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Metabolites
Volume 14
Issue 9
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Metabolites, Volume 14, Issue 9 (September 2024) – 50 articles

Cover Story (view full-size image): Juvenile idiopathic arthritis (JIA) is a complex and heterogeneous disease with predisposing genetic and environmental factors. This study utilized plasma metabolomic profiling to identify putative biomarkers of disease. Over 800 plasma metabolites were measured, and altered levels of sphingosine metabolism, sphingomyelins, and other lipids were found to be associated with disease. These metabolic differences discriminated the patients with JIA from the patients without JIA. These findings set the stage for the identification of novel diagnostic biomarkers of disease, as well as the identification of potentially druggable targets, with the promise of a new horizon in personalized medicine for patients with JIA. View this paper
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14 pages, 447 KiB  
Article
Relationship of SOD-1 Activity in Metabolic Syndrome and/or Frailty in Elderly Individuals
by Sylwia Dzięgielewska-Gęsiak, Ewa Wysocka, Edyta Fatyga and Małgorzata Muc-Wierzgoń
Metabolites 2024, 14(9), 514; https://doi.org/10.3390/metabo14090514 - 23 Sep 2024
Viewed by 513
Abstract
Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress also plays a role in frailty (frail) and metabolic syndrome (MetS). Methods: A total of 66 elderly [...] Read more.
Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress also plays a role in frailty (frail) and metabolic syndrome (MetS). Methods: A total of 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed for waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids, and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n = 19), NonMetS-frail (n = 20), MetS-Nonfrail (n = 17), or MetS-frail (n = 10). Results: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggest that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors. Conclusions: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome. These factors provide a nuanced view of how frailty and metabolic syndrome interact with various health parameters, informing both clinical practice and future research directions. Full article
(This article belongs to the Special Issue Inflammation and Oxidative Stress in Age-Related Metabolic Changes and Disorders)
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15 pages, 938 KiB  
Article
Liquid Chromatography/Tandem Mass Spectrometry-Based Simultaneous Analysis of 32 Bile Acids in Plasma and Conventional Biomarker-Integrated Diagnostic Screening Model Development for Hepatocellular Carcinoma
by Minami Yamauchi, Masamitsu Maekawa, Toshihiro Sato, Yu Sato, Masaki Kumondai, Mio Tsuruoka, Jun Inoue, Atsushi Masamune and Nariyasu Mano
Metabolites 2024, 14(9), 513; https://doi.org/10.3390/metabo14090513 - 23 Sep 2024
Viewed by 522
Abstract
Imaging tests, tumor marker (TM) screening, and biochemical tests provide a definitive diagnosis of hepatocellular carcinoma (HCC). However, some patients with HCC may present TM-negative results, warranting a need for developing more sensitive and accurate screening biomarkers. Various diseases exhibit increased blood levels [...] Read more.
Imaging tests, tumor marker (TM) screening, and biochemical tests provide a definitive diagnosis of hepatocellular carcinoma (HCC). However, some patients with HCC may present TM-negative results, warranting a need for developing more sensitive and accurate screening biomarkers. Various diseases exhibit increased blood levels of bile acids, biosynthesized from cholesterol in the liver, and they have been associated with HCC. Herein, we analyzed plasma bile acids using liquid chromatography/tandem mass spectrometry and integrated them with conventional biomarkers to develop a diagnostic screening model for HCC. Plasma samples were obtained from patients diagnosed with chronic hepatitis, hepatic cirrhosis (HC), and HCC. A QTRAP 6500 mass spectrometer and a Nexera liquid chromatograph with a YMC-Triart C18 analytical column were used. The mobile phase A was a 20 mmol/L ammonium formate solution, and mobile phase B was a methanol/acetonitrile mixture (1:1, v/v) with 20 mmol/L ammonium formate. After determining the concentrations of 32 bile acids, statistical analysis and diagnostic screening model development were performed. Plasma concentrations of bile acids differed between sample groups, with significant differences observed between patients with HC and HCC. By integrating bile acid results with conventional biochemical tests, a potential diagnostic screening model for HCC was successfully developed. Future studies should increase the sample size and analyze the data in detail to verify the diagnostic efficacy of the model. Full article
(This article belongs to the Topic Cancer Cell Metabolism (2nd Edition))
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17 pages, 2679 KiB  
Article
Metabolic Predictors of Cardiorespiratory Fitness Responsiveness to Continuous Endurance and High-Intensity Interval Training Programs: The TIMES Study—A Randomized Controlled Trial
by Alex Castro, Antonio Gilberto Ferreira, Aparecida Maria Catai, Matheus Alejandro Bolina Amaral, Claudia Regina Cavaglieri and Mara Patrícia Traina Chacon-Mikahil
Metabolites 2024, 14(9), 512; https://doi.org/10.3390/metabo14090512 - 23 Sep 2024
Viewed by 555
Abstract
Background/Objectives: Cardiorespiratory fitness (CRF) levels significantly modulate the risk of cardiometabolic diseases, aging, and mortality. Nevertheless, there is a substantial interindividual variability in CRF responsiveness to a given standardized exercise dose despite the type of training. Predicting the responsiveness to regular exercise has [...] Read more.
