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Nutrition, Metabolites, and Human Health

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

Deadline for manuscript submissions: closed (20 April 2023) | Viewed by 92826

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Guest Editor
Institut d'Investigació Sanitària Pere Virgili, Reus, Spain
Interests: metabolomics; gut microbiota; diet; nutrition; aging; cardiometabolic diseases; cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advances in high-throughput metabolomics profiling have allowed epidemiology research to advance our understanding in many aspects of human health. Nutritional epidemiology has not been the exception, and the integration of metabolomics into traditional nutritional research has already provided new functional insight into the role of nutrition in health. Furthermore, metabolomics holds considerable promise for discovering new biomarkers of nutrient intake that may more precisely define the nutritional exposure, complementing self-report dietary assessment methods and providing better estimates of disease risk in epidemiological studies.

The purpose of this Special Issue of Nutrients, entitled “Nutrition, Metabolites, and Human Health”, is to add to the current nutritional metabolomics evidence from original research or narrative/systematic reviews of the recent scientific literature or meta-analyses in humans (interventional and observational studies) or animal models. This issue welcomes the submission of manuscripts that integrate metabolomics, and also other omics techniques, such as genomics and metagenomics, with nutrition and that examine their role in human health.

Dr. Christopher Papandreou
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolomics
  • microbial metabolites
  • gut microbiota
  • diet
  • food
  • nutrition
  • aging
  • cardiometabolic outcomes
  • cancer

Published Papers (24 papers)

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Editorial

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5 pages, 228 KiB  
Editorial
Nutrition, Metabolites, and Human Health
by Christopher Papandreou
Nutrients 2023, 15(19), 4286; https://doi.org/10.3390/nu15194286 - 08 Oct 2023
Viewed by 1212
Abstract
The field of metabolomics and related “omics” techniques allows for the identification of a vast array of molecules within biospecimens [...] Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)

Research

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15 pages, 2380 KiB  
Article
Characterisation of Fasting and Postprandial NMR Metabolites: Insights from the ZOE PREDICT 1 Study
by Kate M. Bermingham, Mohsen Mazidi, Paul W. Franks, Tyler Maher, Ana M. Valdes, Inbar Linenberg, Jonathan Wolf, George Hadjigeorgiou, Tim D. Spector, Cristina Menni, Jose M. Ordovas, Sarah E. Berry and Wendy L. Hall
Nutrients 2023, 15(11), 2638; https://doi.org/10.3390/nu15112638 - 05 Jun 2023
Cited by 4 | Viewed by 2048
Abstract
Background: Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here, we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability, following a standardised meal in the ZOE PREDICT 1 cohort. Methods: In the ZOE [...] Read more.
Background: Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here, we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability, following a standardised meal in the ZOE PREDICT 1 cohort. Methods: In the ZOE PREDICT 1 study (n = 1002 (NCT03479866)), 250 metabolites, mainly lipids, were measured by a Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over time was evaluated using linear mixed modelling and intraclass correlation coefficients (ICC) were calculated. Results: Postprandially, 85% (of 250 metabolites) significantly changed from fasting at 6 h (47% increased, 53% decreased; Kruskal–Wallis), with 37 measures increasing by >25% and 14 increasing by >50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearman’s rho >0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho <0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08–0.99). The lowest ICCs (ICC <0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies (β-hydroxybutyrate, acetoacetate, acetate) and lactate. Conclusions: In this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following sequential mixed meals. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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23 pages, 3448 KiB  
Article
In Vitro Screening for Probiotic Properties of Lactobacillus and Bifidobacterium Strains in Assays Relevant for Non-Alcoholic Fatty Liver Disease Prevention
by Silvia Lopez-Escalera, Mari L. Lund, Gerben D. A. Hermes, Béatrice S.-Y. Choi, Kei Sakamoto and Anja Wellejus
Nutrients 2023, 15(10), 2361; https://doi.org/10.3390/nu15102361 - 18 May 2023
Cited by 5 | Viewed by 2804
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that poses health challenges worldwide and is expected to continue to rise dramatically. NAFLD is associated with metabolic syndrome, type 2 diabetes mellitus, and impaired gut health. Increased gut permeability, caused by disturbance [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that poses health challenges worldwide and is expected to continue to rise dramatically. NAFLD is associated with metabolic syndrome, type 2 diabetes mellitus, and impaired gut health. Increased gut permeability, caused by disturbance of tight junction proteins, allows passage of damaging microbial components that, upon reaching the liver, have been proposed to trigger the release of inflammatory cytokines and generate cellular stress. A growing body of research has suggested the utilization of targeted probiotic supplements as a preventive therapy to improve gut barrier function and tight junctions. Furthermore, specific microbial interactions and metabolites induce the secretion of hormones such as GLP-1, resulting in beneficial effects on liver health. To increase the likelihood of finding beneficial probiotic strains, we set up a novel screening platform consisting of multiple in vitro and ex vivo assays for the screening of 42 bacterial strains. Analysis of transepithelial electrical resistance response via co-incubation of the 42 bacterial strains with human colonic cells (Caco-2) revealed improved barrier integrity. Then, strain-individual metabolome profiling was performed revealing species-specific clusters. GLP-1 secretion assay with intestinal secretin tumor cell line (STC-1) found at least seven of the strains tested capable of enhancing GLP-1 secretion in vitro. Gene expression profiling in human biopsy-derived intestinal organoids was performed using next generation sequencing transcriptomics post bacterial co-incubation. Here, different degrees of immunomodulation by the increase in certain cytokine and chemokine transcripts were found. Treatment of mouse primary hepatocytes with selected highly produced bacterial metabolites revealed that indole metabolites robustly inhibited de novo lipogenesis. Collectively, through our comprehensive bacterial screening pipeline, not previously ascribed strains from both Lactobacillus and Bifidobacterium genera were proposed as potential probiotics based on their ability to increase epithelial barrier integrity and immunity, promote GLP-1 secretion, and produce metabolites relevant to liver health. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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16 pages, 2007 KiB  
Article
Different Dietary Ratios of Camelina Oil to Sandeel Oil Influence the Capacity to Synthesise and Deposit EPA and DHA in Zucker Fa/Fa Rats
by Tone-Kari Knutsdatter Østbye, Oddrun Anita Gudbrandsen, Aslaug Drotningsvik, Bente Ruyter, Gerd Marit Berge, Gjermund Vogt and Astrid Nilsson
Nutrients 2023, 15(10), 2344; https://doi.org/10.3390/nu15102344 - 17 May 2023
Cited by 3 | Viewed by 1234
Abstract
Plant-based food provides more ALA (α-linolenic acid) and less EPA (eicosapentaenoic acid) and DHA (docosahexanoic acid) than marine food. Earlier studies indicate that cetoleic acid (22:1n-11) stimulates the n-3 pathway from ALA to EPA and DHA. The present study aimed [...] Read more.
