Association of dietary and nutritional factors with cognitive decline, dementia, and depressive symptomatology in older individuals according to a neurogenesis-centred biological susceptibility to brain ageing.

Hippocampal neurogenesis (HN) occurs throughout the life course and is important for memory and mood. Declining with age, HN plays a pivotal role in cognitive decline (CD), dementia, and late-life depression, such that altered HN could represent a neurobiological susceptibility to these conditions. Pertinently, dietary patterns (e.g., Mediterranean diet) and/or individual nutrients (e.g., vitamin D, omega 3) can modify HN, but also modify risk for CD, dementia, and depression. Therefore, the interaction between diet/nutrition and HN may alter risk trajectories for these ageing-related brain conditions. Using a subsample (n = 371) of the Three-City cohort-where older adults provided information on diet and blood biobanking at baseline and were assessed for CD, dementia, and depressive symptomatology across 12 years-we tested for interactions between food consumption, nutrient intake, and nutritional biomarker concentrations and neurogenesis-centred susceptibility status (defined by baseline readouts of hippocampal progenitor cell integrity, cell death, and differentiation) on CD, Alzheimer's disease (AD), vascular and other dementias (VoD), and depressive symptomatology, using multivariable-adjusted logistic regression models. Increased plasma lycopene concentrations (OR [95% CI] = 1.07 [1.01, 1.14]), higher red meat (OR [95% CI] = 1.10 [1.03, 1.19]), and lower poultry consumption (OR [95% CI] = 0.93 [0.87, 0.99]) were associated with an increased risk for AD in individuals with a neurogenesis-centred susceptibility. Increased vitamin D consumption (OR [95% CI] = 1.05 [1.01, 1.11]) and plasma γ-tocopherol concentrations (OR [95% CI] = 1.08 [1.01, 1.18]) were associated with increased risk for VoD and depressive symptomatology, respectively, but only in susceptible individuals. This research highlights an important role for diet/nutrition in modifying dementia and depression risk in individuals with a neurogenesis-centred susceptibility.

Factors driving the inter-individual variability in the metabolism and bioavailability of (poly)phenolic metabolites: A systematic review of human studies.

This systematic review provides an overview of the available evidence on the inter-individual variability (IIV) in the absorption, distribution, metabolism, and excretion (ADME) of phenolic metabolites and its determinants. Human studies were included investigating the metabolism and bioavailability of (poly)phenols and reporting IIV. One hundred fifty-three studies met the inclusion criteria. Inter-individual differences were mainly related to gut microbiota composition and activity but also to genetic polymorphisms, age, sex, ethnicity, BMI, (patho)physiological status, and physical activity, depending on the (poly)phenol sub-class considered. Most of the IIV has been poorly characterised. Two major types of IIV were observed. One resulted in metabolite gradients that can be further classified into high and low excretors, as seen for all flavonoids, phenolic acids, prenylflavonoids, alkylresorcinols, and hydroxytyrosol. The other type of IIV is based on clusters of individuals defined by qualitative differences (producers vs. non-producers), as for ellagitannins (urolithins), isoflavones (equol and O-DMA), resveratrol (lunularin), and preliminarily for avenanthramides (dihydro-avenanthramides), or by quali-quantitative metabotypes characterized by different proportions of specific metabolites, as for flavan-3-ols, flavanones, and even isoflavones. Future works are needed to shed light on current open issues limiting our understanding of this phenomenon that likely conditions the health effects of dietary (poly)phenols.

A Systematic Review and Comprehensive Evaluation of Human Intervention Studies to Unravel the Bioavailability of Hydroxycinnamic Acids.