Background/Objectives: Cardiorespiratory fitness (CRF) levels significantly modulate the risk of cardiometabolic diseases, aging, and mortality. Nevertheless, there is a substantial interindividual variability in CRF responsiveness to a given standardized exercise dose despite the type of training. Predicting the responsiveness to regular exercise has the potential to contribute to personalized exercise medicine applications. This study aimed to identify predictive biomarkers for the classification of CRF responsiveness based on serum and intramuscular metabolic levels before continuous endurance training (ET) or high-intensity interval training (HIIT) programs using a randomized controlled trial. Methods: Forty-three serum and seventy intramuscular (vastus lateralis) metabolites were characterized and quantified via proton nuclear magnetic resonance (1H NMR), and CRF levels (expressed in METs) were measured in 70 sedentary young men (age: 23.7 ± 3.0 years; BMI: 24.8 ± 2.5 kg·m−2), at baseline and post 8 weeks of the ET, HIIT, and control (CO) periods. A multivariate binary logistic regression model was used to classify individuals at baseline as Responders or Non-responders to CRF gains after the training programs. Results: CRF responses ranged from 0.9 to 3.9 METs for ET, 1.1 to 4.7 METs for HIIT, and −0.9 to 0.2 METs for CO. The frequency of Responder/Non-responder individuals between ET (76.7%/23.3%) and HIIT (90.0%/10.0%) programs was similar (p = 0.166). The model based on serum O-acetylcarnitine levels [OR (odds ratio) = 4.72, p = 0.012] classified Responder/Non-responders individuals to changes in CRF regardless of the training program with 78.0% accuracy (p = 0.006), while the intramuscular model based on creatinine levels (OR = 4.53, p = 0.0137) presented 72.3% accuracy (p = 0.028). Conclusions: These results highlight the potential value of serum and intramuscular metabolites as biomarkers for the classification of CRF responsiveness previous to different aerobic training programs. Full article
(This article belongs to the Special Issue Metabolomic Advances in Promoting Exercise-Induced Metabolic Changes)
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14 pages, 3861 KiB  
Article
Comprehensive Secondary Metabolite Profiling and Antioxidant Activity of Aqueous and Ethanol Extracts of Neolamarckia cadamba (Roxb.) Bosser Fruits
by Lin Yang, Liyan Wu, Yongxin Li, Yuhui Yang, Yuting Gu, Jialin Yang, Luzy Zhang and Fanxin Meng
Metabolites 2024, 14(9), 511; https://doi.org/10.3390/metabo14090511 - 21 Sep 2024
Viewed by 446
Abstract
Background: Neolamarckia cadamba (Rubiaceae) is a well-recognized medicinal plant with recorded therapeutical attributes. However, a thorough assessment of active compounds in its fruits is lacking, limiting their use and valorization in pharmacological industries. Methods: Thus, this study investigated variations in the fruits’ secondary [...] Read more.
