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Metabolomics in Nutrition and Human Health

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 53077

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Special Issue Editors

Dr. Sergio Polakof

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Guest Editor

INRA Human Nutrition Unit, Clermont-Ferrand, France
Interests: nutrition; metabolism; nutrimetabolomics; metabolic diseases; physiology

Dr. Mireia Urpi-Sarda

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Guest Editor

Department of Nutrition, Food Science and Gastronomy, INSA-UB, XIA, Faculty of Pharmacy and Food Sciences, Food and Nutrition Torribera Campus, University of Barcelona, Av. Prat de la Riba, 171, E-08921 Santa Coloma de Gramenet, Barcelona, Spain
Interests: nutrimetabolomics; biomarkers; food metabolome databases; food metabolome; metabotypes; Mediterranean diet; dietary patterns; intervariability; cardiovascular diseases; age-related diseases; intestinal microbiota
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Special Issue Information

Dear Colleagues,

Metabolomics can be defined as the global analysis of all low molecular weight compounds in a biological sample, for example, biofluids (blood, urine, saliva, bile or cerebrospinal fluid), cellular extracts or tissues. These small molecules (<1500 Da) are the result of normal metabolism but can also be produced under the influence of external stimuli, such as dietary interventions, environmental factors or drugs.

The integration of metabolomics with nutritional science enhances current clinical and research practices by providing a deeper insight into the relationships between various metabolites and health status. In recent years, metabolomics has been used to assess nutritional status and facilitate the discovery of new biomarkers associated with specific nutrients (food metabolome) or forms of metabolic dysfunction.

Nutritional metabolomics provides better and more individualized biomarkers than most other techniques and is expected to give better indicators of the dietary effects on a target population or patients. Metabolomics has enabled the evolution of clinical research from a rather reductionist approach towards an integrative strategy. It has also provided a new way to analyse the effects of diet from genes to metabolites, giving unique insights into mechanisms underlying the development of chronic metabolic diseases, leading to comprehensive phenotyping and metabotyping of individuals on precise nutrition parameters and determining biomarkers for the early diagnosis of risk (screening biomarkers). Other biomarkers can also assist in the care of patients with suspected disease (diagnosis biomarkers) or with progression or remission of disease (prognostic biomarkers).

The purpose of this Special Issue is to expand and add to the research on the importance of metabolomic study related to human nutrition and nutrition-related disorders (obesity, metabolic syndrome, insulin resistance). Submissions may include studies focused on nutritional metabolomics aimed at investigating perturbations of the metabolome by specific diets, dietary patterns, foods, nutrients, microorganisms, or bioactive compounds and research into biomarkers linked to such perturbations. This issue welcomes the submission of manuscripts describing related original research or reviews of the scientific literature in humans (interventional, observational, cohort studies) or animal models.

Dr. Sergio Polakof
Dr. Mireia Urpi-Sarda
Guest Editors

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Keywords

metabolomics
nutrition
food
dietary-related diseases
food metabolome
animal models
biomarkers
microbiota
metabotyping

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Published Papers (10 papers)

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Research

11 pages, 546 KiB

Open AccessArticle

Effect of Korean Red Ginseng on Cholesterol Metabolites in Postmenopausal Women with Hypercholesterolemia: A Pilot Randomized Controlled Trial