Plant-based food provides more ALA (α-linolenic acid) and less EPA (eicosapentaenoic acid) and DHA (docosahexanoic acid) than marine food. Earlier studies indicate that cetoleic acid (22:1n-11) stimulates the n-3 pathway from ALA to EPA and DHA. The present study aimed to investigate the dietary effects of camelina oil (CA) high in ALA and sandeel oil (SA) high in cetoleic acid on the conversion of ALA to EPA and DHA. Male Zucker fa/fa rats were fed a diet of soybean oil (Ctrl) or diets of CA, SA, or a combination of CA and SA. Significantly higher levels of DPA (docosapentaenoic acid) and DHA in blood cells from the CA group compared to the Ctrl indicate an active conversion of ALA to DPA and DHA. Increasing the uptake and deposition of EPA and DHA meant that a trend towards a decrease in the liver gene expression of Elovl5, Fads1, and Fads2 along with an increase in the dietary content of SA was observed. However, 25% of the SA could be exchanged with CA without having a significant effect on EPA, DPA, or DHA in blood cells, indicating that bioactive components in SA, such as cetoleic acid, might counteract the inhibiting effect of the high dietary content of DHA on the n-3 biosynthetic pathway. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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11 pages, 1618 KiB  
Article
Impact of Maternal Lifestyle and Dietary Habits during Pregnancy on Newborn Metabolic Profile
by Ilaria Cicalini, Samanta Moffa, Maria Lucia Tommolini, Silvia Valentinuzzi, Mirco Zucchelli, Ines Bucci, Piero Chiacchiaretta, Antonella Fontana, Luca Federici, Vincenzo De Laurenzi, Piero Del Boccio, Claudia Rossi and Damiana Pieragostino
Nutrients 2023, 15(10), 2297; https://doi.org/10.3390/nu15102297 - 13 May 2023
Cited by 5 | Viewed by 1887
Abstract
Expanded newborn screening (NBS) is a preventive program that allows for the early identification of over 40 congenital endocrine-metabolic diseases by analyzing dried blood spot samples collected from the newborn’s heel within 48–72 h of birth. The determination of amino acids and acyl-carnitines [...] Read more.
Expanded newborn screening (NBS) is a preventive program that allows for the early identification of over 40 congenital endocrine-metabolic diseases by analyzing dried blood spot samples collected from the newborn’s heel within 48–72 h of birth. The determination of amino acids and acyl-carnitines by Flow Injection Analysis Tandem Mass Spectrometry (FIA-MS/MS) may also highlight metabolic alterations resulting from external factors, such as maternal nutrition. In the present study, we developed a questionnaire to investigate the eating habits of 109 women during pregnancy and statistically correlated the results from the investigation on dietary habits with the data obtained by the NBS laboratory of Abruzzo region (Italy). Parameters such as smoking, physical activity, and the intake of iodized salt, drugs, and supplements were analyzed. This study aimed to highlight how maternal lifestyle, diet, and drug intake during pregnancy may affect the neonatal metabolic profile, possibly generating false positive or false negative results in the NBS test. The results pointed out how the knowledge of maternal nutrition and lifestyle may also be precious in preventing misinterpretations of the neonatal metabolic profile, thereby reducing unnecessary stress for newborns and their parents and limiting costs for the health system. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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18 pages, 6799 KiB  
Article
Comparison of the Activity of Fecal Enzymes and Concentration of SCFA in Healthy and Overweight Children
by Katarzyna Śliżewska, Michał Włodarczyk, Martyna Sobczak, Renata Barczyńska, Janusz Kapuśniak, Piotr Socha, Aldona Wierzbicka-Rucińska and Aneta Kotowska
Nutrients 2023, 15(4), 987; https://doi.org/10.3390/nu15040987 - 16 Feb 2023
Cited by 3 | Viewed by 2264
Abstract
In modern societies obesity has become a serious issue which must be urgently addressed. The health implications of neglected obesity are substantial, as not only does it affect individuals’ everyday lives, but it also leads to significantly increased mortality due to the development [...] Read more.
In modern societies obesity has become a serious issue which must be urgently addressed. The health implications of neglected obesity are substantial, as not only does it affect individuals’ everyday lives, but it also leads to significantly increased mortality due to the development of several disorders such as type-2 diabetes, cardiovascular diseases, cancers, and depression. The objective of this research was to investigate the alterations in selected health markers caused by overweight and obesity in children. The measured parameters were the activity of the fecal enzymes, the concentration of short-chain fatty acids (SCFAs), and the concentration of branched-chain fatty acids (BCFAs). The activity of the fecal enzymes, specifically α-glucosidase, α-galactosidase, β-glucosidase, β-galactosidase, and β-glucuronidase, was determined using spectrophotometry at a wavelength of 400 nm. Furthermore, concentrations of lactic acid, SCFAs (formic, acetic, propionic, butyric, and valeric acids), and BCFAs (isobutyric and isovaleric acids) were determined using the HPLC method. The obtained results reveal that obese children have different fecal enzyme activity and a different profile of fatty acids from children of normal weight. The group of obese children, when compared to children of normal weight, had increased concentrations of BCFAs (p < 0.05) and higher activity of potentially harmful enzymes such as β-glucosidase and β-glucuronidase (p < 0.05). In comparison, children of normal weight exhibited significantly increased concentrations of lactic acid and SCFAs (especially formic and butyric acids) (p < 0.05). Furthermore, their α-glucosidase and α-galactosidase activity were higher when compared to the group of obese children (p < 0.05). These results suggest that the prevalence of obesity has a significant impact on metabolites produced in the gastrointestinal tract, which might result in a higher chance of developing serious diseases. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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15 pages, 2558 KiB  
Article
Associations of Serum 25(OH)D, PTH, and β-CTX Levels with All-Cause Mortality in Chinese Community-Dwelling Centenarians
by Bin Wang, Xiaowei Cheng, Shihui Fu, Ding Sun, Weiguang Zhang, Weicen Liu, Xinyu Miao, Qing Luo, Hao Li, Jie Zhang, Xinye Jin, Yali Zhao, Yao Yao and Yizhi Chen
Nutrients 2023, 15(1), 94; https://doi.org/10.3390/nu15010094 - 24 Dec 2022
Cited by 3 | Viewed by 2164
Abstract
This longitudinal cohort study explored the associations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), and β-C-terminal telopeptide of type 1 collagen (β-CTX) levels with all-cause mortality in centenarians. The study included 952 centenarians (81.4% female). During a median follow-up of 32 [...] Read more.