Background: Neolamarckia cadamba (Rubiaceae) is a well-recognized medicinal plant with recorded therapeutical attributes. However, a thorough assessment of active compounds in its fruits is lacking, limiting their use and valorization in pharmacological industries. Methods: Thus, this study investigated variations in the fruits’ secondary metabolite (SM) profiles, as well as antioxidant activities in aqueous (WA) and ethanol (ET) extracts. Results: Liquid chromatography–electrospray ionization tandem mass spectrometry identified 541 SMs, of which 14 and 1 (di-O-glucosylquinic acid) were specifically detected in ET and WA, respectively. Phenolic acids (36.97%), flavonoids (28.10%), terpenoids (12.20%), and alkaloids (9.98%) were the dominant SMs. The SM profiles of the fruits in WA and ET were quite different. We revealed 198 differentially extracted (DE) metabolites between WA and ET, including 62 flavonoids, 57 phenolic acids, 45 terpenoids, 14 alkaloids, etc. Most DE flavones (36 out of 40), terpenoids (45 out of 45), and alkaloids (12 out of 14) had higher content in ET. Catechin and its derivatives, procyanidins, and tannins had higher content in WA. ABTS and DPPH assays showed that the antioxidant activity of ET was significantly higher than that of WA. Conclusions: Our findings will facilitate the efficient extraction and evaluation of specific active compounds in N. cadamba. Full article
(This article belongs to the Section Plant Metabolism)
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14 pages, 2401 KiB  
Article
Predicting the Association of Metabolites with Both Pathway Categories and Individual Pathways
by Erik D. Huckvale and Hunter N. B. Moseley
Metabolites 2024, 14(9), 510; https://doi.org/10.3390/metabo14090510 - 21 Sep 2024
Viewed by 448
Abstract
Metabolism is a network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic [...] Read more.
Metabolism is a network of chemical reactions that sustain cellular life. Parts of this metabolic network are defined as metabolic pathways containing specific biochemical reactions. Products and reactants of these reactions are called metabolites, which are associated with certain human-defined metabolic pathways. Metabolic knowledgebases, such as the Kyoto Encyclopedia of Gene and Genomes (KEGG) contain metabolites, reactions, and pathway annotations; however, such resources are incomplete due to current limits of metabolic knowledge. To fill in missing metabolite pathway annotations, past machine learning models showed some success at predicting the KEGG Level 2 pathway category involvement of metabolites based on their chemical structure. Here, we present the first machine learning model to predict metabolite association to more granular KEGG Level 3 metabolic pathways. We used a feature and dataset engineering approach to generate over one million metabolite-pathway entries in the dataset used to train a single binary classifier. This approach produced a mean Matthews correlation coefficient (MCC) of 0.806 ± 0.017 SD across 100 cross-validation iterations. The 172 Level 3 pathways were predicted with an overall MCC of 0.726. Moreover, metabolite association with the 12 Level 2 pathway categories was predicted with an overall MCC of 0.891, representing significant transfer learning from the Level 3 pathway entries. These are the best metabolite pathway prediction results published so far in the field. Full article
(This article belongs to the Special Issue Machine Learning Applications in Metabolomics Analysis)
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21 pages, 7584 KiB  
Article
Investigating the Mechanisms of 15-PGDH Inhibitor SW033291 in Improving Type 2 Diabetes Mellitus: Insights from Metabolomics and Transcriptomics
by Yuanfeng Huang, Mingjie Liang, Yiwen Liao, Zirui Ji, Wanfen Lin, Xiangjin Pu, Lexun Wang and Weixuan Wang
Metabolites 2024, 14(9), 509; https://doi.org/10.3390/metabo14090509 - 20 Sep 2024
Viewed by 398
Abstract
This study focused on exploring the effects of SW033291, an inhibitor of 15-hydroxyprostaglandin dehydrogenase, on type 2 diabetes mellitus (T2DM) mice from a comprehensive perspective. Studies have demonstrated that SW033291 benefits tissue repair, organ function, and muscle mass in elderly mice. Our recent [...] Read more.
