products for the most frequently consumed additive-food pairs. Associations between intake of three categories of preservatives (defined as sex specific thirds if preservative was consumed by at least a third of participants, otherwise defined as non-consumers and lower or higher consumers separated by the sex specific median) and cancer incidence were characterised using multivariable proportional hazards Cox models adjusted for potential confounders.ResultsMean age of participants was 42.0 years (standard deviation (SD 14.5) years), and 78.7% were women. 4226 participants received a diagnosis of incident cancer (mean follow-up 7.57 (SD 4.56) years), comprising 1208 breast, 508 prostate, 352 colorectal, and 2158 other cancers). Higher intakes of several preservatives were associated with higher cancer incidence: total non-antioxidants with overall cancer (hazard ratio for higher v non-consumers or lower consumers 1.16 (95% confidence interval (CI) 1.07 to 1.26); absolute risk of cancer at age 60 years, respectively, 13.3%, 12.1%) and breast cancer (1.22 (1.05 to 1.41); 5.7%, 4.8%); total sorbates, specifically potassium sorbate, with overall cancer (1.14 (1.04 to 1.24); 13.4%, 11.8%) and breast cancer (1.26 (1.07 to 1.49); 5.7%, 4.6%); total sulfites with overall cancer (1.12 (1.02 to 1.24); 13.4%, 11.9%); potassium metabisulfite with overall cancer (1.11 (1.03 to 1.20); 13.5%, 12.0%) and breast cancer (1.20 (1.04 to 1.38); 5.7%, 4.9%); sodium nitrite with prostate cancer (1.32 (1.02 to 1.70); 4.2%, 3.4%); potassium nitrate with overall cancer (1.13 (1.05 to 1.23); 14.0%, 12.0%) and breast cancer (1.22 (1.05 to 1.41); 5.9%, 4.8%); total acetates with overall cancer (1.15 (1.06 to 1.25); 14.3%, 12.2%) and breast cancer (1.25 (1.07 to 1.45); 6.1%, 4.9%); acetic acid with overall cancer (1.12 (1.01 to 1.25); 14.4%, 12.4%); and sodium erythorbate with overall cancer (1.12 (1.04 to 1.22); 13.5%, 11.9%) and breast cancer (1.21 (1.04 to 1.41); 5.7%, 4.8%). 11 of the 17 individually studied preservatives were not associated with cancer incidence.ConclusionMultiple positive associations between intake of preservatives widely used in industrial foods and higher cancer incidence (overall, breast, and prostate) were observed in this large prospective cohort. Epidemiology based on health effect biomarkers and experimental research are needed to gain insight into outcome pathways. If confirmed, these new data call for the re-evaluation of regulations governing the food industry’s use of these additives, to improve consumer protection. In the meantime, the findings support recommendations for consumers to favour freshly made, minimally processed foods.Trial registrationClinicalTrials.gov NCT03335644.

This study aimed to identify exposures to food additives and their mixtures in a nationally representative sample of French adults and children. Using repeated 24-hour dietary recalls and food records (including commercial brand information) from the cross-sectional Esteban survey (France, 2016), additive intake was estimated by merging with multiple food composition databases, and laboratory assays in food matrices. Non-negative matrix factorisation was used to identify additive mixtures. Their associations with sociodemographic, lifestyle, and dietary factors were assessed using survey-weighted regressions. A total of 2,177 adults (18–74 years old) and 1,279 children (6–17 years old) were included. Mean daily additive intake was 4.42 g/day in adults and 5.08 g/day in children. Sixty additives were consumed by at least 5% of adults, and 71 by children, including several with suspected adverse health effects (e.g., carrageenan, acesulfame K, aspartame, titanium dioxide). Three main mixtures were identified in adults and four in children, and were correlated with distinct socio-demographic profiles. In conclusion, this first nationally representative assessment of food additive exposure in French children and adults provides the evidence that food additives are consumed as mixtures and, together with emerging data on synergistic interactions, it underscores the importance of considering combined exposures in future safety evaluations. Trial registration : The Esteban health survey is registered in the French National Agency for Medicines and Health Products Safety (No. 2012-A00456-34).

Abstract Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma. Candidate genes located within the two loci, CASZ1 and RXFP2 , are expressed in human and mouse adrenals in different cell clusters. Their overexpression in adrenocortical cells suppresses mineralocorticoid output under basal and stimulated conditions, without affecting cortisol biosynthesis. Our study identifies the first risk loci for primary aldosteronism and highlights new mechanisms for the development of aldosterone excess.