This longitudinal cohort study explored the associations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), and β-C-terminal telopeptide of type 1 collagen (β-CTX) levels with all-cause mortality in centenarians. The study included 952 centenarians (81.4% female). During a median follow-up of 32 months, 752 (78.9%) centenarians died. The estimated 1-year, 3-year, and 5-year survival rates were 80.0%, 45.7%, and 23.6%, respectively. The association of mortality with 25(OH)D was linear, whereas the associations with PTH and β-CTX were J-shaped, with a lower risk below the median levels. Compared with 25(OH)D of ≥30 ng/mL, 25(OH)D < 30 ng/mL was associated with increased mortality (HR 1.52, 95% CI 1.24–1.86, p < 0.001). Compared with PTH of ≤65 pg/mL, PTH > 65 pg/mL was associated with increased mortality (HR 1.30, 95% CI 1.08–1.56, p = 0.005). Compared with β-CTX of <0.55 ng/mL, β-CTX ≥ 0.55 ng/mL was associated with increased mortality (HR 1.30, 95% CI 1.10–1.54, p = 0.002). A higher β-CTX level (even in the clinical reference range of 0.55–1.01 ng/mL) was associated with increased mortality (HR 1.23, 95% CI 1.04–1.47, p = 0.018). Centenarians with 25(OH)D < 30 ng/mL, PTH > 65 pg/mL, and β-CTX ≥ 0.55 ng/mL had a 2.77-fold (95% CI 1.99–3.85, p < 0.001) increased risk of mortality when compared with those with 25(OH)D of >30 ng/mL, PTH < 65 pg/mL, and β-CTX < 0.55 ng/mL. Lower serum 25(OH)D and higher PTH and β-CTX were independently correlated with increased all-cause mortality in Chinese community-dwelling centenarians. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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12 pages, 1627 KiB  
Article
Biomedical Indicators of Patients with Non-Puerperal Mastitis: A Retrospective Study
by Liang Shi, Jing Wu, Yue Hu, Xu Zhang, Zhi Li, Pei-Wen Xi, Ji-Fu Wei and Qiang Ding
Nutrients 2022, 14(22), 4816; https://doi.org/10.3390/nu14224816 - 14 Nov 2022
Cited by 5 | Viewed by 1977
Abstract
Background: Non-puerperal mastitis (NPM), a recurrent chronic inflammation of non-lactating breast, often proves tremendous difficulty in treatment, and it may give rise to its complicated symptoms and unclear etiology. Furthermore, the clinical morbidity rate of NPM has been increasing in recent years. Methods: [...] Read more.
Background: Non-puerperal mastitis (NPM), a recurrent chronic inflammation of non-lactating breast, often proves tremendous difficulty in treatment, and it may give rise to its complicated symptoms and unclear etiology. Furthermore, the clinical morbidity rate of NPM has been increasing in recent years. Methods: Overall, 284 patients diagnosed with NPM were consecutively recruited as cases in this study, and patients with benign breast disease (n = 1128) were enrolled as control. The clinical, biomedical, and pathological indicators were analyzed. Univariate and multivariate logistic analysis were used to distinguish risks between NPM and benign breast mass patients. Furthermore, according to the pathological characteristics, the patients of NPM were classified into two subgroups: mammary duct ectasia (MDE) and granulomatous lobular mastitis (GLM). The differences of biomedical indicators between MDE and GLM groups were also analyzed. Results: Compared with benign breast mass group, the level of high-density lipoprotein (HDL-C) significantly decreased, while lipoprotein(a) (Lp(a)) and blood glucose (GLU) both increased in NPM group. According to univariate and multivariate logistic analysis, the onset age and HDL-C were generally decreased, while Lp(a) and GLU were increased in NPM group. The onset age, HDL-C, Lp(a), and GLU were modeled to distinguish NPM and benign breast mass. Significant differences were also observed between MDE and GLM patients in biomedical indicators, such as lipoprotein(a) (Lp(a)), lactate dehydrogenase (LDH), creatine kinase (CK), total cholesterol (TC), and so on. Conclusions: Our results indicated for the first time that biomarkers were associated with NPM. The biomedical indicators involved in lipid metabolism might be important factors in the development and treatment of NPM. In addition, MDE and GLM are two diseases with different inflammatory states of NPM. These findings would be helpful for a better understanding of NPM and give us some insights to develop new diagnostic and therapeutic strategies. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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12 pages, 3204 KiB  
Article
Effect of Tetragonia tetragonoides (Pall.) Kuntze Extract on Andropause Symptoms
by Ka Youn Lee, Seung-Hyung Kim, Won-Kyung Yang and Geung-Joo Lee
Nutrients 2022, 14(21), 4572; https://doi.org/10.3390/nu14214572 - 31 Oct 2022
Cited by 4 | Viewed by 1527
Abstract
Testosterone and free testosterone levels decrease in men as they age, consequently inducing andropause symptoms, such as weight gain, fatigue, and depression. Therefore, this study aimed to evaluate the reducing effect of New Zealand spinach (NZS) on these androgenic symptoms by orally administering [...] Read more.