This study focused on exploring the effects of SW033291, an inhibitor of 15-hydroxyprostaglandin dehydrogenase, on type 2 diabetes mellitus (T2DM) mice from a comprehensive perspective. Studies have demonstrated that SW033291 benefits tissue repair, organ function, and muscle mass in elderly mice. Our recent investigation initially reported the beneficial effect of SW033291 on T2DM progression. Herein, we used a T2DM mouse model induced by a high-fat diet and streptozotocin injection. Then, serum and liver metabolomics, as well as liver transcriptomic analyses, were performed to provide a systematic perspective of the SW033291-ameliorated T2DM. The results indicate SW033291 improved T2DM by regulating steroid hormone biosynthesis and linoleic/arachidonic acid metabolism. Furthermore, integrated transcriptomic and metabolomic analyses suggested that key genes and metabolites such as Cyp2c55, Cyp3a11, Cyp21a1, Myc, Gstm1, Gstm3, 9,10-dihydroxyoctadecenoic acid, 11-dehydrocorticosterone, and 12,13-dihydroxy-9Z-octadecenoic acid played crucial roles in these pathways. qPCR analysis validated the significant decreases in the hepatic gene expressions of Cyp2c55, Cyp3a11, Myc, Gstm1, and Gstm3 in the T2DM mice, which were reversed following SW033291 treatment. Meanwhile, the elevated mRNA level of Cyp21a1 in T2DM mice was decreased after SW033291 administration. Taken together, our findings suggest that SW033291 has promising potential in alleviating T2DM and could be a novel therapeutic candidate. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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32 pages, 1638 KiB  
Review
Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy
by Caroline Brito Nunes, Maria Carolina Borges, Rachel M. Freathy, Deborah A. Lawlor, Elisabeth Qvigstad, David M. Evans and Gunn-Helen Moen
Metabolites 2024, 14(9), 508; https://doi.org/10.3390/metabo14090508 - 20 Sep 2024
Viewed by 791
Abstract
Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion [...] Read more.
Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. Methods: In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. Results/Conclusions: Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies. Full article
(This article belongs to the Special Issue Glucose Metabolism in Pregnancy)
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17 pages, 7634 KiB  
Article
Rice Varieties Intercropping Induced Soil Metabolic and Microbial Recruiting to Enhance the Rice Blast (Magnaporthe Oryzae) Resistance
by Xiao-Qiao Zhu, Mei Li, Rong-Ping Li, Wen-Qiang Tang, Yun-Yue Wang, Xiao Fei, Ping He and Guang-Yu Han
Metabolites 2024, 14(9), 507; https://doi.org/10.3390/metabo14090507 - 20 Sep 2024
Viewed by 481
Abstract
[Background] Intercropping is considered an effective approach to defending rice disease. [Objectives/Methods] This study aimed to explore the resistance mechanism of rice intraspecific intercropping by investigating soil metabolites and their regulation on the rhizosphere soil microbial community using metabolomic and microbiome analyses. [Results] [...] Read more.