by Yu-Jin Kwon, Su-Nyeong Jang, Kwang-Hyeon Liu and Dong-Hyuk Jung

Nutrients 2020, 12(11), 3423; https://doi.org/10.3390/nu12113423 - 8 Nov 2020

Cited by 16 | Viewed by 4024

Abstract

Korean red ginseng (KRG) is known to exert beneficial effects on cardiovascular health. Meanwhile, reduced estrogen at menopause has been shown to have various adverse impacts on cardiovascular risk factors, including blood lipids. The aim of this pilot study was to investigate the effect of KRG on cholesterol metabolites, which are surrogate markers of cholesterol absorption and biosynthesis, in postmenopausal women with hypercholesterolemia. The present study is an exploratory study which used data from a 4-week, double-blinded, placebo-controlled clinical pilot study in 68 postmenopausal women with hypercholesterolemia. Patients received KRG (2 g) or placebo (2 g) once daily. The primary endpoints were changes in the levels of nine sterols. Serum sterols were analyzed using liquid chromatography-mass spectrometry (LC-MS)/MS analysis. Among the sterols, reduction in cholesterol level were significantly larger in the KRG group than in the placebo group (the changes: −148.3 ± 261.1 nmol/mL in the ginseng group vs. −23.0 ± 220.5 nmol/mL in the placebo group, p = 0.039). Additionally, changes in 7-hydroxycholesterol (7-OHC) were significantly larger in the KRG group than in the placebo group (the changes: −0.05 ± 0.09 nmol/mL in the ginseng group vs. −0.002 ± 0.1 nmol/mL in the placebo group, p = 0.047). Oxysterols, cholesterol derivates, have been known to play a role in chronic inflammation diseases such as cardiovascular diseases. KRG improves sterol metabolism by decreasing cholesterol and 7-OHC levels in postmenopausal women with hypercholesterolemia. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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26 pages, 3934 KiB

Open AccessArticle

Anti-Inflammatory Potential of Cow, Donkey and Goat Milk Extracellular Vesicles as Revealed by Metabolomic Profile

by Samanta Mecocci, Federica Gevi, Daniele Pietrucci, Luca Cavinato, Francesco R. Luly, Luisa Pascucci, Stefano Petrini, Fiorentina Ascenzioni, Lello Zolla, Giovanni Chillemi and Katia Cappelli

Nutrients 2020, 12(10), 2908; https://doi.org/10.3390/nu12102908 - 23 Sep 2020

Cited by 24 | Viewed by 5170

Abstract

In recent years, extracellular vesicles (EVs), cell-derived micro and nano-sized structures enclosed in a double-layer membrane, have been in the spotlight for their high potential in diagnostic and therapeutic applications. Indeed, they act as signal mediators between cells and/or tissues through different mechanisms involving their complex cargo and exert a number of biological effects depending upon EVs subtype and cell source. Being produced by almost all cell types, they are found in every biological fluid including milk. Milk EVs (MEVs) can enter the intestinal cells by endocytosis and protect their labile cargos against harsh conditions in the intestinal tract. In this study, we performed a metabolomic analysis of MEVs, from three different species (i.e., bovine, goat and donkey) by mass spectroscopy (MS) coupled with Ultrahigh-performance liquid chromatography (UHPLC). Metabolites, both common or specific of a species, were identified and enriched metabolic pathways were investigated, with the final aim to evaluate their anti-inflammatory and immunomodulatory properties in view of prospective applications as a nutraceutical in inflammatory conditions. In particular, metabolites transported by MEVs are involved in common pathways among the three species. These metabolites, such as arginine, asparagine, glutathione and lysine, show immunomodulating effects. Moreover, MEVs in goat milk showed a greater number of enriched metabolic pathways as compared to the other kinds of milk. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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17 pages, 3389 KiB

Open AccessArticle

Urine Untargeted Metabolomic Profiling Is Associated with the Dietary Pattern of Successful Aging among Malaysian Elderly

by Nik Nur Izzati Nik Mohd Fakhruddin, Suzana Shahar, Intan Safinar Ismail, Amalina Ahmad Azam and Nor Fadilah Rajab

Nutrients 2020, 12(10), 2900; https://doi.org/10.3390/nu12102900 - 23 Sep 2020

Cited by 8 | Viewed by 3367

Abstract

Food intake biomarkers (FIBs) can reflect the intake of specific foods or dietary patterns (DP). DP for successful aging (SA) has been widely studied. However, the relationship between SA and DP characterized by FIBs still needs further exploration as the candidate markers are scarce. Thus, 1H-nuclear magnetic resonance (¹H-NMR)-based urine metabolomics profiling was conducted to identify potential metabolites which can act as specific markers representing DP for SA. Urine sample of nine subjects from each three aging groups, SA, usual aging (UA), and mild cognitive impairment (MCI), were analyzed using the ¹H-NMR metabolomic approach. Principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were applied. The association between SA urinary metabolites and its DP was assessed using the Pearson’s correlation analysis. The urine of SA subjects was characterized by the greater excretion of citrate, taurine, hypotaurine, serotonin, and melatonin as compared to UA and MCI. These urinary metabolites were associated with alteration in “taurine and hypotaurine metabolism” and “tryptophan metabolism” in SA elderly. Urinary serotonin (r = 0.48, p < 0.05) and melatonin (r = 0.47, p < 0.05) were associated with oat intake. These findings demonstrate that a metabolomic approach may be useful for correlating DP with SA urinary metabolites and for further understanding of SA development. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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20 pages, 760 KiB