Significance: Hydroxycinnamic acids (HCAs) are the main phenolic acids in the western diet. Harmonizing the available information on the absorption, distribution, metabolism, and excretion (ADME) of HCAs is fundamental to unraveling the compounds responsible for their health effects. This work systematically assessed pharmacokinetics, including urinary recovery, and bioavailability of HCAs and their metabolites, based on literature reports. Recent Advances: Forty-seven intervention studies with coffee, berries, herbs, cereals, tomato, orange, grape products, and pure compounds, as well as other sources yielding HCA metabolites, were included. Up to 105 HCA metabolites were collected, mainly acyl-quinic and C6-C3 cinnamic acids. C6-C3 cinnamic acids, such as caffeic and ferulic acid, reached the highest blood concentrations (maximum plasma concentration [Cmax] = 423 nM), with time to reach Cmax (Tmax) values ranging from 2.7 to 4.2 h. These compounds were excreted in urine in higher amounts than their phenylpropanoic acid derivatives (4% and 1% of intake, respectively), but both in a lower percentage than hydroxybenzene catabolites (11%). Data accounted for 16 and 18 main urinary and blood HCA metabolites, which were moderately bioavailable in humans (collectively 25%). Critical Issues: A relevant variability emerged. It was not possible to unequivocally assess the bioavailability of HCAs from each ingested source, and data from some plant based-foods were absent or inconsistent. Future Directions: A comprehensive study investigating the ADME of HCAs derived from their most important dietary sources is urgently required. Eight key metabolites were identified and reached interesting plasma Cmax concentrations and urinary recoveries, opening up new perspectives to evaluate their bioactivity at physiological concentrations. Antioxid. Redox Signal. 40, 510-541.

A Mediterranean Diet-Based Metabolomic Score and Cognitive Decline in Older Adults: A Case-Control Analysis Nested within the Three-City Cohort Study.

SCOPE: Evidence on the Mediterranean diet (MD) and age-related cognitive decline (CD) is still inconclusive partly due to self-reported dietary assessment. The aim of the current study is to develop an MD- metabolomic score (MDMS) and investigate its association with CD in community-dwelling older adults. METHODS AND RESULTS: This study includes participants from the Three-City Study from the Bordeaux (n = 418) and Dijon (n = 422) cohorts who are free of dementia at baseline. Repeated measures of cognition over 12 years are collected. An MDMS is designed based on serum biomarkers related to MD key food groups and using a targeted metabolomics platform. Associations with CD are investigated through conditional logistic regression (matched on age, sex, and education level) in both sample sets. The MDMS is found to be inversely associated with CD (odds ratio [OR] [95% confidence interval (CI)] = 0.90 [0.80-1.00]; p = 0.048) in the Bordeaux (discovery) cohort. Results are comparable in the Dijon (validation) cohort, with a trend toward significance (OR [95% CI] = 0.91 [0.83-1.01]; p = 0.084). CONCLUSIONS: A greater adherence to the MD, here assessed by a serum MDMS, is associated with lower odds of CD in older adults.

Systematic Review on the Metabolic Interest of Glucosinolates and Their Bioactive Derivatives for Human Health.

In the last decade, most of the evidence on the clinical benefits of including cruciferous foods in the diet has been focused on the content of glucosinolates (GSL) and their corresponding isothiocyanates (ITC), and mercapturic acid pathway metabolites, based on their capacity to modulate clinical, biochemical, and molecular parameters. The present systematic review summarizes findings of human studies regarding the metabolism and bioavailability of GSL and ITC, providing a comprehensive analysis that will help guide future research studies and facilitate the consultation of the latest advances in this booming and less profusely researched area of GSL for food and health. The literature search was carried out in Scopus, PubMed and the Web of Science, under the criteria of including publications centered on human subjects and the use of Brassicaceae foods in different formulations (including extracts, beverages, and tablets), as significant sources of bioactive compounds, in different types of subjects, and against certain diseases. Twenty-eight human intervention studies met inclusion criteria, which were classified into three groups depending on the dietary source. This review summarizes recent studies that provided interesting contributions, but also uncovered the many potential venues for future research on the benefits of consuming cruciferous foods in our health and well-being. The research will continue to support the inclusion of GSL-rich foods and products for multiple preventive and active programs in nutrition and well-being.

Monoterpenes: current knowledge on food source, metabolism, and health effects.

Monoterpenes, volatile metabolites produced by plants, are involved in the taste and aroma perception of fruits and vegetables and have been used for centuries in gastronomy, as food preservatives and for therapeutic purposes. Biological activities such as antimicrobial, analgesic and anti-inflammatory are well-established for some of these molecules. More recently, the ability of monoterpenes to regulate energy metabolism, and exert antidiabetic, anti-obesity and gut microbiota modulation activities have been described. Despite their promising health effects, the lack of reliable quantification of monoterpenes in food, hindered the investigation of their role as dietary bioactive compounds in epidemiological studies. Moreover, only few studies have documented the biotransformation of these compounds and identified the monoterpene metabolites with biological activity. This review presents up-to-date knowledge about the occurrence of monoterpenes in food, their bioavailability and potential role in the modulation of intermediate metabolism and inflammation, focusing on novel findings of molecular mechanisms, underlining research gaps and new avenues to be explored.

Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis.

This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary flavan-3-ols and their circulating metabolites in healthy subjects. Literature searches were performed in PubMed, Scopus and the Web of Science. Human intervention studies using single and/or multiple intake of flavan-3-ols from food, extracts, and pure compounds were included. Forty-nine human intervention studies met inclusion criteria. Up to 180 metabolites were quantified from blood and urine samples following intake of flavan-3-ols, mainly as phase 2 conjugates of microbial catabolites (n = 97), with phenyl-γ-valerolactones being the most representative ones (n = 34). Phase 2 conjugates of monomers and phenyl-γ-valerolactones, the main compounds in both plasma and urine, reached two peak plasma concentrations (Cmax) of 260 and 88 nmol/L at 1.8 and 5.3 h (Tmax) after flavan-3-ol intake. They contributed to the bioavailability of flavan-3-ols for over 20%. Mean bioavailability for flavan-3-ols was moderate (31 ± 23%, n bioavailability values = 20), and it seems to be scarcely affected by the amount of ingested compounds. While intra- and inter-source differences in flavan-3-ol bioavailability emerged, mean flavan-3-ol bioavailability was 82% (n = 1) and 63% (n = 2) after (-)-epicatechin and nut (hazelnuts, almonds) intake, respectively, followed by 25% after consumption of tea (n = 7), cocoa (n = 5), apples (n = 3) and grape (n = 2). This highlights the need to better clarify the metabolic yield with which monomer flavan-3-ols and proanthocyanidins are metabolized in humans. This work clarified in a comprehensive way for the first time the ADME of a (poly)phenol family, highlighting the pool of circulating compounds that might be determinants of the putative beneficial effects linked to flavan-3-ol intake. Lastly, methodological inputs for implementing well-designed human and experimental model studies were provided.

Exploration of the Gut-Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons.

The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut−brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case−control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.

Impaired hippocampal neurogenesis in vitro is modulated by dietary-related endogenous factors and associated with depression in a longitudinal ageing cohort study.

Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels - both of which are closely linked to diet - all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.

Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline.

BACKGROUND: Fatty acids play prominent roles in brain function as they participate in structural, metabolic and signaling processes. The homeostasis of fatty acids and related pathways is known to be impaired in cognitive decline and dementia, but the relationship between these metabolic disturbances and common risk factors, namely the ɛ4 allele of the apolipoprotein E (ApoE-ɛ4) gene and sex, remains elusive. METHODS: In order to investigate early alterations associated with cognitive decline in the fatty acid-related serum metabolome, we here applied targeted metabolomics analysis on a nested case-control study (N=368), part of a prospective population cohort on dementia. RESULTS: When considering the entire study population, circulating levels of free fatty acids, acyl-carnitines and pantothenic acid were found to be increased among those participants who had greater odds of cognitive decline over a 12-year follow-up. Interestingly, stratified analyses indicated that these metabolomic alterations were specific for ApoE-ɛ4 non-carriers and women. CONCLUSIONS: Altogether, our results highlight that the regulation of fatty acids and related metabolic pathways during ageing and cognitive decline depends on complex inter-relationships between the ApoE-ε4 genotype and sex. A better understanding of the ApoE-ɛ4 and sex dependent modulation of metabolism is essential to elucidate the individual variability in the onset of cognitive decline, which would help develop personalized therapeutic approaches.

The serum metabolome mediates the concert of diet, exercise, and neurogenesis, determining the risk for cognitive decline and dementia.

INTRODUCTION: Diet and exercise influence the risk of cognitive decline (CD) and dementia through the food metabolome and exercise-triggered endogenous factors, which use the blood as a vehicle to communicate with the brain. These factors might act in concert with hippocampal neurogenesis (HN) to shape CD and dementia. METHODS: Using an in vitro neurogenesis assay, we examined the effects of serum samples from a longitudinal cohort (n = 418) on proxy HN readouts and their association with future CD and dementia across a 12-year period. RESULTS: Altered apoptosis and reduced hippocampal progenitor cell integrity were associated with exercise and diet and predicted subsequent CD and dementia. The effects of exercise and diet on CD specifically were mediated by apoptosis. DISCUSSION: Diet and exercise might influence neurogenesis long before the onset of CD and dementia. Alterations in HN could signify the start of the pathological process and potentially represent biomarkers for CD and dementia.

Food and Microbiota Metabolites Associate with Cognitive Decline in Older Subjects: A 12-Year Prospective Study.