[Background] Intercropping is considered an effective approach to defending rice disease. [Objectives/Methods] This study aimed to explore the resistance mechanism of rice intraspecific intercropping by investigating soil metabolites and their regulation on the rhizosphere soil microbial community using metabolomic and microbiome analyses. [Results] The results showed that the panicle blast disease occurrence of the resistant variety Shanyou63 (SY63) and the susceptible variety Huangkenuo (HKN) were both decreased in the intercropping compared to monoculture. Notably, HKN in the intercropping system exhibited significantly decreased disease incidence and increased disease resistance-related enzyme protease activity. KEGG annotation from soil metabolomics analysis revealed that phenylalanine metabolic pathway, phenylalanine, tyrosine, and tryptophan biosynthesis pathway, and fructose and mannose metabolic pathway were the key pathways related to rice disease resistance. Soil microbiome analysis indicated that the bacterial genera Nocardioides, Marmoricola, Luedemannella, and Desulfomonile were significantly enriched in HKN after intercropping, while SY63 experienced a substantial accumulation of Ruminiclostridium and Cellulomonas. Omics-based correlation analysis highlighted that the community assembly of Cellulomonas and Desulfomonile significantly affected the content of the metabolites D-sorbitol, D-mannitol, quinic acid, which further proved that quinic acid had a significantly inhibitory effect on the mycelium growth of Magnaporthe oryzae, and these three metabolites had a significant blast control effect. The optimal rice blast-control efficiency on HKN was 51.72%, and Lijiangxintuanheigu (LTH) was 64.57%. [Conclusions] These findings provide a theoretical basis for rice varieties intercropping and sustainable rice production, emphasizing the novelty of the study in elucidating the underlying mechanisms of intercropping-mediated disease resistance. Full article
(This article belongs to the Section Microbiology and Ecological Metabolomics)
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15 pages, 1409 KiB  
Article
Exploring the Metabolism of Flubrotizolam, a Potent Thieno-Triazolo Diazepine, Using Human Hepatocytes and High-Resolution Mass Spectrometry
by Prince Sellase Gameli, Johannes Kutzler, Diletta Berardinelli, Jeremy Carlier, Volker Auwärter and Francesco Paolo Busardò
Metabolites 2024, 14(9), 506; https://doi.org/10.3390/metabo14090506 - 19 Sep 2024
Viewed by 601
Abstract
Background: The abuse of psychoactive substances presents challenges in clinical and forensic toxicology. The emergence of novel and potent drugs that pose significant health risks, in particular towards frequent abusers and users unaware of the ingredients, further complicates the situation. Designer benzodiazepines have [...] Read more.
Background: The abuse of psychoactive substances presents challenges in clinical and forensic toxicology. The emergence of novel and potent drugs that pose significant health risks, in particular towards frequent abusers and users unaware of the ingredients, further complicates the situation. Designer benzodiazepines have become a fast-growing subgroup of these new psychoactive substances (NPSs), and their overdose may potentially turn fatal, especially when combined with other central nervous system depressants. In 2021, flubrotizolam, a potent thieno-triazolo designer benzodiazepine, emerged on the illicit market, available online as a “research chemical”. The identification of markers of consumption for this designer benzodiazepine is essential in analytical toxicology, especially in clinical and forensic cases. Methods: We therefore aimed to identify biomarkers of flubrotizolam uptake in ten-donor-pooled human hepatocytes, applying liquid chromatography high-resolution mass spectrometry and software-aided data mining supported by in silico prediction tools. Results: Prediction studies resulted in 10 and 13 first- and second-generation metabolites, respectively, mainly transformed through hydroxylation and sulfation, methylation, and glucuronidation reactions. We identified six metabolites after 3 h human hepatocyte incubation: two hydroxylated metabolites (α- and 6-hydroxy-flubrotizolam), two 6-hydroxy-glucuronides, a reduced-hydroxy-N-glucuronide, and an N-glucuronide. Conclusions: We suggest detecting flubrotizolam and its hydroxylated metabolites as markers of consumption after the glucuronide hydrolysis of biological samples. The results are consistent with the in vivo metabolism of brotizolam, a medically used benzodiazepine and a chloro-phenyl analog of flubrotizolam. Full article
(This article belongs to the Special Issue Metabolite Profiling of Novel Psychoactive Substances)
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13 pages, 2072 KiB  
Article
Urinary Biomarkers of Strawberry and Blueberry Intake
by Ya Gao, Rebecca Finlay, Xiaofei Yin and Lorraine Brennan
Metabolites 2024, 14(9), 505; https://doi.org/10.3390/metabo14090505 - 18 Sep 2024
Viewed by 466
Abstract
Introduction There is increasing interest in food biomarkers to address the shortcomings of self-reported dietary assessments. Berries are regarded as important fruits worldwide; however, there are no well-validated biomarkers of berry intake. Thus, the objective of this study is to identify urinary biomarkers [...] Read more.
