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The association between 25-hydroxyvitamin D and 5-, 10-, or 15-year weight change were assessed in a population-based, prospective study conducted in Lausanne, Switzerland. Data from the first (2009-2012, N = 3527, 51.3% women), second (2014-2017, N = 3237, 53.8% women), and third (2018-2021, N = 2567, 54.2% women) follow-ups were used. A weighted genetic risk score (GRS) of 115 SNPs associated with vitamin D levels was constructed. At baseline, the GRS correlated positively with 25-hydroxyvitamin D levels based on a Spearman rank correlation and 95% confidence interval: 0.198 (0.166; 0.231)

There are limited data on the prevalence of anaemia and iron deficiency (ID) in Somalia. To address this data gap, Somalia's 2019 micronutrient survey assessed the prevalence of anaemia and ID in children (6–59 months) and non‐pregnant women of reproductive age (15–49 years). The survey also collected data on vitamin A deficiency, inflammation, malaria and other potential risk factors for anaemia and ID. Multivariable Poisson regressions models were used to identify the risk factors for anaemia and ID in children and women. Among children, the prevalence of anaemia and ID were 43.4% and 47.2%, respectively. Approximately 36% and 6% of anaemia were attributable to iron and vitamin A deficiencies, respectively, whereas household possession of soap was associated with approximately 11% fewer cases of anaemia. ID in children was associated with vitamin A deficiency and stunting, whereas inflammation was associated with iron sufficiency. Among women, 40.3% were anaemic, and 49.7% were iron deficient. In women, ID and number of births were significantly associated with anaemia in multivariate models, and approximately 42% of anaemia in women was attributable to ID. Increased parity was associated with ID, and incubation and early convalescent inflammation was associated with ID, whereas late convalescent inflammation was associated with iron sufficiency. ID is the main risk factor of anaemia in both women and children and contributed to a substantial portion of the anaemia cases. To tackle both anaemia and ID in Somalia, food assistance and micronutrient‐specific programmes (e.g. micronutrient powders and iron supplements) should be enhanced.

Steady hematopoiesis is essential for lifelong production of all mature blood cells. Hematopoietic stem and progenitor cells (HSPCs) found in the bone marrow ensure hematopoietic homeostasis in an organism. Failure of this complex process, which involves a fine balance of self-renewal and differentiation fates, often result in severe hematological conditions such as leukemia and lymphoma. Several molecular and metabolic programs, internal or in close interaction with the bone marrow niche, have been identified as important regulators of HSPC function. More recently, nutrient sensing pathways have emerged as important modulators of HSC homing, dormancy, and function in the bone marrow. Here we describe a method for reliable measurement of various amino acids and minerals in different rare bone marrow (BM) populations, namely HSPCs. We found that the amino acid profile of the most primitive hematopoietic compartments (KLS) did not differ significantly from the one of their direct progenies (common myeloid progenitor CMP), while granulocyte-monocyte progenitors (GMPs), on the opposite of megakaryocyte-erythroid progenitors (MEPs), have higher content of the majority of amino acids analyzed. Additionally, we identified intermediates of the urea cycle to be differentially expressed in the KLS population and were found to lower mitochondrial membrane potential, an established readout on self-renewal capability. Moreover, we were able to profile for the first time 12 different minerals and detect differences in elemental contents between different HSPC compartments. Importantly, essential dietary trace elements, such as iron and molybdenum, were found to be enriched in granulocyte-monocyte progenitors (GMPs). We envision this amino acid and mineral profiling will allow identification of novel metabolic and nutrient sensing pathways important in HSPC fate regulation.

Supplemental Digital Content is available in the text, Introduction: Intensive care unit-acquired weakness (ICU-AW) is often observed in critically ill patients with prolonged intensive care unit (ICU) stay. We hypothesized that evolving metabolic abnormalities during prolonged ICU stay are reflected by changing nutrient patterns in blood, urine and skeletal muscle, and that these patterns differ in patients with/without ICU-AW and between patients with/without sepsis. Methods: In a prospective single-center observational trial, we aim to recruit 100 critically ill patients (ICU length of stay ≥ 5 days) with severe sepsis/septic shock (“sepsis group”, n = 50) or severe head trauma/intracerebral hemorrhage (“CNS group”, n = 50). Patients will be sub-grouped for presence or absence of ICU-AW as determined by the Medical Research Council sum score. Blood and urine samples will be collected and subjected to comprehensive nutrient analysis at different time points by targeted quantitative mass spectrometric methods. In addition, changes in muscular tissue (biopsy, when available), muscular architecture (ultrasound), electrophysiology, body composition analyses (bioimpedance, cerebral magnetic resonance imaging), along with clinical status will be assessed. Patients will be followed-up for 180 and 360 days including assessment of quality of life. Discussion: Key objective of this trial is to assess changes in nutrient pattern in blood and urine over time in critically ill patients with/without ICU-AW by using quantitative nutrient analysis techniques. Peer-reviewed published NAChO data will allow for a better understanding of metabolic changes in critically ill patients on standard liquid enteral nutrition and will likely open up new avenues for future therapeutic and nutritional interventions.