Open AccessArticle

Intermittent Fasting Enhanced the Cognitive Function in Older Adults with Mild Cognitive Impairment by Inducing Biochemical and Metabolic changes: A 3-Year Progressive Study

by Theng Choon Ooi, Asheila Meramat, Nor Fadilah Rajab, Suzana Shahar, Intan Safinar Ismail, Amalina Ahmad Azam and Razinah Sharif

Nutrients 2020, 12(9), 2644; https://doi.org/10.3390/nu12092644 - 30 Aug 2020

Cited by 63 | Viewed by 15378

Abstract

Intermittent fasting (IF) refers to various dietary regimens that cycle between a period of non-fasting and a period of total fasting. This study aimed to determine the effects of IF on cognitive function among elderly individuals who practice IF who have mild cognitive impairment (MCI). A total of 99 elderly subjects with MCI of Malay ethnicity without any terminal illness were recruited from a larger cohort study, LRGS TUA. The subjects were divided into three groups, comprising those who were regularly practicing IF (r-IF), irregularly practicing IF (i-IF), and non-fasters (n-IF). Upon 36 months of follow-up, more MCI subjects in the r-IF group reverted to successful aging with no cognitive impairment and diseases (24.3%) compared to those in i-IF (14.2%) and n-IF groups (3.7%). The r-IF group’s subjects exhibited significant increment in superoxide dismutase (SOD) activity and reduction in body weight, levels of insulin, fasting blood glucose, malondialdehyde (MDA), C-reactive protein (CRP), and DNA damage. Moreover, metabolomics analysis showed that IF may modulate cognitive function via various metabolite pathways, including the synthesis and degradation of ketone bodies, butanoate metabolism, pyruvate metabolism, and glycolysis and gluconeogenesis pathways. Overall, the MCI-afflicted older adults who practiced IF regularly had better cognitive scores and reverted to better cognitive function at 36 months follow-up. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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24 pages, 3194 KiB

Open AccessArticle

Postprandial NMR-Based Metabolic Exchanges Reflect Impaired Phenotypic Flexibility across Splanchnic Organs in the Obese Yucatan Mini-Pig

by Marie Tremblay-Franco, Nathalie Poupin, Aurélien Amiel, Cécile Canlet, Didier Rémond, Laurent Debrauwer, Dominique Dardevet, Fabien Jourdan, Isabelle Savary-Auzeloux and Sergio Polakof

Nutrients 2020, 12(8), 2442; https://doi.org/10.3390/nu12082442 - 14 Aug 2020

Cited by 3 | Viewed by 3686

Abstract

The postprandial period represents one of the most challenging phenomena in whole-body metabolism, and it can be used as a unique window to evaluate the phenotypic flexibility of an individual in response to a given meal, which can be done by measuring the resilience of the metabolome. However, this exploration of the metabolism has never been applied to the arteriovenous (AV) exploration of organs metabolism. Here, we applied an AV metabolomics strategy to evaluate the postprandial flexibility across the liver and the intestine of mini-pigs subjected to a high fat–high sucrose (HFHS) diet for 2 months. We identified for the first time a postprandial signature associated to the insulin resistance and obesity outcomes, and we showed that the splanchnic postprandial metabolome was considerably affected by the meal and the obesity condition. Most of the changes induced by obesity were observed in the exchanges across the liver, where the metabolism was reorganized to maintain whole body glucose homeostasis by routing glucose formed de novo from a large variety of substrates into glycogen. Furthermore, metabolites related to lipid handling and energy metabolism showed a blunted postprandial response in the obese animals across organs. Finally, some of our results reflect a loss of flexibility in response to the HFHS meal challenge in unsuspected metabolic pathways that must be further explored as potential new events involved in early obesity and the onset of insulin resistance. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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19 pages, 2151 KiB

Open AccessArticle

Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes

by Sofiane Safi-Stibler, Etienne A. Thévenot, Luc Jouneau, Mélanie Jouin, Alexandre Seyer, Hélène Jammes, Delphine Rousseau-Ralliard, Christine Baly and Anne Gabory