Introduction There is increasing interest in food biomarkers to address the shortcomings of self-reported dietary assessments. Berries are regarded as important fruits worldwide; however, there are no well-validated biomarkers of berry intake. Thus, the objective of this study is to identify urinary biomarkers of berry intake. Methods For the discovery study, participants consumed 192 g strawberries with 150 g blueberries, and urine samples were collected at 2, 4, 6, and 24 h post-consumption. A dose–response study was performed, whereby participants consumed three portions (78 g, 278 g, and 428 g) of mixed strawberries and blueberries. The urine samples were profiled by an untargeted LC-MS metabolomics approach in the positive and negative modes. Results Statistical analysis of the data revealed that 39 features in the negative mode and 15 in the positive mode significantly increased between fasting and 4 h following mixed berry intake. Following the analysis of the dose–response data, 21 biomarkers showed overall significance across the portions of berry intake. Identification of the biomarkers was performed using fragmentation matches in the METLIN, HMDB, and MoNA databases and in published papers, confirmed where possible with authentic standards. Conclusions The ability of the panel of biomarkers to assess intake was examined, and the predictability was good, laying the foundations for the development of biomarker panels. Full article
(This article belongs to the Section Food Metabolomics)
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14 pages, 2682 KiB  
Article
Impact of Microplastic Exposure on Blood Glucose Levels and Gut Microbiota: Differential Effects under Normal or High-Fat Diet Conditions
by Manjin Xu, Huixia Niu, Lizhi Wu, Mingluan Xing, Zhe Mo, Zhijian Chen, Xueqing Li and Xiaoming Lou
Metabolites 2024, 14(9), 504; https://doi.org/10.3390/metabo14090504 - 18 Sep 2024
Viewed by 721
Abstract
Microplastics are emerging pollutants that have garnered significant attention, with evidence suggesting their association with the pathogenesis of type 2 diabetes mellitus. In order to assess the impact of polystyrene microplastic exposure on alterations in the gut microbiota and the subsequent implications for [...] Read more.
Microplastics are emerging pollutants that have garnered significant attention, with evidence suggesting their association with the pathogenesis of type 2 diabetes mellitus. In order to assess the impact of polystyrene microplastic exposure on alterations in the gut microbiota and the subsequent implications for glucose dysregulation under different dietary conditions in mice, we investigated the effects and disparities in the blood glucose levels induced by polystyrene microplastic exposure in mice fed a high-fat diet versus those fed a normal diet. Using 16S rRNA sequencing and bioinformatics analyses, we explored the dynamic changes and discrepancies in the gut microbiota stability induced by polystyrene microplastic exposure under varied dietary conditions, and we screened for gut genera associated with the potential of polystyrene microplastics to disrupt glucose homeostasis. Our findings indicate that a high-fat diet resulted in abnormal mouse body weight, energy intake, blood glucose levels and related metabolic parameters. Additionally, polystyrene microplastic exposure exacerbated the glucose metabolism disorders induced by a high-fat diet. Furthermore, the composition and diversity of the mouse gut microbiota were significantly altered following microplastic exposure, with 11 gut genera exhibiting a differential presence between mice fed a high-fat diet combined with microplastic exposure compared to those fed a normal diet with microplastic exposure. Moreover, Ucg-009 played an intermediary role in the association between a high-fat diet and the fasting blood glucose. Hence, our study demonstrates that polystyrene microplastic exposure exacerbates high-fat diet-induced glucose metabolism disorders, whereas its impact on the blood glucose under normal dietary conditions is not significant, highlighting the differential influence attributable to distinct alterations in characteristic gut genera. Full article
(This article belongs to the Special Issue Effects of Environmental Exposure on Host and Microbial Metabolism)
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17 pages, 5594 KiB  
Article
Metabolomic and Physiological Analyses Reveal the Effects of Different Storage Conditions on Sinojackia xylocarpa Hu Seeds
by Hao Cai and Yongbao Shen
Metabolites 2024, 14(9), 503; https://doi.org/10.3390/metabo14090503 - 18 Sep 2024
Viewed by 598
Abstract
Backgrounds: Sinojackia xylocarpa Hu is a deciduous tree in the Styracaceae family, and it is classified as a Class II endangered plant in China. Seed storage technology is an effective means of conserving germplasm resources, but the effects of different storage conditions on [...] Read more.