We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The (1)H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of β-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, α-keto-β-methylvalerate and α-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism.

Social and psychological stressors are both a part of daily life and are increasingly recognized as contributors to individual susceptibility to develop diseases and metabolic disorders. The present study investigated how snacks differing in sensory properties and presentation can influence ratings of affect in consumers with different levels of dispositional anxiety. This study examines the relationships between a pre-disposition to anxiety and food using a repeated exposures design with three interspersed test days over a period of two weeks. The study was conducted on ninety free-living male (n = 28) and female (n = 62) Dutch participants aged between 18 and 35 years old, with a BMI between 18 and 25 kg/m2 and different anxiety trait levels assessed using State-Trait Anxiety Inventory tests. The study was randomized by age, gender, anxiety trait score, and followed a parallel open design. Three test products: dark chocolate, a milk chocolate snack and crackers with cheese spread (control), which differed in composition, sensory properties and presentation, were evaluated. Changes in self-reported anxiety, emotion, and energetic states were assessed as a function of eating the snacks just after consumption and up to one hour. The repeated exposure design over a period of two weeks enabled the investigations of potential cumulative effects of regular consumption of the food products. The milk chocolate snack resulted in the decrease of anxiety in high anxiety trait subjects, whereas dark chocolate and cheese and crackers respectively improved the anxiety level and the energetic state of low anxiety trait participants. The mood effects were not altered with repeated exposure, and the magnitude of changes was similar on each test day, which illustrates the repeatability of the effects of the food on subjective measures of postprandial wellness.

High-resolution spectroscopic profiles of biofluids can define metabolic phenotypes, providing a window onto the impact of diet on health to reflect gene-environment interactions. (1)H NMR spectroscopic profiling was used to characterize the effect of nutritional intervention on the stability of the metabolic phenotype of 7 individuals following a controlled 7 day dietary protocol. Inter-individual metabolic differences influenced proportionally more of the spectrum than dietary modulation, with certain individuals displaying a greater stability of metabolic phenotypes than others. Correlation structures between urinary metabolites were identified and used to map inter-individual pathway differences. Choline degradation was the pathway most affected by the individual, suggesting that the gut microbiota influence host metabolic phenotypes. This influence was further emphasized by the highly correlated excretion of the microbial-mammalian co-metabolites phenylacetylglutamine, 4-cresylsulfate (r = 0.87), and indoxylsulfate (r = 0.67) across all individuals. Above the background of inter-individual differences, clear biochemical effects of single type dietary interventions, animal protein, fruit and wine intake, were observed; for example, the spectral variance introduced by fruit ingestion was attributed to the metabolites tartrate, proline betaine, hippurate, and 4-hydroxyhippurate. This differential metabolic baseline and response to selected dietary challenges highlights the importance of understanding individual differences in metabolism and provides a rationale for evaluating dietary interventions and stratification of individuals with respect to guiding nutrition and health programmes.

Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive. To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (bothP = 0·09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0·01 andP Clostridium leptumpopulations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0·096) and increased stool frequency (P

Dietary preferences influence basal human metabolism and gut microbiome activity that in turn may have long-term health consequences. The present study reports the metabolic responses of free living subjects to a daily consumption of 40 g of dark chocolate for up to 14 days. A clinical trial was performed on a population of 30 human subjects, who were classified in low and high anxiety traits using validated psychological questionnaires. Biological fluids (urine and blood plasma) were collected during 3 test days at the beginning, midtime and at the end of a 2 week study. NMR and MS-based metabonomics were employed to study global changes in metabolism due to the chocolate consumption. Human subjects with higher anxiety trait showed a distinct metabolic profile indicative of a different energy homeostasis (lactate, citrate, succinate, trans-aconitate, urea, proline), hormonal metabolism (adrenaline, DOPA, 3-methoxy-tyrosine) and gut microbial activity (methylamines, p-cresol sulfate, hippurate). Dark chocolate reduced the urinary excretion of the stress hormone cortisol and catecholamines and partially normalized stress-related differences in energy metabolism (glycine, citrate, trans-aconitate, proline, beta-alanine) and gut microbial activities (hippurate and p-cresol sulfate). The study provides strong evidence that a daily consumption of 40 g of dark chocolate during a period of 2 weeks is sufficient to modify the metabolism of free living and healthy human subjects, as per variation of both host and gut microbial metabolism.