Mechanistic hypotheses suggest a potential effect of dietary fiber on breast carcinogenesis through the modulation of insulin-like growth factor bioactivity, estrogen metabolism and inflammation. An association between dietary fiber intake and breast cancer risk has been suggested in epidemiological studies but remains inconclusive. In particular, data is lacking regarding the different types of dietary fibers. The objective was to investigate the prospective relationship between dietary fiber intake and breast cancer risk, taking into account different types of dietary fiber (overall, insoluble, soluble and from different food sources: cereals, vegetables, fruits and legumes). 4684 women from the SU.VI.MAX cohort were included in this analysis as they completed at least three 24h-dietary records within the first two years of follow-up. Among them, 167 incident invasive breast cancers were diagnosed during a median follow-up of 12.6 years (between 1994 and 2007). The associations between quartiles of dietary fiber intake and breast cancer risk were characterized using multivariate Cox proportional hazards models. Total fiber intake was not associated with breast cancer risk (HR(Quartile4vs.Quartile1) = 1.29 (95%CI 0.66-2.50), P-trend = 0.5), nor was fiber intake from cereals (P-trend = 0.1), fruits (P-trend = 0.9) and legumes (P-trend = 0.3). In contrast, vegetable fiber intake was related to a decreased risk of breast cancer (HR(Q4vs.Q1) = 0.50 (0.29-0.88), P-trend = 0.03). Overall vegetable intake (in g/day) was not associated with breast cancer risk (P-trend = 0.2). This prospective study suggests that vegetable fiber intake may contribute to reduce breast cancer risk, in line with experimental mechanistic data.

Purpose Red and processed meats are recognized by the International Agency for Research on Cancer as probably carcinogenic and carcinogenic to humans, respectively. Heme iron has been proposed as a central factor responsible for this effect. Furthermore, anxiety affects the intestinal barrier function by increasing intestinal permeability. The objective of this work was to assess how anxiety modifies the association between red and processed meat consumption and cancer risk in the NutriNet-Santé prospective cohort (2009–2019). Methods Using multi-adjusted Cox models in a sample of 101,269 subjects, we studied the associations between the consumption of red and processed meat, the amount of heme iron coming from these meats and overall, colorectal, prostate, and breast cancer risks, overall and separately among participants with and without anxiety. Results An increase in red and processed meat consumption was associated with an increased risk of developing colorectal cancer in the total population (HR for an increase of 50 g/day = 1.18 (1.01–1.37), p  = 0.03). After stratification on anxiety, the HR 50 g/day was 1.42 (1.03–1.94, p  = 0.03) in anxious participants and 1.12 (0.94–1.33, p  = 0.20) in other participants. Similar trends were observed for overall cancer risk. Analyses conducted with heme iron also provided similar results. Conclusions Our results strengthen the existing body of evidence supporting that red and processed meat consumption and heme iron intake are associated with an increased risk of overall and more specifically colorectal cancer, and suggest that anxiety modifies these associations, with an increased risk in anxious participants.

BackgroundFood reformulation is promoted as a tool to improve the nutritional quality of population diets. However, the potential impact of industry-wide reformulation on dietary intake has been investigated minimally.ObjectivesThe aim was to estimate the impact on the French population nutrient intakes of industry-wide reformulation towards healthier products using the updated nutrient profiling system underpinning the front-of-pack nutrition label Nutri-Score (uNS-NPS).MethodsDietary data were retrieved from the Nutrinet-Santé cohort at baseline (N=100 418), providing detailed information regarding participants’ food choices (N>3000 generic food items). Each individual food from 24 hours dietary record was matched with French food market data from OpenFoodFacts database (N=119 073 products). Three scenarios were constructed using nutrient content of currently existing food products: (1) all products available (baseline situation); (2) only existing products of better nutritional quality were available as potential substitutes and (3) only existing products of poorer quality were available. The assessment of the nutritional quality was based on the uNS-NPS score. Finally, dietary intakes were calculated for each scenario after random attribution of healthier/less healthy products as dietary choices. Monte-Carlo iterations (n=300) were conducted to generate uncertainty intervals.ResultsAfter simulation of reformulation using scenario 2, reduction in daily intake in comparison with the baseline situation was observed for energy (–55 kcal/day, –2.9%), saturated fat (–2.4g/day, –7.6%), sugar (–4.8g/day, –5.3%) and salt (–0.54g/day, –8.3%) and increase was observed for fibre (+1.0g/day, +4.9%). Improvements in diet quality were observed regardless of the overall quality of diet. The most important contributors to diet improvement were the followings: (1) sugars: sugary products, sweet bakery products and dairy products; (2) saturated fat: sweet bakery products, dairy products and prepared dishes and (3) salt: bread, prepared dishes, vegetable preparations and soups.ConclusionWidespread reformulation of food offer appeared to be an opportunity for improving nutritional status at population level in France.