Testosterone and free testosterone levels decrease in men as they age, consequently inducing andropause symptoms, such as weight gain, fatigue, and depression. Therefore, this study aimed to evaluate the reducing effect of New Zealand spinach (NZS) on these androgenic symptoms by orally administering its extract to 26-week-old rats for four weeks. Biochemical blood testing was conducted, and the andropause symptoms-related indicators and muscular endurance levels were examined. In the NZS extract-treated rats, the decrease in muscle mass was suppressed, and immobility time was reduced in the forced swim test. In addition, the grip force and muscular endurance of the forelimbs were significantly increased compared to the control group; therefore, NZS extract exhibits a positive effect on the maintenance of muscle mass and improves muscular endurance. The representative male hormones, testosterone and progesterone, in the NZS extract-treated group were 1.84 times and 2.48 times higher than those in the control groups, respectively. Moreover, cholesterol and low-density lipoprotein, which affect lipid metabolism, were significantly reduced in the NZS extract-treated group. Overall, NZS extract shows potential for further development as a functional food material for improving muscle strength and relieving andropause symptoms. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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9 pages, 8550 KiB  
Article
Mechanisms of Sodium/Iodide Symporter-Mediated Mammary Gland Iodine Compensation during Lactation
by Min Fu, Yuanpeng Gao, Wenxing Guo, Qi Meng, Qi Jin, Rui Yang, Ying Yang, Yaqi Zhang and Wanqi Zhang
Nutrients 2022, 14(17), 3592; https://doi.org/10.3390/nu14173592 - 31 Aug 2022
Cited by 2 | Viewed by 1582
Abstract
This research aimed to investigate the compensation mechanism of iodine deficiency and excess in the mammary gland during lactation. Female rats were divided into the low iodine group (LI), the normal iodine group (NI), the 10-fold high iodine group (10HI) and the 50-fold [...] Read more.
This research aimed to investigate the compensation mechanism of iodine deficiency and excess in the mammary gland during lactation. Female rats were divided into the low iodine group (LI), the normal iodine group (NI), the 10-fold high iodine group (10HI) and the 50-fold high iodine group (50HI). We measured the iodine levels in the urine, blood, milk, and mammary gland. The protein expression of sodium/iodide symporter (NIS), DPAGT1, and valosin-containing protein (VCP) in the mammary gland was also studied. The 24-hour urinary iodine concentration, serum total iodine concentration, serum non-protein-bound iodine concentration, breast milk iodine concentration, and mammary gland iodine content in the 50HI group were significantly higher than those in the NI group (p < 0.05). Compared with the NI group, NIS expression in the 50HI group significantly decreased (p < 0.05). DAPGT1 expression was significantly higher in the LI group than in the NI group (p < 0.05). The expression level of VCP was significantly increased in the 10HI and 50HI groups. In conclusion, milk iodine concentration is positively correlated with iodine intake, and the lactating mammary gland regulates the glycosylation and degradation of NIS by regulating DPAGT1 and VCP, thus regulating milk iodine level. However, the mammary gland has a limited role in compensating for iodine deficiency and excess. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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20 pages, 3254 KiB  
Article
Synergistic Effect of β-Lapachone and Aminooxyacetic Acid on Central Metabolism in Breast Cancer
by Mario C. Chang, Rohit Mahar, Marc A. McLeod, Anthony G. Giacalone, Xiumei Huang, David A. Boothman and Matthew E. Merritt
Nutrients 2022, 14(15), 3020; https://doi.org/10.3390/nu14153020 - 22 Jul 2022
Cited by 7 | Viewed by 2299
Abstract
The compound β-lapachone, a naturally derived naphthoquinone, has been utilized as a potent medicinal nutrient to improve health. Over the last twelve years, numerous reports have demonstrated distinct associations of β-lapachone and NAD(P)H: quinone oxidoreductase 1 (NQO1) protein in the amelioration of various [...] Read more.
The compound β-lapachone, a naturally derived naphthoquinone, has been utilized as a potent medicinal nutrient to improve health. Over the last twelve years, numerous reports have demonstrated distinct associations of β-lapachone and NAD(P)H: quinone oxidoreductase 1 (NQO1) protein in the amelioration of various diseases. Comprehensive research of NQO1 bioactivity has clearly confirmed the tumoricidal effects of β-lapachone action through NAD+-keresis, in which severe DNA damage from reactive oxygen species (ROS) production triggers a poly-ADP-ribose polymerase-I (PARP1) hyperactivation cascade, culminating in NAD+/ATP depletion. Here, we report a novel combination strategy with aminooxyacetic acid (AOA), an aspartate aminotransferase inhibitor that blocks the malate-aspartate shuttle (MAS) and synergistically enhances the efficacy of β-lapachone metabolic perturbation in NQO1+ breast cancer. We evaluated metabolic turnover in MDA-MB-231 NQO1+, MDA-MB-231 NQO1, MDA-MB-468, and T47D cancer cells by measuring the isotopic labeling of metabolites from a [U-13C]glucose tracer. We show that β-lapachone treatment significantly hampers lactate secretion by ~85% in NQO1+ cells. Our data demonstrate that combinatorial treatment decreases citrate, glutamate, and succinate enrichment by ~14%, ~50%, and ~65%, respectively. Differences in citrate, glutamate, and succinate fractional enrichments indicate synergistic effects on central metabolism based on the coefficient of drug interaction. Metabolic modeling suggests that increased glutamine anaplerosis is protective in the case of MAS inhibition. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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15 pages, 1025 KiB  
Article
Evaluation of a Physical Activity and Multi-Micronutrient Intervention on Cognitive and Academic Performance in South African Primary Schoolchildren
by Johanna Beckmann, Siphesihle Nqweniso, Sebastian Ludyga, Rosa du Randt, Annelie Gresse, Kurt Z. Long, Madeleine Nienaber, Harald Seelig, Uwe Pühse, Peter Steinmann, Jürg Utzinger, Cheryl Walter, Markus Gerber and Christin Lang
Nutrients 2022, 14(13), 2609; https://doi.org/10.3390/nu14132609 - 23 Jun 2022
Cited by 4 | Viewed by 2124
Abstract
Executive functions (EFs) are essential for optimal academic development. Appropriate nutrition and physical activity (PA) have been shown to facilitate optimal cognitive development. Therefore, this study examined whether a 12-week school-based PA and multi-micronutrient supplementation (MMNS) intervention would improve cognitive and academic performance. [...] Read more.