SCOPE: Diet is considered an important modulator of cognitive decline and dementia, but the available evidence is, however, still fragmented and often inconsistent. METHODS AND RESULTS: The article studies the long-term prospective Three-City Cohort, which consists of two separate nested case-control sample sets from different geographic regions (Bordeaux, n = 418; Dijon, n = 424). Cognitive decline is evaluated through five neuropsychological tests (Mini-Mental State Examination, Benton Visual Retention Test, Isaac's Set Test, Trail-Making Test part A, and Trail-Making Test part B). The food-related and microbiota-derived circulating metabolome is studied in participants free of dementia at baseline, by subjecting serum samples to large-scale quantitative metabolomics analysis. A protective association is found between metabolites derived from cocoa, coffee, mushrooms, red wine, the microbial metabolism of polyphenol-rich foods, and cognitive decline, as well as a negative association with metabolites related to unhealthy dietary components, such as artificial sweeteners and alcohol. CONCLUSION: These results provide insight into the early metabolic events that are associated with the later risk to develop cognitive decline within the crosstalk between diet, gut microbiota and the endogenous metabolism, which can help identify potential targets for preventive and therapeutic strategies to preserve cognitive health.

Data sharing in PredRet for accurate prediction of retention time: Application to plant food bioactive compounds.

Prediction of retention times (RTs) is increasingly considered in untargeted metabolomics to complement MS/MS matching for annotation of unidentified peaks. We tested the performance of PredRet (http://predret.org/) to predict RTs for plant food bioactive metabolites in a data sharing initiative containing entry sets of 29-103 compounds (totalling 467 compounds, >30 families) across 24 chromatographic systems (CSs). Between 27 and 667 predictions were obtained with a median prediction error of 0.03-0.76 min and interval width of 0.33-8.78 min. An external validation test of eight CSs showed high prediction accuracy. RT prediction was dependent on shape and type of LC gradient, and number of commonly measured compounds. Our study highlights PredRet's accuracy and ability to transpose RT data acquired from one CS to another CS. We recommend extensive RT data sharing in PredRet by the community interested in plant food bioactive metabolites to achieve a powerful community-driven open-access tool for metabolomics annotation.

Early signature in the blood lipidome associated with subsequent cognitive decline in the elderly: A case-control analysis nested within the Three-City cohort study.

BACKGROUND: Brain lipid metabolism appears critical for cognitive aging, but whether alterations in the lipidome relate to cognitive decline remains unclear at the system level. METHODS: We studied participants from the Three-City study, a multicentric cohort of older persons, free of dementia at time of blood sampling, and who provided repeated measures of cognition over 12 subsequent years. We measured 189 serum lipids from 13 lipid classes using shotgun lipidomics in a case-control sample on cognitive decline (matched on age, sex and level of education) nested within the Bordeaux study center (discovery, n = 418). Associations with cognitive decline were investigated using bootstrapped penalized regression, and tested for validation in the Dijon study center (validation, n = 314). FINDINGS: Among 17 lipids identified in the discovery stage, lower levels of the triglyceride TAG50:5, and of four membrane lipids (sphingomyelin SM40:2,2, phosphatidylethanolamine PE38:5(18:1/20:4), ether-phosphatidylethanolamine PEO34:3(16:1/18:2), and ether-phosphatidylcholine PCO34:1(16:1/18:0)), and higher levels of PCO32:0(16:0/16:0), were associated with greater odds of cognitive decline, and replicated in our validation sample. INTERPRETATION: These findings indicate that in the blood lipidome of non-demented older persons, a specific profile of lipids involved in membrane fluidity, myelination, and lipid rafts, is associated with subsequent cognitive decline. FUNDING: The complete list of funders is available at the end of the manuscript, in the Acknowledgement section.

Metabolomic Changes after Coffee Consumption: New Paths on the Block.

SCOPE: Several studies suggest that regular coffee consumption may help preventing chronic diseases, but the impact of daily intake and the contribution of coffee metabolites in disease prevention are still unclear. The present study aims at evaluating whether and how different patterns of coffee intake (one cup of espresso coffee/day, three cups of espresso coffee/day, and one cup of espresso coffee/day and two cocoa-based products containing coffee two times per day) may impact endogenous molecular pathways. METHODS AND RESULTS: A three-arm, randomized, crossover trial is performed in 21 healthy volunteers who consumed each treatment for one month. Urine samples are collected to perform untargeted metabolomics based on UHPLC-IMS-HRMS. A total of 153 discriminant metabolites are identified. Several molecular features are associated with coffee consumption, while others are linked with different metabolic pathways, such as phenylalanine, tyrosine, energy metabolism, steroid hormone biosynthesis, and arginine biosynthesis and metabolism. CONCLUSION: This information has provided new insights into the metabolic routes by which coffee and coffee-related metabolites may exert effects on human health.

