Associations between untargeted plasma metabolomic signatures and gut microbiota composition in the Milieu Intérieur population of healthy adults.

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

Sex-specific associations of different anthropometric indices with acute and chronic insomnia.

Background: Sleep disorders, including insomnia, are risk factors for weight gain. However, few epidemiological studies have investigated the association of anthropometric markers with insomnia as an outcome. Methods: In this observational, cross-sectional study, we assessed the association of 3 different anthropometric indices with acute and chronic insomnia. We used data from 13 389 French adults (mean age= 51.9 ± 13.1 years; 70.3% women) enrolled in the NutriNet-Santé-Biobank cohort. Body weight, height, waist and hip circumference were measured once during a clinic visit (2011-14). Body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were the main predictors. Acute (past 8 days) and chronic (≥3 months) insomnia were assessed in 2014 via a self-report questionnaire. We fit multivariable logistic regression models providing odds ratios (OR) and 95% confidence intervals (CI). Results: Overweight (25.0 ≤ BMI < 30.0 kg/m2) and general obesity (BMI ≥ 30.0 kg/m2) appeared to have an inverse association with acute insomnia only among men (overweight: OR= 0.80, 95% CI: 0.70, 0.92; obesity: OR= 0.78, 95% CI: 0.63, 0.98). Obesity assessed by BMI and WHR appeared to be positively associated with chronic insomnia only among women (BMI: OR= 1.23, 95% CI: 1.04, 1.45; WHR: OR= 2.24, 95% CI: 1.07, 4.72). WC did not display any significant associations in either sex. Conclusions: These cross-sectional results revealed sex-specific associations of overweight/obesity with different types of insomnia, and merit confirmation longitudinally with objectively assessed sleep parameters. Nonetheless, the findings reinforce the critical importance of joint health behaviour promotion.

Major Change in Body Weight over 5 Years and Total Sleep Time: Investigation of Effect Modification by Sex and Obesity in a Large e-Cohort.

PURPOSE: We assessed the association of long-term weight change ≥5 kg with total sleep time (TST), investigating effect modification by sex and overweight/obesity. METHOD: In a cross-sectional context, we studied 41,610 adults from the general population-based NutriNet-Santé e-cohort. A sleep questionnaire was self-administered in 2014. It included sleep logs for the estimation of average TST at night, and items for the calculation of major weight change as experienced over the previous 5 years. We fit multivariate polytomous logistic regression models. RESULTS: Overall, women with major weight loss had an increased likelihood of short TST (≤6 h) when compared with women with stable weight (OR = 1.15, 95% CI: 1.05-1.25). Individuals with major weight gain had an increased likelihood of short TST compared with their counterparts with stable weight (men: OR = 1.20, 95% CI: 1.05-1.37; women: OR = 1.24, 95% CI: 1.15-1.33). Men with major weight gain were less likely to report long TST compared with men with stable weight (OR = 0.83, 95% CI: 0.70-0.97). Overweight or obesity did not moderate the associations. CONCLUSIONS: The study advances knowledge in the fields of public health and nutrition by providing some evidence of a sex-specific association of major weight change with both short and long TST. These associations merit future investigation in a longitudinal context with repeated, objective measures of both weight and sleep time, while applying more stringent interaction test criteria and accounting for changes in health behaviors.

Impact of the First COVID-19 Pandemic Wave on Hospitalizations and Deaths Caused by Geriatric Syndromes in France: A Nationwide Study.

BACKGROUND: The fear of contracting coronavirus disease 2019 (COVID-19) and the preventive measures taken during the health crisis affected both people's lifestyles and the health system. This nationwide study aimed to investigate the impact of the first wave of the COVID-19 pandemic on hospitalizations and mortality related to geriatric syndromes (GS) in older adults in France. METHODS: The French National Health Data System was used to compare hospital admissions (excluding the main diagnosis of COVID-19) and mortality rates (using multiple-cause and initial-cause analyses, and both including or excluding confirmed/probable COVID-19) related to 10 different GS (dementia, other cognitive disorders and symptoms, delirium/disorientation, depression, undernutrition/malnutrition, dehydration, pressure ulcer, incontinence, fall/injury and femoral neck fracture) from January to September 2020 to rates observed in previous years. Analyses were stratified by age, sex, place of residence or place of death, and region. RESULTS: Hospitalization rates for all GS decreased during the first lockdown compared to the same periods in 2017-19 (from -59% for incontinence to -13% for femoral neck fractures). A dose-response relationship was observed between reduced hospitalizations and COVID-19-related mortality rates. Conversely, for almost all GS studied, excess mortality without COVID-19 was observed during this lockdown compared to 2015-17 (from +74% for delirium/disorientation to +8% for fall/injury), especially in nursing homes and at home. CONCLUSIONS: In France, during the first lockdown, a substantial decrease in hospitalizations for GS was accompanied by excess mortality. This decline in the use of services, which persisted beyond lockdown, may have a mid- and long-term impact on older adults' health.