Executive functions (EFs) are essential for optimal academic development. Appropriate nutrition and physical activity (PA) have been shown to facilitate optimal cognitive development. Therefore, this study examined whether a 12-week school-based PA and multi-micronutrient supplementation (MMNS) intervention would improve cognitive and academic performance. A cluster-randomized controlled trial (RCT) was conducted. Children from four schools located in a peri-urban area of South Africa were randomly assigned to (i) PA + MMNS, (ii) PA + placebo, (iii) MMNS or (iv) placebo. Information processing and inhibitory control were measured with a computerized Flanker task. End-of-year results provided insight into academic achievement. Anthropometric measures were used to determine nutritional status. Data were analyzed with linear mixed-models, adjusting for baseline scores, school classes and age; 932 children (458 girls (49.1%), Mage (mean age) = 8.42 ± 1.94 years) completed baseline and post-intervention assessments. Cognitive performance improved among all four groups, with no significant group × time effects. For academic achievement, there was no significant interaction effect between the combined intervention group and placebo. We encourage future studies in this neglected area in order to determine the most optimal design of school-based nutrition and PA programs to enhance overall cognitive performance. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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11 pages, 280 KiB  
Article
Association between Dietary Macronutrient Intake and Symptoms in Uninvestigated Dyspepsia: Evidence from a Population-Based, Cross-Sectional Study
by Shahram Agah, Azadeh Aminianfar, Ammar Hassanzadeh Keshteli, Vida Bitarafan, Peyman Adibi, Ahmad Esmaillzadeh and Christine Feinle-Bisset
Nutrients 2022, 14(13), 2577; https://doi.org/10.3390/nu14132577 - 22 Jun 2022
Cited by 2 | Viewed by 1751
Abstract
(1) Background: Limited evidence from laboratory-based studies suggests that specific dietary macronutrients, particularly fat, can induce dyspeptic symptoms. Through a population-based study, we investigated the relationship between dietary macronutrients and dyspeptic symptoms and sought to determine macronutrient intake thresholds to predict or prevent [...] Read more.
(1) Background: Limited evidence from laboratory-based studies suggests that specific dietary macronutrients, particularly fat, can induce dyspeptic symptoms. Through a population-based study, we investigated the relationship between dietary macronutrients and dyspeptic symptoms and sought to determine macronutrient intake thresholds to predict or prevent dyspepsia and reduce symptoms in patients with dyspepsia. (2) Methods: A total of 4763 Iranian people were enrolled in this population-based, cross-sectional study. Uninvestigated dyspepsia (UD) and its symptoms, including postprandial fullness, early satiation, and epigastric pain, were evaluated using a modified Persian version of the Rome III criteria. The dietary intakes of participants were evaluated using a validated food–frequency questionnaire. Receiver operating characteristic (ROC) curve analysis was used to calculate threshold intakes of dietary macronutrients to prevent UD in the general population. The analysis was then repeated in those with UD to calculate intake thresholds for reducing UD symptoms. (3) Results: Early satiation occurred in 6.3% (n = 302), postprandial fullness in 8.0% (n = 384) and epigastric pain in 7.8% (n = 371) of participants. The prevalence of UD was 15.2%. Compared with individuals without UD, those with UD had a lower intake of carbohydrates (48.2% vs. 49.1%) and a higher intake of fats (38.3% vs. 37.4%), while protein and energy intakes did not differ. Higher dietary fat and protein intakes were associated with a higher prevalence of postprandial fullness and epigastric pain, respectively. Macronutrient intakes to predict UD in the general population were <49% of energy from carbohydrates, >14.7% from protein, and >37.7% from fats. Carbohydrate, protein, and fat intakes to prevent symptoms among those with UD were calculated to be >48.2%, <14.6%, and <38.6%, respectively. (4) Conclusion: Higher carbohydrate intake and lower fat or protein intakes were associated with a lower likelihood of UD. Prospective studies carefully manipulating dietary macronutrient composition are warranted to investigate the value of dietary changes to improve symptoms in people with UD. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
17 pages, 3632 KiB  
Article
1H NMR-Based Metabolomics Reveals the Intrinsic Interaction of Age, Plasma Signature Metabolites, and Nutrient Intake in the Longevity Population in Guangxi, China
by He Li, Minhong Ren and Quanyang Li
Nutrients 2022, 14(12), 2539; https://doi.org/10.3390/nu14122539 - 18 Jun 2022
Cited by 10 | Viewed by 2658
Abstract
Health and longevity populations have distinct metabolic and nutrient intake profiles. However, the relationship between biomarkers of longevity-related metabolites and dietary nutrient intake profiles, as well as metabolic markers associated with longevity features, have not been fully elucidated. Therefore, 1H nuclear magnetic [...] Read more.
Health and longevity populations have distinct metabolic and nutrient intake profiles. However, the relationship between biomarkers of longevity-related metabolites and dietary nutrient intake profiles, as well as metabolic markers associated with longevity features, have not been fully elucidated. Therefore, 1H nuclear magnetic resonance (1H NMR)-based plasma metabolomics profiling was conducted in the present study to identify potential metabolites which can be used as specific markers for the evaluation of healthy aging. Plasma samples were obtained from centenarians and nonagenarians from the longevous region, and elderly participants aged 60–89 from the longevous region, as well as a low centenarian ratio region. The results showed that participants from longevous regions exhibited higher plasma levels of citrate, tyrosine, choline, carnitine, and valine, as well as lower contents of VLDL, lactate, alanine, N-acetyl glycoprotein (NAG), trimethylamine oxide (TMAO), α-glucose, β-glucose, and unsaturated lipids. The differential plasma metabolites were associated with an alteration in glycolysis/gluconeogenesis; aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis in participants from longevous regions. The signature metabolites were associated with higher dietary fiber intake, as well as lower energy and fat intake. The results of the present study demonstrate key longevity signature metabolites in plasma, and the dietary patterns identified provide a basis for further health and longevity research. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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18 pages, 3253 KiB  
Article
Effects of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 on Overweight and the Gut Microbiota in Humans: Randomized, Double-Blinded, Placebo-Controlled Clinical Trial
by Sung-Joon Mo, Kippeum Lee, Hyoung-Ju Hong, Dong-Ki Hong, Seung-Hee Jung, Soo-Dong Park, Jae-Jung Shim and Jung-Lyoul Lee
Nutrients 2022, 14(12), 2484; https://doi.org/10.3390/nu14122484 - 15 Jun 2022
Cited by 17 | Viewed by 4974
Abstract
Obesity and overweight are closely related to diet, and the gut microbiota play an important role in body weight and human health. The aim of this study was to explore how Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 supplementation alleviate obesity by modulating [...] Read more.