Nutrients 2020, 12(6), 1572; https://doi.org/10.3390/nu12061572 - 28 May 2020

Cited by 10 | Viewed by 4030

Abstract

Nutritional changes during developmental windows are of particular concern in offspring metabolic disease. Questions are emerging concerning the role of maternal weight changes before conception, particularly for weight loss, in the development of diet-related disorders. Understanding the physiological pathways affected by the maternal trajectories in the offspring is therefore essential, but a broad overview is still lacking. We recently reported both metabolic and behavioral negative outcomes in offspring born to obese or weight-loss mothers and fed a control of high-fat diet, suggesting long-term modeling of metabolic pathways needing to be further characterized. Using non-targeted LC–HRMS, we investigated the impact of maternal and post-weaning metabolic status on the adult male offspring’s metabolome in three tissues involved in energy homeostasis: liver, hypothalamus and olfactory bulb. We showed that post-weaning diet interfered with the abundance of several metabolites, including 1,5-anhydroglucitol, saccharopine and β-hydroxybutyrate, differential in the three tissues. Moreover, maternal diet had a unique impact on the abundance of two metabolites in the liver. Particularly, anserine abundance, lowered by maternal obesity, was normalized by a preconceptional weight loss, whatever the post-weaning diet. This study is the first to identify a programming long-term effect of maternal preconception obesity on the offspring metabolome. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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21 pages, 2902 KiB

Open AccessArticle

Urinary Metabolic Profiling via LC-MS/MS Reveals Impact of Bovine Lactoferrin on Bone Formation in Growing SD Rats

by Yan Xu, Tianyu Zhao, Haowei Ren, Yindan Xie, Jingjing An, Jiaqi Shang, Dina Tabys and Ning Liu

Nutrients 2020, 12(4), 1116; https://doi.org/10.3390/nu12041116 - 17 Apr 2020

Cited by 9 | Viewed by 3839

Abstract

Lactoferrin (LF) exerts a promoting bone health function. The effects of LF on bone formation at the metabolic level have been less explored. Urinary metabolic profiling of growing Sprague-Dawley (SD) rats LF-supplemented (1000 mg/kg bw) for four weeks were explored by Liquid chromatography–tandem mass spectrometry (LC-MS/MS). The serum markers of bone formation and bone resorption, the bone mass, and the osteogenesis markers of femur were measured by an enzyme-linked immunosorbent assay, micro-computerized tomography, and immunohistochemistry, respectively. Compared with the control, LF supplementation improved bone formation (p < 0.05), reduced bone resorption (p < 0.05), enhanced femoral bone mineral density and microarchitecture (p < 0.05), and upregulated osteocalcin, osterix, and Runx-2 expression (p < 0.05) of femur. LF upregulated 69 urinary metabolites. KEGG and pathway enrichment analyses of those urinary metabolites, and the Person’s correlation analyses among those urinary metabolites and bone status revealed that LF impacted on bone formation via regulatory comprehensive pathways including taurine and hypotaurine metabolism, arginine and proline metabolism, cyanoamino acid metabolism, nitrogen metabolism, nicotinate and nicotinamide metabolism, and fatty acid biosynthesis. The present study indicated the metabolomics is a useful and practical tool to elucidate the mechanisms by which LF augments bone mass formation in growing animals. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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19 pages, 2637 KiB

Open AccessArticle

Feeding the Outer Bran Fraction of Rice Alters Hepatic Carbohydrate Metabolism in Rats

by Mana Kawaguchi, Nao Nishikoba, Saki Shimamoto, Shozo Tomonaga, Rukana Kohrogi, Yoko Yamauchi, Yoshikazu Fujita, Akira Ohtsuka and Daichi Ijiri