Identifying profiles of people aged 65 and over who fall at home and associated falling-induced injuries: The French ChuPADom study.

BACKGROUND: Falls in older people are a major public health problem due to associated morbidity and mortality. Their origin is most often multifactorial. OBJECTIVE, DESIGN AND SUBJECTS: The objective of the present study, called ChuPaDom, was to identify patterns or profiles of home fallers (HF) - understood here as people who fall in their place of residence - among a sample of persons aged 65 and over who were hospitalized after a fall, and to study their association with falling-induced injuries using data from the ChuPAdom study. METHODS: Multiple correspondence analysis and Hierarchical Clustering on Principal Components were performed. Multivariate logistic regression was used to test for associations between HF profiles and injuries. RESULTS: The sample comprised 1467 patients (69% female, average age = 84.5 years). Five profiles were identified: youngest seniors who took risks and fell from a raised height, youngest seniors with specific health problems who fell down a stairs, autonomous seniors who fell because they lost their balance or fell from their own height, dependent seniors who fell during low-intensity activities, very old seniors for whom missing data were frequent. Fractures were more frequent among the first profile than the last two profiles constituted with more dependent individuals (p < 0.001). CONCLUSION: These results highlight the heterogeneity of the circumstances in which older people fall. A greater understanding of these circumstances is needed to implement targeted prevention actions.

Adherence to a Mediterranean diet and plasma fatty acids: data from the Bordeaux sample of the Three-City study.

Higher adherence to a Mediterranean diet (MeDi) and n-3 PUFA may both contribute to decreased dementia risk, but the association between MeDi adherence and lipid status is unclear. The aim of the present study was to analyse the relationship between plasma fatty acids and MeDi adherence in French elderly community dwellers. The study population (mean age 75·9 years) consisted of 1050 subjects from Bordeaux (France) included in the Three-City cohort. Adherence to the MeDi (scored as 0-9) was computed from a FFQ and 24 h recall. The proportion of each plasma fatty acid was determined. Cross-sectional analysis of the association between plasma fatty acids and MeDi adherence was performed by multi-linear regression. After adjusting for age, sex, energy intake, physical activity, smoking status, BMI, plasma TAG and apoE-ɛ4 genotype, plasma palmitoleic acid was significantly inversely associated with MeDi adherence, whereas plasma DHA, the EPA+DHA index and total n-3 PUFA were positively associated with MeDi adherence. The n-6:n-3 PUFA, arachidonic acid (AA):EPA, AA:DHA and AA:(EPA+DHA) ratios were significantly inversely associated with MeDi adherence. Plasma EPA was positively associated with MeDi adherence only in apoE-ɛ4 non-carriers. There was no association between MeDi adherence and SFA and total MUFA. The present results suggest that the protective effect of the MeDi on cognitive functions might be mediated by higher plasma DHA and lower n-6:n-3 PUFA ratios.

Young-Onset Dementia Among Individuals With History of Preeclampsia.

This cohort study assesses the risk of developing early-onset dementia in individuals who had preeclampsia and other hypertensive disorders during pregnancy.

The association between physical and mental chronic conditions and napping.

The objectives of this study were to assess the associations among various physical and mental chronic conditions and napping. A cross-sectional epidemiological survey was proposed within the NutriNet-Santé population-based e-cohort launched in France in 2009. Participants were 43,060 French volunteers aged 18 y and over with Internet access. A self-report questionnaire assessing sleep characteristics was administered in 2014. The main outcome (dependent) variable was weekday or weekend napping (yes/no). The main exposure (independent) variables were overweight/obesity, hypertension, diabetes, anxiety and depressive disorders, incident major cardiovascular diseases (myocardial infarction, stroke, unstable angina), and incident cancer (breast and prostate). The associations of interest were investigated with multivariable logistic regression analysis. No significant associations were found between major cardiovascular diseases or breast or prostate cancer and napping. Instead, we found that napping was more common among males (46.1%) than among females 36.9% (p < 0.0001). Individuals who were overweight or obese or had hypertension, diabetes, depression or anxiety disorders had an increased likelihood of napping compared with their healthy peers. The adjusted ORs ranged from 1.14 to 1.28″. In conclusion, most chronic conditions were independently associated with napping. Future longitudinal analyses are needed to elucidate causality.

Associations between usual diet and gut microbiota composition: results from the Milieu Intérieur cross-sectional study.

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

Food consumption and dietary intakes in 36,448 adults and their association with irritable bowel syndrome: Nutrinet-Santé study.