Caffeine Compromises Proliferation of Human Hippocampal Progenitor Cells.

The age-associated reduction in the proliferation of neural stem cells (NSCs) has been associated with cognitive decline. Numerous factors have been shown to modulate this process, including dietary components. Frequent consumption of caffeine has been correlated with an increased risk of cognitive decline, but further evidence of a negative effect on hippocampal progenitor proliferation is limited to animal models. Here, we used a human hippocampal progenitor cell line to investigate the effects of caffeine on hippocampal progenitor integrity and proliferation specifically. The effects of five caffeine concentrations (0 mM = control, 0.1 mM ∼ 150 mg, 0.25 mM ∼ 400 mg, 0.5 mM ∼ 750 mg, and 1.0 mM ∼ 1500 mg) were measured following acute (1 day) and repeated (3 days) exposure. Immunocytochemistry was used to quantify hippocampal progenitor integrity (i.e., SOX2- and Nestin-positive cells), proliferation (i.e., Ki67-positive cells), cell count (i.e., DAPI-positive cells), and apoptosis (i.e., CC3-positive cells). We found that progenitor integrity was significantly reduced in supraphysiological caffeine conditions (i.e., 1.0 mM ∼ 1500 mg), but relative to the lowest caffeine condition (i.e., 0.1 mM ∼ 150 mg) only. Moreover, repeated exposure to supraphysiological caffeine concentrations (i.e., 1.0 mM ∼ 1500 mg) was found to affect proliferation, significantly reducing % Ki67-positive cells relative to control and lower caffeine dose conditions (i.e., 0.1 mM ∼ 150 mg and 0.25 mM ∼ 400 mg). Caffeine treatment did not influence apoptosis and there were no significant differences in any measure between lower doses of caffeine (i.e., 0.1 mM, 0.25 mM, 0.5 mM) - representative of daily human caffeine intake - and control conditions. Our study demonstrates that dietary components such as caffeine can influence NSC integrity and proliferation and may be indicative of a mechanism by which diet affects cognitive outcomes.

Recommendations for standardizing nomenclature for dietary (poly)phenol catabolites.

There is a lack of focus on the protective health effects of phytochemicals in dietary guidelines. Although a number of chemical libraries and databases contain dietary phytochemicals belonging to the plant metabolome, they are not entirely relevant to human health because many constituents are extensively metabolized within the body following ingestion. This is especially apparent for the highly abundant dietary (poly)phenols, for which the situation is compounded by confusion regarding their bioavailability and metabolism, partially because of the variety of nomenclatures and trivial names used to describe compounds arising from microbial catabolism in the gastrointestinal tract. This confusion, which is perpetuated in online chemical/metabolite databases, will hinder future discovery of bioactivities and affect the establishment of future dietary guidelines if steps are not taken to overcome these issues. In order to resolve this situation, a nomenclature system for phenolic catabolites and their human phase II metabolites is proposed in this article and the basis of its format outlined. Previous names used in the literature are cited along with the recommended nomenclature, International Union of Pure and Applied Chemistry terminology, and, where appropriate, Chemical Abstracts Service numbers, InChIKey, and accurate mass.

Food intake biomarkers for green leafy vegetables, bulb vegetables, and stem vegetables: a review.