Life stress promotes gut dysfunction, but underlying biochemical events are not well-understood. In the present study, we describe the metabolic events associated with background stress and its potential influence on the response to novel incoming stress stimulus in healthy subjects. A 15 min cold pain test was carried out in healthy men and women stratified according to low (LS; n = 21) and moderate background stress (MS; n = 9) during jejunal segmental perfusion. Cold pain induced a stronger psychological response in MS compared to LS subjects, but similar increases in heart rate and blood pressure. Urine and plasma were analyzed using 1H NMR-based metabonomics. Basal stress levels were imprinted in the metabolic profiles indicating different energy and lipid homeostasis. Cold pain increased gut permeability, as determined by mannitol and xylose levels, the response being greater in LS subjects. Moreover, the rate of plasma clearance of mannitol and xylose was dependent on background stress level and gender. In addition, cold pain modulated the levels of circulating ketone bodies, Krebs's cycle intermediates, glucose, and the glucogenic alanine and lactate, which brings further evidence of an alteration of energy homeostasis. Therefore, unravelling life stress with metabonomics may provide a system biology basis for the clinical management and therapeutic surveillance of gut health and disorders.

Symbiotic gut microbes can have a significant influence on host health and disease etiology. Here, we assessed the effects of inoculating germfree mice with human baby microbiota (HBM, n=17) on the biochemical composition of intact intestinal tissues (duodenum, jejunum, ileum, proximal and distal colon) using magic-angle-spinning 1H NMR spectroscopy. We compared the HBM tissue metabolite profiles with those from conventional (n=9) and conventionalized (n=10) mice. Each topographical intestinal region showed a specific metabolic profile that was altered differentially by the various microbiomes, especially for osmolytes. In each animal model, duodenum had higher ethanolamine and myo-inositol, and ileum higher taurine and betaine than other gut regions. HBM mice showed lower taurine and myo-inositol in the colon, and all ex-germfree animals had higher taurine, choline and ethanolamine in the jejunum. Interestingly, the jejunum of HBM mice was marked by a higher glutathione level and lower concentrations of its precursor methionine when compared to other groups. Proximal and distal colon tissues were differentiated in the different microbiome models by the concentrations of bacterial products (higher in conventional animals). These studies show the depth of gut microbiome modulations of the intestinal biochemistry.

Multicompartmental metabolic profiling combined with multivariate data analysis offers a unique opportunity to explore the multidimensional metabolic relationships between various biological matrices. Here, we applied unsupervised chemometric methods for integrating 1H NMR metabolic profiles from mouse plasma, liver, pancreas, adrenal gland and kidney cortex matrices in order to infer intercompartments functional links. Principal Component Analysis (PCA) revealed metabolic differences between matrices but contained limited information on intercompartment metabolic relationships. Multiway PCA enabled the assessment of interindividual metabolic variability across multiple compartments in a single model and, therefore, metabolic correlations between different organs and circulating biofluids. However, this approach does not provide information on the relative contribution of one compartment to another. Integration of metabolic profiles using Multivariate Curve Resolution (MCR) and Parallel Factor Analysis (PARAFAC) methods provided an overview of functional relationships across matrices and enabled the characterization of compartment-specific metabolite signatures, the spectrotypes. In particular, the spectrotypes describe biochemical profiles specific or common to different biological compartments. Consequently, MCR-ALS and PARAFAC appeared to be better adapted for stepwise variable and compartment selection for further correlation analysis. Such a combination of chemometric techniques could provide new research avenues to assess the efficacy of drug or nutritional interventions on targeted organs.