Obesity and overweight are closely related to diet, and the gut microbiota play an important role in body weight and human health. The aim of this study was to explore how Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 supplementation alleviate obesity by modulating the human gut microbiome. A randomized, double-blind, placebo-controlled study was conducted on 72 individuals with overweight. Over a 12-week period, probiotic groups consumed 1 × 1010 colony-forming units of HY7601 and KY1032, whereas the placebo group consumed the same product without probiotics. After treatment, the probiotic group displayed a reduction in body weight (p < 0.001), visceral fat mass (p < 0.025), and waist circumference (p < 0.007), and an increase in adiponectin (p < 0.046), compared with the placebo group. Additionally, HY7601 and KY1032 supplementation modulated bacterial gut microbiota characteristics and beta diversity by increasing Bifidobacteriaceae and Akkermansiaceae and decreasing Prevotellaceae and Selenomonadaceae. In summary, HY7601 and KY1032 probiotics exert anti-obesity effects by regulating the gut microbiota; hence, they have therapeutic potential for preventing or alleviating obesity and living with overweight. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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12 pages, 3326 KiB  
Article
Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer’s Disease and All-Cause Dementia: Framingham Offspring Study
by Aleix Sala-Vila, Claudia L. Satizabal, Nathan Tintle, Debora Melo van Lent, Ramachandran S. Vasan, Alexa S. Beiser, Sudha Seshadri and William S. Harris
Nutrients 2022, 14(12), 2408; https://doi.org/10.3390/nu14122408 - 09 Jun 2022
Cited by 13 | Viewed by 25366
Abstract
Docosahexaenoic acid (DHA) might help prevent Alzheimer’s disease (AD). Red blood cell (RBC) status of DHA is an objective measure of long-term dietary DHA intake. In this prospective observational study conducted within the Framingham Offspring Cohort (1490 dementia-free participants aged ≥65 years old), [...] Read more.
Docosahexaenoic acid (DHA) might help prevent Alzheimer’s disease (AD). Red blood cell (RBC) status of DHA is an objective measure of long-term dietary DHA intake. In this prospective observational study conducted within the Framingham Offspring Cohort (1490 dementia-free participants aged ≥65 years old), we examined the association of RBC DHA with incident AD, testing for an interaction with APOE-ε4 carriership. During the follow-up (median, 7.2 years), 131 cases of AD were documented. In fully adjusted models, risk for incident AD in the highest RBC DHA quintile (Q5) was 49% lower compared with the lowest quintile (Q1) (Hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.27, 0.96). An increase in RBC DHA from Q1 to Q5 was predicted to provide an estimated 4.7 additional years of life free of AD. We observed an interaction DHA × APOE-ε4 carriership for AD. Borderline statistical significance for a lower risk of AD was observed per standard deviation increase in RBC DHA (HR: 0.71, 95% CI: 0.51, 1.00, p = 0.053) in APOE-ε4 carriers, but not in non-carriers (HR: 0.85, 95% CI: 0.65, 1.11, p = 0.240). These findings add to the increasing body of literature suggesting a robust association worth exploring dietary DHA as one strategy to prevent or delay AD. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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17 pages, 1344 KiB  
Article
Multilevel Understanding of the Impact of Individual- and School-Level Determinants on Lipid Profiles in Adolescents: The Cross-Level Interaction of Food Environment and Body Mass Index
by Wei-Ting Lin, Yu-Ting Chin, Pei-Wen Wu, Sharon Tsai, Meng-Hsueh Chen, Chiao-I Chang, Yu-Cheng Yang, Chun-Ying Lee, David W. Seal and Chien-Hung Lee
Nutrients 2022, 14(10), 2068; https://doi.org/10.3390/nu14102068 - 15 May 2022
Cited by 1 | Viewed by 1938
Abstract
Adolescents with comparable personal risk factors may have different lipid profiles because of the school’s context. Lipid determinants in adolescents should be considered using a multilevel perspective. This multilevel study investigated the effects of individual-level and school-level factors on lipid profiles in adolescents [...] Read more.
Adolescents with comparable personal risk factors may have different lipid profiles because of the school’s context. Lipid determinants in adolescents should be considered using a multilevel perspective. This multilevel study investigated the effects of individual-level and school-level factors on lipid profiles in adolescents and evaluated the cross-level influence of lipid determinants. A representative adolescent cohort (n = 2727) was randomly selected from 36 schools in three diverse economic areas in Taiwan and assessed for their personal dietary patterns, physical parameters, and lipid profiles. For individual-level factors, both low physical activity and high body mass index (BMI) were associated with elevated triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels, and a sugar-sweetened beverage intake of >500 mL/day was associated with increases of 5.97 and 6.12 mg/dL in LDL-C and TC levels, respectively, compared with abstinence. Regarding school-level factors, students in schools with ≥2 health promotion programs per year had a 5.27 mg/dL lower level of LDL-C than those in schools with 0–1 program, and students in schools with ≥46 food outlets within 600 m of the school had 6.90 and 13.3 mg/dL higher levels of TG and TC, respectively, than those in schools with <46 food outlets. School context modified the individual-level positive correlation between BMI and TG level (the p-value for the random-slope effect was 0.003). In conclusion, individual-level and school-level factors exert a multilevel effect on adolescent lipid profiles. The food environment near the school has a stronger cross-level impact on individual TG levels in adolescents with a high BMI than in those with a normal BMI. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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13 pages, 283 KiB  
Article
Stability and Transformation of Metabolic Syndrome in Adolescents: A Prospective Assessment in Relation to the Change of Cardiometabolic Risk Factors
by Pei-Wen Wu, Yi-Wen Lai, Yu-Ting Chin, Sharon Tsai, Tun-Min Yang, Wei-Ting Lin, Chun-Ying Lee, Wei-Chung Tsai, Hsiao-Ling Huang, David W. Seal, Tsai-Hui Duh and Chien-Hung Lee
Nutrients 2022, 14(4), 744; https://doi.org/10.3390/nu14040744 - 10 Feb 2022
Cited by 5 | Viewed by 1856
Abstract
Underlying pathophysiological mechanisms drive excessive clustering of cardiometabolic risk factors, causing metabolic syndrome (MetS). MetS status may transform as adolescents transition to young adulthood. This study investigated the latent clustering structure and its stability for MetS during adolescence, and assessed the anthropometric and [...] Read more.