BACKGROUND: Numerous studies acknowledged the importance of an adequate vegetable consumption for human health. However, current methods to estimate vegetable intake are often prone to measurement errors due to self-reporting and/or insufficient detail. More objective intake biomarkers for vegetables, using biological specimens, are preferred. The only concentration biomarkers currently available are blood carotenoids and vitamin C, covering total fruit and vegetable intake. Identification of biomarkers for specific vegetables is needed for a better understanding of their relative importance for human health. Within the FoodBAll Project under the Joint Programming Initiative "A Healthy Diet for a Healthy Life", an ambitious action was undertaken to identify candidate intake biomarkers for all major food groups consumed in Europe by systematically reviewing the existent literature. This study describes the review on candidate biomarkers of food intake (BFIs) for leafy, bulb, and stem vegetables, which was conducted within PubMed, Scopus and Web of Science for studies published through March 2019. RESULTS: In total, 65 full-text articles were assessed for eligibility for leafy vegetables, and 6 full-text articles were screened for bulb and stem vegetables. Putative BFIs were identified for spinach, lettuce, endive, asparagus, artichoke, and celery, but not for rocket salad. However, after critical evaluation through a validation scheme developed by the FoodBAll consortium, none of the putative biomarkers appeared to be a promising BFI. The food chemistry data indicate that some candidate BFIs may be revealed by further studies. CONCLUSION: Future randomized controlled feeding studies combined with observational studies, applying a non-targeted metabolomics approach, are needed in order to identify valuable BFIs for the intake of leafy, bulb, and stem vegetables.

Why interindividual variation in response to consumption of plant food bioactives matters for future personalised nutrition.

Food phytochemicals are increasingly considered to play a key role in the cardiometabolic health effects of plant foods. However, the heterogeneity in responsiveness to their intake frequently observed in clinical trials can hinder the beneficial effects of these compounds in specific subpopulations. A range of factors, including genetic background, gut microbiota, age, sex and health status, could be involved in these interindividual variations; however, the current knowledge is limited and fragmented. The European network, European Cooperation in Science and Technology (COST)-POSITIVe, has analysed, in a systematic way, existing knowledge with the aim to better understand the factors responsible for the interindividual variation in response to the consumption of the major families of plant food bioactives, regarding their bioavailability and bioefficacy. If differences in bioavailability, likely reflecting differences in human subjects' genetics or in gut microbiota composition and functionality, are believed to underpin much of the interindividual variability, the key molecular determinants or microbial species remain to be identified. The systematic analysis of published studies conducted to assess the interindividual variation in biomarkers of cardiometabolic risk suggested some factors (such as adiposity and health status) as involved in between-subject variation. However, the contribution of these factors is not demonstrated consistently across the different compounds and biological outcomes and would deserve further investigations. The findings of the network clearly highlight that the human subjects' intervention studies published so far are not adequate to investigate the relevant determinants of the absorption/metabolism and biological responsiveness. They also emphasise the need for a new generation of intervention studies designed to capture this interindividual variation.

Untargeted plasma metabolomic profiles associated with overall diet in women from the SU.VI.MAX cohort.

PURPOSE: Dietary intakes are reflected in plasma by the presence of hundreds of exogenous metabolites and variations in endogenous metabolites. The exploration of diet-related plasma metabolic profiles could help to better understand the impact of overall diet on health. Our aim was to identify metabolomic signatures reflecting overall diet in women from the French general population. METHODS: This cross-sectional study included 160 women in the SU.VI.MAX cohort with detailed dietary data (≥ 10 24-h dietary records) selected according to their level of adherence to the French dietary recommendations, represented by the validated score mPNNS-GS; 80 women from the 10th decile of the score were matched with 80 women from the 1st decile. Plasma metabolomic profiles were acquired using untargeted UPLC-QToF mass spectrometry analysis. The associations between metabolomic profiles and the mPNNG-GS, its components and Principal Component Analyses-derived dietary patterns were investigated using multivariable conditional logistic regression models and partial correlations. RESULTS: Adherence to the dietary recommendations was positively associated with 3-indolepropionic acid and pipecolic acid (also positively associated with fruit and vegetable intake and a healthy diet)-2 metabolites linked to microbiota and inversely associated with lysophosphatidylcholine (LysoPC(17:1)), acylcarnitine C9:1 (also inversely associated with a healthy diet), acylcarnitine C11:1 and 2-deoxy-D-glucose. Increased plasma levels of piperine and Dihydro4mercapto-3(2H) furanone were observed in women who consumed a Western diet and a healthy diet, respectively. Ethyl-ß-D-glucopyranoside was positively associated with alcohol intake. Plasma levels of LysoPC(17:1), cholic acid, phenylalanine-phenylalanine and phenylalanine and carnitine C9:1 decreased with the consumption of vegetable added fat, sweetened food, milk and dairy products and fruit and vegetable intakes, respectively. CONCLUSION: This study highlighted several metabolites from both host and microbial metabolism reflecting the long-term impact of the overall diet. TRIAL REGISTRATION: SU.VI.MAX, clinicaltrials.gov NCT00272428. Registered 3 January 2006, https://clinicaltrials.gov/show/NCT00272428.