Coevolution shapes interorganismal crosstalk leading to profound and diverse cellular and metabolic changes as observed in gut dysbiosis in human diseases. Here, we modulated a simplified gut microbiota using pro-, pre-, and synbiotics to assess the depth of systemic metabolic exchanges in mice, using a multicompartmental modeling approach with metabolic signatures from 10 tissue/fluid compartments. The nutritionally induced microbial changes modulated host lipid, carbohydrate, and amino acid metabolism at a panorganismal scale. Galactosyl-oligosaccharides reduced lipogenesis, triacylglycerol incorporation into lipoproteins and triglyceride concentration in the liver and the kidney. Those changes were not correlated with decreased plasma lipoproteins that were specifically induced by L. rhamnosus supplementation. Additional alteration of transmethylation metabolic pathways (homocysteine-betaine) was observed in the liver and the pancreas following pre- and synbiotic microbial modulation, which may be of interest for control of glucose metabolism and insulin sensitivity. Probiotics also reduced hepatic glycogen and glutamine and adrenal ascorbate with inferred effects on energy homeostasis, antioxidation, and steroidogenesis. These studies show the breadth and the depth of gut microbiome modulations of host biochemistry and reveal that major mammalian metabolic processes are under symbiotic homeostatic control.

A lipidomic approach was employed in a clinically well-defined cohort of healthy obese women to explore blood lipidome phenotype ascribed to body fat deposition, with emphasis on epicardial adipose tissue (EAT).The present investigation delivered a lipidomics signature of epicardial adiposity under healthy clinical conditions using a cohort of 40 obese females (age: 25-45 years, BMI: 28-40 kg/m(2) ) not showing any metabolic disease traits. Lipidomics analysis of blood plasma was employed in combination with in vivo quantitation of mediastinal fat depots by computerized tomography.All cardiac fat depots correlated to indicators of hepatic dysfunctions (ALAT and ASAT), which describe physiological connections between hepatic and cardiac steatosis. Plasma lipidomics encompassed overall levels of lipid classes, fatty acid profiles, and individual lipid species. EAT and visceral fat associated with diacylglycerols (DAG), triglycerides, and distinct phospholipid and sphingolipid species. A pattern of DAG and phosphoglycerols was specific to EAT.Human blood plasma lipidomics appears to be a promising clinical and potentially diagnostic readout for patient stratification and monitoring. Association of blood lipidomics signature to regio-specific mediastinal and visceral adiposity under healthy clinical conditions may help provide more biological insights into obese patient stratification for cardiovascular disease risks.

As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

BACKGROUND: The combination of maternal obesity in early pregnancy and high protein intake in infant formula feeding might predispose to obesity risk in later life. METHODS: This study assesses the impact of breast- or formula-feeding (differing in protein content by 1.65 or 2.7g/100 kcal) on the metabolism of term infants from overweight and obese mothers. From birth to 3 mo of age, infants received exclusively either breast- or starter formula-feeding and until 6 mo, exclusively either a formula designed for this study or breast-feeding. From 6 to 12 mo, infants received complementary weaning food. Metabonomics was conducted on the infants' urine and stool samples collected at the age of 3, 6, and 12 mo. RESULTS: Infant formula-feeding resulted in higher protein-derived short-chain fatty acids and amino acids in stools. Urine metabonomics revealed a relationship between bacterial processing of dietary proteins and host protein metabolism stimulated with increasing protein content in the formula. Moreover, formula-fed infants were metabolically different from breast-fed infants, at the level of lipid and energy metabolism (carnitines, ketone bodies, and Krebs cycle). CONCLUSION: Noninvasive urine and stool metabolic monitoring of responses to early nutrition provides relevant readouts to assess nutritional requirements for infants' growth.

Increasing evidence points toward the critical and long-term involvement of prenatal and early nutrition and lifestyle on later health and disease risk predisposition. Metabolomics is now a well-established top-down systems biology approach that explores the genetic-environment-health paradigm. The generalization of such approaches has opened new research areas to deepen our current understanding of many physiological processes, as well as foods and nutrient functionalities in target populations. It is envisioned that this will provide new avenues toward preventive medicine and prognostic strategies for tailored therapeutic and personalized nutrition management. The development of systems biology approaches and the new generation of biomarker patterns will provide the opportunity to associate complex metabolic regulations with the etiology of multifactorial pediatric diseases. This may subsequently lead to the development of system mechanistic hypotheses that could be targeted with new nutritional personalized concepts. Therefore, this review aims to describe recent applications of metabolomics in preclinical and clinical fields with insights into disease diagnostics/monitoring and improvement of homeostasis metabolic regulation that may be translatable to novel therapeutic and nutrition advances in pediatric research.