Underlying pathophysiological mechanisms drive excessive clustering of cardiometabolic risk factors, causing metabolic syndrome (MetS). MetS status may transform as adolescents transition to young adulthood. This study investigated the latent clustering structure and its stability for MetS during adolescence, and assessed the anthropometric and clinical metabolic determinants for MetS transformation. A community-based representative adolescent cohort (n = 1516) was evaluated for MetS using four diagnostic criteria, and was followed for 2.2 years to identify new-onset MetS. The clustering structure underlying cardiometabolic parameters was stable across adolescence; both comprised a fat—blood pressure (BP)—glucose three-factor structure (total variance explained: 68.8% and 69.7% at baseline and follow-up, respectively). Among adolescents with MetS-negative at baseline, 3.2–4.4% had incident MetS after 2.2 years. Among adolescents with MetS-positive at baseline, 52.0–61.9% experienced MetS remission, and 38.1–48.0% experienced MetS persistence. Increased systolic BP (SBP) was associated with a high MetS incidence risk, while decreased levels of SBP and glucose were associated with MetS remission. Compared with adolescents with a normal metabolic status at baseline, those with an initial abdominal obesity and increased triglycerides level had a 15.0- and 5.7-fold greater risk for persistent abnormality, respectively. Abdominal obesity and low high-density lipoprotein cholesterol are two abnormal MetS components that highly persist during adolescence, and are the intervention targets for reducing the future risk of cardiometabolic disorders. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
11 pages, 1536 KiB  
Article
Examining the Interaction of the Gut Microbiome with Host Metabolism and Cardiometabolic Health in Metabolic Syndrome
by Serena Galié, Christopher Papandreou, Pierre Arcelin, David Garcia, Antoni Palau-Galindo, Laia Gutiérrez-Tordera, Àlex Folch and Mònica Bulló
Nutrients 2021, 13(12), 4318; https://doi.org/10.3390/nu13124318 - 29 Nov 2021
Cited by 5 | Viewed by 2981
Abstract
(1) Background: The microbiota-host cross-talk has been previously investigated, while its role in health is not yet clear. This study aimed to unravel the network of microbial-host interactions and correlate it with cardiometabolic risk factors. (2) Methods: A total of 47 adults with [...] Read more.
(1) Background: The microbiota-host cross-talk has been previously investigated, while its role in health is not yet clear. This study aimed to unravel the network of microbial-host interactions and correlate it with cardiometabolic risk factors. (2) Methods: A total of 47 adults with overweight/obesity and metabolic syndrome from the METADIET study were included in this cross-sectional analysis. Microbiota composition (151 genera) was assessed by 16S rRNA sequencing, fecal (m = 203) and plasma (m = 373) metabolites were profiled. An unsupervised sparse generalized canonical correlation analysis was used to construct a network of microbiota-metabolite interactions. A multi-omics score was derived for each cluster of the network and associated with cardiometabolic risk factors. (3) Results: Five multi-omics clusters were identified. Thirty-one fecal metabolites formed these clusters and were correlated with plasma sphingomyelins, lysophospholipids and medium to long-chain acylcarnitines. Seven genera from Ruminococcaceae and a member from the Desulfovibrionaceae family were correlated with fecal and plasma metabolites. Positive correlations were found between the multi-omics scores from two clusters with cholesterol and triglycerides levels. (4) Conclusions: We identified a correlated network between specific microbial genera and fecal/plasma metabolites in an adult population with metabolic syndrome, suggesting an interplay between gut microbiota and host lipid metabolism on cardiometabolic health. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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13 pages, 676 KiB  
Article
Changes in Circulating Metabolites during Weight Loss and Weight Loss Maintenance in Relation to Cardiometabolic Risk
by Christopher Papandreou, Joanne A. Harrold, Thea T. Hansen, Jason C. G. Halford, Anders Sjödin and Mònica Bulló
Nutrients 2021, 13(12), 4289; https://doi.org/10.3390/nu13124289 - 27 Nov 2021
Cited by 9 | Viewed by 2857
Abstract
(1) Background: There is a substantial lack of knowledge of the biochemical mechanisms by which weight loss and weight regain exert their beneficial and adverse effects, respectively, on cardiometabolic outcomes. We examined associations between changes in circulating metabolites and changes in cardiometabolic risk [...] Read more.
(1) Background: There is a substantial lack of knowledge of the biochemical mechanisms by which weight loss and weight regain exert their beneficial and adverse effects, respectively, on cardiometabolic outcomes. We examined associations between changes in circulating metabolites and changes in cardiometabolic risk factors during diet-induced weight loss and weight loss maintenance. (2) Methods: This prospective analysis of data from the Satiety Innovation (SATIN) study involved adults living with overweight and obesity (mean age=47.5). One hundred sixty-two subjects achieving ≥8% weight loss during an initial 8-week low-calorie diet (LCD) were included in a 12-week weight loss maintenance period. Circulating metabolites (m=123) were profiled using a targeted multiplatform approach. Data were analyzed using multivariate linear regression models. (3) Results: Decreases in the concentrations of several phosphatidylcholines (PCs), sphingomyelins (SMs), and valine were consistently associated with decreases in total (TChol) and low-density lipoprotein cholesterol (LDL-C) levels during the LCD. Increases in PCs and SMs were significantly associated with increases in TChol and LDL-C during the weight loss maintenance period. Decreases and increases in PCs during LCD and maintenance period, respectively, were associated with decreases in the levels of triglycerides. (4) Conclusions: The results of this study suggest that decreases in circulating PCs and SMs during weight loss and the subsequent weight loss maintenance period may decrease the cardiovascular risk through impacting TChol and LDL-C. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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Review

Jump to: Editorial, Research, Other

39 pages, 1074 KiB  
Review
Investigating the Postprandial Metabolome after Challenge Tests to Assess Metabolic Flexibility and Dysregulations Associated with Cardiometabolic Diseases
by Gaïa Lépine, Marie Tremblay-Franco, Sabrine Bouder, Laurianne Dimina, Hélène Fouillet, François Mariotti and Sergio Polakof
Nutrients 2022, 14(3), 472; https://doi.org/10.3390/nu14030472 - 21 Jan 2022
Cited by 16 | Viewed by 3295
Abstract
This review focuses on the added value provided by a research strategy applying metabolomics analyses to assess phenotypic flexibility in response to different nutritional challenge tests in the framework of metabolic clinical studies. We discuss findings related to the Oral Glucose Tolerance Test [...] Read more.