Nutrients 2020, 12(2), 430; https://doi.org/10.3390/nu12020430 - 7 Feb 2020

Cited by 1 | Viewed by 3039

Abstract

Dietary intake of fiber-rich food has been reported to contribute to multiple health benefits. The aim of the current study is to investigate the effects of a diet containing the outer bran fraction of rice (OBFR), which is rich in insoluble fiber, on the intestinal environment and metabolite profiles of rats. Fourteen 8-week-old male Sprague–Dawley rats were divided into a control group and an OBFR group. For a period of 21 days, the control group was fed a control diet, while the OBFR group was fed a diet containing 5% OBFR. Metabolomics analysis revealed drastic changes in the cecal metabolites of the rats fed the OBFR diet. Furthermore, in the plasma and liver tissue, the concentrations of metabolites involved in pyruvate metabolism, the pentose phosphate pathway, gluconeogenesis, or valine, leucine, isoleucine degradation were changed. Concordantly, the OBFR diet increased the expression of genes encoding enzymes involved in these metabolic pathways in the livers of the rats. Collectively, these results suggest that the OBFR diet altered the concentrations of metabolites in the cecal contents, plasma, and liver, and the hepatic gene expressions of rats, and that this may have mainly contributed to carbohydrate metabolism in the liver. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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20 pages, 1854 KiB

Open AccessArticle

Beneficial Effects of a Low-dose of Conjugated Linoleic Acid on Body Weight Gain and other Cardiometabolic Risk Factors in Cafeteria Diet-fed Rats

by Miguel Z Martín-González, Héctor Palacios, Miguel A Rodríguez, Lluís Arola, Gerard Aragonès and Begoña Muguerza

Nutrients 2020, 12(2), 408; https://doi.org/10.3390/nu12020408 - 4 Feb 2020

Cited by 11 | Viewed by 4436

Abstract

Conjugated linoleic acid (CLA) is a dietary supplement that has been shown to improve obesity. However, some authors have associated high doses of CLA supplementation with liver impairment and insulin resistance. The aim of this study was to assess whether the consumption of low doses of CLA maintained the beneficial effects on the main metabolic disturbances associated with metabolic syndrome (MetS) but prevented the occurrence of non-desirable outcomes associated with its consumption. Male Wistar rats, fed standard or cafeteria (CAF) diet for 12 weeks, were supplemented with three different low doses of CLA in the last three weeks. Both biochemical and H¹ NMR-based metabolomics profiles were analysed in serum and liver. The consumption of 100 mg/kg CLA, but not doses of 200 and 300 mg/kg, ameliorated the increase in body weight gain as well as the serum concentrations of glucose, insulin, cholesterol, triglyceride, diglyceride, and total phospholipid induced by a CAF diet. In turn, CLA reverted the increase in lactate, alanine, and glucose concentrations in the liver of these animals, but enhanced hepatic cholesterol accumulation without any detrimental effect on liver function. In conclusion, a low dose of CLA corrected the adverse effects associated with MetS without compromising other metabolic parameters. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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16 pages, 1742 KiB

Open AccessArticle

DHA-Induced Perturbation of Human Serum Metabolome. Role of the Food Matrix and Co-Administration of Oat β-glucan and Anthocyanins

by Veronica Ghini, Leonardo Tenori, Francesco Capozzi, Claudio Luchinat, Achim Bub, Corinne Malpuech-Brugere, Caroline Orfila, Luigi Ricciardiello and Alessandra Bordoni

Nutrients 2020, 12(1), 86; https://doi.org/10.3390/nu12010086 - 27 Dec 2019

Cited by 7 | Viewed by 3937

Abstract

Docosahexaenoic acid (DHA) has been reported to have a positive impact on many diet-related disease risks, including metabolic syndrome. Although many DHA-enriched foods have been marketed, the impact of different food matrices on the effect of DHA is unknown. As well, the possibility to enhance DHA effectiveness through the co-administration of other bioactives has seldom been considered. We evaluated DHA effects on the serum metabolome administered to volunteers at risk of metabolic syndrome as an ingredient of three different foods. Foods were enriched with DHA alone or in combination with oat beta-glucan or anthocyanins and were administered to volunteers for 4 weeks. Serum samples collected at the beginning and end of the trial were analysed by NMR-based metabolomics. Multivariate and univariate statistical analyses were used to characterize modifications in the serum metabolome and to evaluate bioactive-bioactive and bioactive-food matrix interactions. DHA administration induces metabolome perturbation that is influenced by the food matrix and the co-presence of other bioactives. In particular, when co-administered with oat beta-glucan, DHA induces a strong rearrangement in the lipoprotein profile of the subjects. The observed modifications are consistent with clinical results and indicate that metabolomics represents a possible strategy to choose the most appropriate food matrices for bioactive enrichment. Full article

(This article belongs to the Special Issue Metabolomics in Nutrition and Human Health)

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