Objective: A new tool to quantify visceral adipose tissue (VAT) over the android region of a total body dual-energy x-ray absorptiometry (DXA) scan has recently been reported. The measurement, CoreScan, is currently available on Lunar iDXA densitometers. The purpose of the study was to determine the precision of the CoreScan VAT measurement, which is critical for understanding the utility of this measure in longitudinal trials. Design and Methods: VAT precision was characterized in both an anthropomorphic imaging phantom (measured on 10 Lunar iDXA systems) and a clinical population consisting of obese women (n = 32). Results: The intrascanner precision for the VAT phantom across 9 quantities of VAT mass (0–1,800 g) ranged from 28.4 to 38.0 g. The interscanner precision ranged from 24.7 to 38.4 g. There was no statistical dependence on the quantity of VAT for either the inter- or intrascanner precision result (p = 0.670). Combining inter- and intrascanner precision yielded a total phantom precision estimate of 47.6 g for VAT mass, which corresponds to a 4.8% coefficient of variance (CV) for a 1 kg VAT mass. Our clinical population, who completed replicate total body scans with repositioning between scans, showed a precision of 56.8 g on an average VAT mass of 1110.4 g. This corresponds to a 5.1% CV. Hence, the in vivo precision result was similar to the phantom precision result. Conclusions: The study suggests that CoreScan has a relatively low precision error in both phantoms and obese women and therefore may be a useful addition to clinical trials where interventions are targeted towards changes in visceral adiposity.

The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic 1H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female’s centenarian, elderly, and young individuals. Within increasing age targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype.We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians’ unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristics of their extreme aging phenotype. Our data in centenarians support promotion of a cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP) enzyme activity. Such effective mechanism might results in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE, and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG) and p-cresol sulfate (PCS) in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.

Systems biology approaches are providing novel insights into the role of nutrition for the management of health and disease. In the present study, we investigated if dietary preference for dark chocolate in healthy subjects may lead to different metabolic response to daily chocolate consumption. Using NMR- and MS-based metabolic profiling of blood plasma and urine, we monitored the metabolic response of 10 participants stratified as chocolate desiring and eating regularly dark chocolate (CD) and 10 participants stratified as chocolate indifferent and eating rarely dark chocolate (CI) to a daily consumption of 50 g of dark chocolate as part of a standardized diet over a one week period. We demonstrated that preference for chocolate leads to different metabolic response to chocolate consumption. Daily intake of dark chocolate significantly increased HDL cholesterol by 6% and decreased polyunsaturated acyl ether phospholipids. Dark chocolate intake could also induce an improvement in the metabolism of long chain fatty acid, as noted by a compositional change in plasma fatty acyl carnitines. Moreover, a relationship between regular long-term dietary exposure to a small amount of dark chocolate, gut microbiota, and phenolics was highlighted, providing novel insights into biological processes associated with cocoa bioactives.

The discovery of biomarkers able to predict biological age of individuals is a crucial goal in aging research. Recently, researchers' attention has turn toward epigenetic markers of aging. Using the Illumina Infinium HumanMethylation450 BeadChip on whole blood DNA from a small cohort of 64 subjects of different ages, we identified 3 regions, the CpG islands of ELOVL2, FHL2, and PENK genes, whose methylation level strongly correlates with age. These results were confirmed by the Sequenom's EpiTYPER assay on a larger cohort of 501 subjects from 9 to 99 years, including 7 cord blood samples. Among the 3 genes, ELOVL2 shows a progressive increase in methylation that begins since the very first stage of life (Spearman's correlation coefficient = 0.92) and appears to be a very promising biomarker of aging.

A two by two experimental study has been designed to determine the effect of gut microbiota on energy metabolism in mouse models. The metabolic phenotype of germ-free (GF, n = 20) and conventional (n = 20) mice was characterized using a NMR spectroscopy-based metabolic profiling approach, with a focus on sexual dimorphism (20 males, 20 females) and energy metabolism in urine, plasma, liver, and brown adipose tissue (BAT). Physiological data of age-matched GF and conventional mice showed that male animals had a higher weight than females in both groups. In addition, conventional males had a significantly higher total body fat content (TBFC) compared to conventional females, whereas this sexual dimorphism disappeared in GF animals (i.e., male GF mice had a TBFC similar to those of conventional and GF females). Profiling of BAT hydrophilic extracts revealed that sexual dimorphism in normal mice was absent in GF animals, which also displayed lower BAT lactate levels and higher levels of (D)-3-hydroxybutyrate in liver, plasma, and BAT, together with lower circulating levels of VLDL. These data indicate that the gut microbiota modulate the lipid metabolism in BAT, as the absence of gut microbiota stimulated both hepatic and BAT lipolysis while inhibiting lipogenesis. We also demonstrated that (1)H NMR metabolic profiles of BAT were excellent predictors of BW and TBFC, indicating the potential of BAT to fight against obesity.