This review focuses on the added value provided by a research strategy applying metabolomics analyses to assess phenotypic flexibility in response to different nutritional challenge tests in the framework of metabolic clinical studies. We discuss findings related to the Oral Glucose Tolerance Test (OGTT) and to mixed meals with varying fat contents and food matrix complexities. Overall, the use of challenge tests combined with metabolomics revealed subtle metabolic dysregulations exacerbated during the postprandial period when comparing healthy and at cardiometabolic risk subjects. In healthy subjects, consistent postprandial metabolic shifts driven by insulin action were reported (e.g., a switch from lipid to glucose oxidation for energy fueling) with similarities between OGTT and mixed meals, especially during the first hours following meal ingestion while differences appeared in a wider timeframe. In populations with expected reduced phenotypic flexibility, often associated with increased cardiometabolic risk, a blunted response on most key postprandial pathways was reported. We also discuss the most suitable statistical tools to analyze the dynamic alterations of the postprandial metabolome while accounting for complexity in study designs and data structure. Overall, the in-depth characterization of the postprandial metabolism and associated phenotypic flexibility appears highly promising for a better understanding of the onset of cardiometabolic diseases. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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29 pages, 1397 KiB  
Review
Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity, Skin Health and Cellular Senescence
by Jacqueline Lena Boyajian, Merry Ghebretatios, Sabrina Schaly, Paromita Islam and Satya Prakash
Nutrients 2021, 13(12), 4550; https://doi.org/10.3390/nu13124550 - 18 Dec 2021
Cited by 41 | Viewed by 13505
Abstract
The role of the microbiome in human aging is important: the microbiome directly impacts aging through the gastrointestinal system. However, the microbial impact on skin has yet to be fully understood. For example, cellular senescence is an intrinsic aging process that has been [...] Read more.
The role of the microbiome in human aging is important: the microbiome directly impacts aging through the gastrointestinal system. However, the microbial impact on skin has yet to be fully understood. For example, cellular senescence is an intrinsic aging process that has been recently associated with microbial imbalance. With age, cells become senescent in response to stress wherein they undergo irreversible growth arrest while maintaining high metabolic activity. An accumulation of senescent cells has been linked to various aging and chronic pathologies due to an overexpression of the senescence-associated secretory phenotype (SASP) comprised of proinflammatory cytokines, chemokines, growth factors, proteases, lipids and extracellular matrix components. In particular, dermatological disorders may be promoted by senescence as the skin is a common site of accumulation. The gut microbiota influences cellular senescence and skin disruption through the gut-skin axis and secretion of microbial metabolites. Metabolomics can be used to identify and quantify metabolites involved in senescence. Moreover, novel anti-senescent therapeutics are warranted given the poor safety profiles of current pharmaceutical drugs. Probiotics and prebiotics may be effective alternatives, considering the relationship between the microbiome and healthy aging. However, further research on gut composition under a senescent status is needed to develop immunomodulatory therapies. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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38 pages, 1342 KiB  
Systematic Review
The Metabolome and the Gut Microbiota for the Prediction of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation: A Systematic Review
by Laura Moschino, Giovanna Verlato, Miriam Duci, Maria Elena Cavicchiolo, Silvia Guiducci, Matteo Stocchero, Giuseppe Giordano, Francesco Fascetti Leon and Eugenio Baraldi
Nutrients 2022, 14(18), 3859; https://doi.org/10.3390/nu14183859 - 18 Sep 2022
Cited by 10 | Viewed by 2656
Abstract
Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell’s [...] Read more.
Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell’s stage II or III), and/or by spontaneous intestinal perforation (SIP) versus healthy controls. Five studies applying metabolomics (43 cases, 95 preterm controls) and 20 applying gut microbiota analysis (254 cases, 651 preterm controls, 22 term controls) were selected. Metabolomic studies utilized NMR spectroscopy or mass spectrometry. An early urinary alanine/histidine ratio >4 showed good sensitivity and predictive value for NEC in one study. Samples collected in proximity to NEC diagnosis demonstrated variable pathways potentially related to NEC. In studies applying untargeted gut microbiota analysis, the sequencing of the V3–V4 or V3 to V5 regions of the 16S rRNA was the most used technique. At phylum level, NEC specimens were characterized by increased relative abundance of Proteobacteria compared to controls. At genus level, pre-NEC samples were characterized by a lack or decreased abundance of Bifidobacterium. Finally, at the species level Bacteroides dorei, Clostridium perfringens and perfringens-like strains dominated early NEC specimens, whereas Clostridium butyricum, neonatale and Propionibacterium acnei those at disease diagnosis. Six studies found a lower Shannon diversity index in cases than controls. A clear separation of cases from controls emerged based on UniFrac metrics in five out of seven studies. Importantly, no studies compared NEC versus SIP. Untargeted metabolomics and gut microbiota analysis are interrelated strategies to investigate NEC pathophysiology and identify potential biomarkers. Expression of quantitative measurements, data sharing via biorepositories and validation studies are fundamental to guarantee consistent comparison of results. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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22 pages, 513 KiB  
Systematic Review
Gut Microbiota-Derived Metabolites and Cardiovascular Disease Risk: A Systematic Review of Prospective Cohort Studies
by Raul Sanchez-Gimenez, Wahiba Ahmed-Khodja, Yesica Molina, Oscar M. Peiró, Gil Bonet, Anna Carrasquer, George A. Fragkiadakis, Mònica Bulló, Alfredo Bardaji and Christopher Papandreou
Nutrients 2022, 14(13), 2654; https://doi.org/10.3390/nu14132654 - 27 Jun 2022
Cited by 23 | Viewed by 3305
Abstract
Gut microbiota-derived metabolites have recently attracted considerable attention due to their role in host-microbial crosstalk and their link with cardiovascular health. The MEDLINE-PubMed and Elsevier’s Scopus databases were searched up to June 2022 for studies evaluating the association of baseline circulating levels of [...] Read more.
Gut microbiota-derived metabolites have recently attracted considerable attention due to their role in host-microbial crosstalk and their link with cardiovascular health. The MEDLINE-PubMed and Elsevier’s Scopus databases were searched up to June 2022 for studies evaluating the association of baseline circulating levels of trimethylamine N-oxide (TMAO), secondary bile acids, short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), tryptophan and indole derivatives, with risk of cardiovascular disease (CVD). A total of twenty-one studies were included in the systematic review after evaluating 1210 non-duplicate records. There were nineteen of the twenty-one studies that were cohort studies and two studies had a nested case–control design. All of the included studies were of high quality according to the “Newcastle–Ottawa Scale”. TMAO was positively associated with adverse cardiovascular events and CVD/all-cause mortality in some, but not all of the included studies. Bile acids were associated with atrial fibrillation and CVD/all-cause mortality, but not with CVD. Positive associations were found between BCAAs and CVD, and between indole derivatives and major adverse cardiovascular events, while a negative association was reported between tryptophan and all-cause mortality. No studies examining the relationship between SCFAs and CVD risk were identified. Evidence from prospective studies included in the systematic review supports a role of microbial metabolites in CVD. Full article
(This article belongs to the Special Issue Nutrition, Metabolites, and Human Health)
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