INTRODUCTION: Diet plays an important role for patients with irritable bowel syndrome (IBS). The aim of this study was to compare the diets in terms of food consumption and nutrient intake between subjects with IBS and controls in a large French population. METHODS: This study included 36,448 subjects from the Nutrinet-Santé cohort study, who completed a questionnaire pertaining to functional bowel disorders based on the Rome III criteria. Dietary data were obtained from at least three self-administered 24 h records via the internet. Association between IBS and diet was evaluated by comparison tests controlled for gender, age and total energy intake (ANCOVA tests). RESULTS: Subjects included were mainly women (76.9%) and the mean age was 50.2 ± 14.2 years. Among these individuals, 1870 (5.1%) presented with IBS. Compared to healthy controls, they had significantly lower consumption of milk (74.6 versus 88.4 g/day; p < 0.0001), yogurt (108.4 versus 115.5 g/day; p = 0.001), fruits (192.3 versus 203.8 g/day; p < 0.001), and higher soft non-sugared beverages (1167.2 versus 1122.9 ml/day; p < 0.001). They had higher total energy intake (2028.9 versus 1995.7 kcal/day; p < 0.001), with higher intakes of lipids (38.5 versus 38.1% of total energy intake; p = 0.001) and lower intakes of proteins (16.4 versus 16.8% of total energy intake; p < 0.0001), as well as micronutrients (calcium, potassium, zinc and vitamins B2, B5 and B9, all p < 0.0001). CONCLUSIONS: In this large sample, these findings suggest that dietary intake of subjects suffering from IBS differs from that of control subjects. They may have adapted their diet according to symptoms following medical or non-medical recommendations.

Association between self-reported vegetarian diet and the irritable bowel syndrome in the French NutriNet cohort.

BACKGROUND: There is growing interest in using diet counselling in the management of patients with irritable bowel syndrome (IBS). Among new emerging diets, vegetarian diets (VD) seem to be experiencing an important popularity, partly because of their alleged health benefits. A recent study performed among a rural Indian population showed that predominant VD could be associated with IBS. OBJECTIVE: This cross-sectional study aimed at assessing the association between the VD and IBS, among a large French cohort, the NutriNet-santé study. METHODS: Subjects participating in the NutriNet-Santé cohort study completed a questionnaire based on Rome III criteria (N = 41,682). Anthropometrics, socio-demographical and lifestyle data, including VD, were collected prior to the completion of Rome III questionnaire via self-administered questionnaires. Association between VD and IBS and its subtypes was investigated through multivariate logistic regression. RESULTS: The included subjects were mainly women (78.0%) and the mean age was 49.8±14.3 years. Among these individuals, 2,264 (5.4%) presented an IBS, and 805 (1.9%) reported a VD. Overall, VD was not associated with IBS or subtypes. A stable VD (i.e. self-declared at least three times) was associated with IBS (aOR 2.60 95%CI [1.37-4.91]), IBS mixed (aOR 2.97 95%CI [1.20-7.36]) and IBS diarrhoea (aOR 2.77 95%CI [1.01-7.59]). CONCLUSIONS: This study suggests that a long term VD could be associated with IBS. Nevertheless, further studies are needed to confirm these results, and investigate the multiple aspects of the vegetarian diet, possibly related to the IBS.

Nutritional status in community-dwelling elderly in France in urban and rural areas.

UNLABELLED: Malnutrition is a frequent condition in elderly people, especially in nursing homes and geriatric wards. Its frequency is less well known among elderly living at home. The objective of this study was to describe the nutritional status evaluated by the Mini Nutritional Assessment (MNA) of elderly community-dwellers living in rural and urban areas in France and to investigate its associated factors. METHODS: Subjects aged 65 years and over from the Approche Multidisciplinaire Intégrée (AMI) cohort (692 subjects living in a rural area) and the Three-City (3C) cohort (8,691 subjects living in three large urban zones) were included. A proxy version of the MNA was reconstructed using available data from the AMI cohort. Sensitivity and specificity were used to evaluate the agreement between the proxy version and the standard version in AMI. The proxy MNA was computed in both cohorts to evaluate the frequency of poor nutritional status. Factors associated with this state were investigated in each cohort separately. RESULTS: In the rural sample, 38.0% were females and the mean age was 75.5 years. In the urban sample, 60.3% were females and the mean age was 74.1 years. Among subjects in living in the rural sample, 7.4% were in poor nutritional status while the proportion was 18.5% in the urban sample. Female gender, older age, being widowed, a low educational level, low income, low body mass index, being demented, having a depressive symptomatology, a loss of autonomy and an intake of more than 3 drugs appeared to be independently associated with poor nutritional status. CONCLUSION: Poor nutritional status was commonly observed among elderly people living at home in both rural and urban areas. The associated factors should be further considered for targeting particularly vulnerable individuals.