Dual-energy X-ray absorptiometry (DXA) is a well-accepted technique for measuring body composition. Knowledge of measurement precision is critical for monitoring of changes in bone mineral content (BMC), and fat and lean masses. The purpose of this study was to characterize in vivo precision of total body and regional body composition parameters using the GE Lunar iDXA (GE Healthcare Lunar, Madison, WI) system in a sample of nonobese subjects. We also evaluated the difference between expert and automatic region-of-interest (ROI) analysis on body composition precision. To this end, 2 total body scans were performed on each subject with repositioning between scans. Total body precision for BMC, fat and lean mass were 0.5%, 1.0%, and 0.5% coefficient of variation (CV), respectively. Regional body composition precision error was less than 2.5% CV for all regions except arms. Precision error was higher for the arms (CV: BMC 1.5%; fat mass 2.8%; lean mass 1.6%), likely owing to the placement of arms relative to torso leading to differences in ROI. There was a significant correlation between auto ROI and expert ROI ( r >0.99). Small, but statistically significant differences were found between auto and manual ROI. Differences were small in total body, leg, trunk, and android and gynoid regions (0.004–2.8%), but larger in arm region (3.0–6.3%). Total body and regional precision for iDXA are small and it is suggested that iDXA may be useful for monitoring changes in body composition during longitudinal trials.

This study reports a liquid chromatography-mass spectrometry method for the detection of polyphenol-derived metabolites in human plasma without enzymatic treatment after coffee consumption. Separation of available standards was achieved by reversed-phase ultra performance liquid chromatography and detection was performed by high resolution mass spectrometry in negative electrospray ionization mode. This analytical method was then applied for the identification and relative quantification of circulating coffee metabolites. A total of 34 coffee metabolites (mainly reduced, sulfated and methylated forms of caffeic acid, coumaric acid, caffeoylquinic acid and caffeoylquinic acid lactone) were identified based on mass accuracy (

The gut microbiota enhances the host’s metabolic capacity for processing nutrients and drugs and modulate the activities of multiple pathways in a variety of organ systems. We have probed the systemic metabolic adaptation to gut colonization for 20 days following exposure of axenic mice (n = 35) to a typical environmental microbial background using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy to analyze urine, plasma, liver, kidney, and colon (5 time points) metabolic profiles. Acquisition of the gut microbiota was associated with rapid increase in body weight (4%) over the first 5 days of colonization with parallel changes in multiple pathways in all compartments analyzed. The colonization process stimulated glycogenesis in the liver prior to triggering increases in hepatic triglyceride synthesis. These changes were associated with modifications of hepatic Cyp8b1 expression and the subsequent alteration of bile acid metabolites, including taurocholate and tauromuricholate, which are essential regulators of lipid absorption. Expression and activity of major drug-metabolizing enzymes (Cyp3a11 and Cyp2c29) were also significantly stimulated. Remarkably, statistical modeling of the interactions between hepatic metabolic profiles and microbial composition analyzed by 16S rRNA gene pyrosequencing revealed strong associations of the Coriobacteriaceae family with both the hepatic triglyceride, glucose, and glycogen levels and the metabolism of xenobiotics. These data demonstrate the importance of microbial activity in metabolic phenotype development, indicating that microbiota manipulation is a useful tool for beneficially modulating xenobiotic metabolism and pharmacokinetics in personalized health care., IMPORTANCE Gut bacteria have been associated with various essential biological functions in humans such as energy harvest and regulation of blood pressure. Furthermore, gut microbial colonization occurs after birth in parallel with other critical processes such as immune and cognitive development. Thus, it is essential to understand the bidirectional interaction between the host metabolism and its symbionts. Here, we describe the first evidence of an in vivo association between a family of bacteria and hepatic lipid metabolism. These results provide new insights into the fundamental mechanisms that regulate host-gut microbiota interactions and are thus of wide interest to microbiological, nutrition, metabolic, systems biology, and pharmaceutical research communities. This work will also contribute to developing novel strategies in the alteration of host-gut microbiota relationships which can in turn beneficially modulate the host metabolism.

A major source of intestinal metabolites results from both host and microbial processing of dietary nutrients. (1)H NMR-based metabolic profiling of mouse feces was carried out over time in different microbiome mouse models, including conventional (n = 9), conventionalized (n = 10), and "humanized" gnotobiotic mice inoculated with a model of human baby microbiota (HBM, n = 17). HBM mice were supplemented with Lactobacillus paracasei with (n = 10) and without (n = 7) prebiotics. Animals not supplemented with prebiotics received a diet enriched in glucose and lactose as placebo. In conventionalized animals, microbial populations and activities converged in term of multivariate mapping toward conventional mice. Both groups decreased bacterial processing of dietary proteins when switching to a diet enriched in glucose and lactose, as described with low levels of 5-aminovalerate, acetate, and propionate and high levels of lysine and arginine. The HBM model differs from conventional and conventionalized microbiota in terms of type, proportion, and metabolic activity of gut bacteria (lower short chain fatty acids (SCFAs), lactate, 5-aminovalerate, and oligosaccharides, higher bile acids and choline). The probiotics supplementation of HBM mice was associated with a specific amino acid pattern that can be linked to L. paracasei proteolytic activities. The combination of L. paracasei with the galactosyl-oligosaccharide prebiotics was related to the enhanced growth of bifidobacteria and lactobacilli, and a specific metabolism of carbohydrates, proteins, and SCFAs. The present study describes how the assessment of metabolic changes in feces may provide information for studying nutrient-microbiota relationships in different microbiome mouse models.

Chlorogenic acids (CGA) are antioxidants found in coffee. They are becoming of interest for their health-promoting effects, but bioavailability in humans is not well understood. We hypothesized that adding whole milk or sugar and nondairy creamer to instant coffee might modulate the bioavailability of coffee phenolics. Nine healthy participants were asked to randomly drink, in a crossover design, instant coffee (Coffee); instant coffee and 10% whole milk (Milk); or instant coffee, sugar, and nondairy creamer already premixed (Sugar/NDC). All 3 treatments provided the same amount of total CGA (332 mg). Blood was collected for 12 h after ingestion and plasma samples treated using a liquid-liquid extraction method that included a full enzymatic cleavage to hydrolyze all CGA and conjugates into phenolic acid equivalents. Hence, we focused our liquid chromatography-Electrospray ionization-tandem MS detection and quantification on caffeic acid (CA), ferulic acid (FA), and isoferulic acid (iFA) equivalents. Compared with a regular black instant coffee, the addition of milk did not significantly alter the area under the curve (AUC), maximum plasma concentration (C(max)), or the time needed to reach C(max) (T(max)). The C(max) of CA and iFA were significantly lower and the T(max) of FA and iFA significantly longer for the Sugar/NDC group than for the Coffee group. However, the AUC did not significantly differ. As a conclusion, adding whole milk did not alter the overall bioavailability of coffee phenolic acids, whereas sugar and nondairy creamer affected the T(max) and C(max) but not the appearance of coffee phenolics in plasma.

Gut microbiome–host metabolic interactions affect human health and can be modified by probiotic and prebiotic supplementation. Here, we have assessed the effects of consumption of a combination of probiotics (Lactobacillus paracasei or L. rhamnosus) and two galactosyl-oligosaccharide prebiotics on the symbiotic microbiome–mammalian supersystem using integrative metabolic profiling and modeling of multiple compartments in germ-free mice inoculated with a model of human baby microbiota. We have shown specific impacts of two prebiotics on the microbial populations of HBM mice when co-administered with two probiotics. We observed an increase in the populations of Bifidobacterium longum and B. breve, and a reduction in Clostridium perfringens, which were more marked when combining prebiotics with L. rhamnosus. In turn, these microbial effects were associated with modulation of a range of host metabolic pathways observed via changes in lipid profiles, gluconeogenesis, and amino-acid and methylamine metabolism associated to fermentation of carbohydrates by different bacterial strains. These results provide evidence for the potential use of prebiotics for beneficially modifying the gut microbial balance as well as host energy and lipid homeostasis.

The transgenomic metabolic effects of exposure to either Lactobacillus paracasei or Lactobacillus rhamnosus probiotics have been measured and mapped in humanized extended genome mice (germ-free mice colonized with human baby flora). Statistical analysis of the compartmental fluctuations in diverse metabolic compartments, including biofluids, tissue and cecal short-chain fatty acids (SCFAs) in relation to microbial population modulation generated a novel top-down systems biology view of the host response to probiotic intervention. Probiotic exposure exerted microbiome modification and resulted in altered hepatic lipid metabolism coupled with lowered plasma lipoprotein levels and apparent stimulated glycolysis. Probiotic treatments also altered a diverse range of pathways outcomes, including amino-acid metabolism, methylamines and SCFAs. The novel application of hierarchical-principal component analysis allowed visualization of multicompartmental transgenomic metabolic interactions that could also be resolved at the compartment and pathway level. These integrated system investigations demonstrate the potential of metabolic profiling as a top-down systems biology driver for investigating the mechanistic basis of probiotic action and the therapeutic surveillance of the gut microbial activity related to dietary supplementation of probiotics.

Irritable bowel syndrome (IBS), a highly prevalent disorder among women, has been associated with life stress, but the peripheral mechanisms involved remain largely unexplored.A 20-cm jejunal segment perfusion was performed in 2 groups of young healthy women, equilibrated by menstrual phase, experiencing either low (LS; n = 13) or moderate background stress (MS; n = 11). Intestinal effluents were collected every 15 minutes, for 30 minutes under basal conditions, and for 1 hour after cold pain stress. Cardiovascular and psychological response, changes in circulating stress and gonadal hormones, and epithelial function (net water flux, albumin output and luminal release of tryptase and alpha-defensins) to cold stress were determined.Cold pain induced a psychological response stronger in the MS than in the LS group, but similar increases in heart rate, blood pressure, adrenocorticotrophic hormone, and cortisol, whereas estradiol and progesterone remained unaltered. Notably, the jejunal epithelium of MS females showed a chloride-related decrease in peak secretory response (Delta[15-0 minutes]: LS, 97.5 [68.4-135.0]; MS, 48.8 [36.6-65.0] microL/min/cm; P.001) combined with a marked enhancement of albumin permeability (LS(AUC), 6.35 [0.9-9.6]; MS(AUC), 13.97 [8.3-23.1] mg/60 min; P = .008) after cold stress. Epithelial response in both groups was associated with similar increases in luminal tryptase and alpha-defensins release.Increased exposure to life events determines a defective jejunal epithelial response to incoming stimuli. This abnormal response may represent an initial step in the development of prolonged mucosal dysfunction, a finding that could be linked to enhanced susceptibility for IBS.

Metabolomic analysis provides biochemical profiles of low-molecular-weight endogenous metabolites in biological fluids.The aim of this study was to assess the feasibility of nuclear magnetic resonance (NMR)-based metabolomic analysis applied to exhaled breath condensate ("breathomics"). Information coming from NMR spectra was analyzed with a view to establish the NMR variables that best discriminate between children with asthma and healthy children.Twenty-five children with asthma (17 with persistent asthma treated with inhaled corticosteroids, 8 with intermittent asthma inhaled corticosteroid naive; age, 7-15 yr) and 11 healthy age-matched control subjects were enrolled. Every child performed exhaled nitric oxide measurement, spirometry, and condensate collection. Condensate samples were analyzed by means of NMR spectroscopy. Linear and partial least squares discriminant analyses were applied to data obtained from the NMR spectra.The combination of exhaled nitric oxide and FEV(1) discriminates children with asthma and healthy children with a success rate of approximately 81%, whereas selected signals from NMR spectra offer a slightly better discrimination (approximately 86%). The selected NMR variables derive from the region of 3.2 to 3.4 ppm, indicative of oxidized compounds, and from the region of 1.7 to 2.2 ppm, indicative of acetylated compounds.Metabolomics can be applied to exhaled breath condensate, leading to the characterization of airway biochemical fingerprints. The presence of acetylated compounds suggests new metabolic pathways that may have a role in asthma pathophysiology.

We here describe the development, validation and application of a quantitative methodology for the simultaneous determination of 29 elements in human serum using state-of-the-art inductively coupled plasma triple quadrupole mass spectrometry (ICP-MS/MS). This new methodology offers high-throughput elemental profiling using simple dilution of minimal quantity of serum samples. We report the outcomes of the validation procedure including limits of detection/quantification, linearity of calibration curves, precision, recovery and measurement uncertainty. ICP-MS/MS-based ionomics was used to analyze human serum of 120 older adults. Following a metabolomic data mining approach, the generated ionome profiles were subjected to principal component analysis revealing gender and age-specific differences. The ionome of female individuals was marked by higher levels of calcium, phosphorus, copper and copper to zinc ratio, while iron concentration was lower with respect to male subjects. Age was associated with lower concentrations of zinc. These findings were complemented with additional readouts to interpret micronutrient status including ceruloplasmin, ferritin and inorganic phosphate. Our data supports a gender-specific compartmentalization of the ionome that may reflect different bone remodelling in female individuals. Our ICP-MS/MS methodology enriches the panel of validated "Omics" approaches to study molecular relationships between the exposome and the ionome in relation with nutrition and health.

Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2)) under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.