Backgrounds: Sinojackia xylocarpa Hu is a deciduous tree in the Styracaceae family, and it is classified as a Class II endangered plant in China. Seed storage technology is an effective means of conserving germplasm resources, but the effects of different storage conditions on the quality and associated metabolism of S. xylocarpa seeds remain unclear. This study analyzed the physiological and metabolic characteristics of S. xylocarpa seeds under four storage conditions. Results: Our findings demonstrate that reducing seed moisture content and storage temperature effectively prolongs storage life. Seeds stored under that condition exhibited higher internal nutrient levels, lower endogenous abscisic acid (ABA) hormone levels, and elevated gibberellic acid (GA3) levels. Additionally, 335 metabolites were identified under four different storage conditions. The analysis indicates that S. xylocarpa seeds extend seed longevity and maintain cellular structural stability mainly by regulating the changes in metabolites related to lipid, amino acid, carbohydrate, and carotenoid metabolic pathways under the storage conditions of a low temperature and low seed moisture. Conclusions: These findings provide new insights at the physiological and metabolic levels into how these storage conditions extend seed longevity while also offering effective storage strategies for preserving the germplasm resources of S. xylocarpa. Full article
(This article belongs to the Section Plant Metabolism)
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13 pages, 628 KiB  
Article
Relationship between Body Adiposity Indices and Reversal of Metabolically Unhealthy Obesity 6 Months after Roux-en-Y Gastric Bypass
by Mariana Luna, Silvia Pereira, Carlos Saboya and Andrea Ramalho
Metabolites 2024, 14(9), 502; https://doi.org/10.3390/metabo14090502 - 18 Sep 2024
Viewed by 509
Abstract
The factors determining the reversal of metabolically unhealthy obesity (MUO) to metabolically healthy obesity (MHO) after Roux-en-Y gastric bypass (RYGB) are not completely elucidated. The present study aims to evaluate body adiposity and distribution, through different indices, according to metabolic phenotypes before and [...] Read more.
The factors determining the reversal of metabolically unhealthy obesity (MUO) to metabolically healthy obesity (MHO) after Roux-en-Y gastric bypass (RYGB) are not completely elucidated. The present study aims to evaluate body adiposity and distribution, through different indices, according to metabolic phenotypes before and 6 months after RYGB, and the relationship between these indices and transition from MUO to MHO. This study reports a prospective longitudinal study on adults with obesity who were evaluated before (T0) and 6 months (T1) after RYGB. Bodyweight, height, waist circumference (WC), BMI, waist-to-height ratio (WHR), total cholesterol (TC), HDL-c, LDL-c, triglycerides, insulin, glucose, HbA1c and HOMA-IR were evaluated. The visceral adiposity index (VAI), the conicity index (CI), the lipid accumulation product (LAP), CUN-BAE and body shape index (ABSI) were calculated. MUO was classified based on insulin resistance. MUO at T0 with transition to MHO at T1 formed the MHO-t group MHO and MUO at both T0 and T1 formed the MHO-m and MUO-m groups, respectively. At T0, 37.3% of the 62 individuals were classified as MHO and 62.7% as MUO. Individuals in the MUO-T0 group had higher blood glucose, HbA1c, HOMA-IR, insulin, TC and LDL-c compared to those in the MHO-T0 group. Both groups showed significant improvement in biochemical and body variables at T1. After RYGB, 89.2% of MUO-T0 became MHO (MHO-t). The MUO-m group presented higher HOMA-IR, insulin and VAI, compared to the MHO-m and MHO-t groups. CI and ABSI at T0 correlated with HOMA-IR at T1 in the MHO-t and MHO-m groups. CI and ABSI, indicators of visceral fat, are promising for predicting post-RYGB metabolic improvement. Additional studies are needed to confirm the sustainability of MUO reversion and its relationship with these indices. Full article
(This article belongs to the Special Issue Exploring Pathological Mechanisms in Obesity, Diabetes, and Metabolic Syndrome)
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18 pages, 4848 KiB  
Article
Implementation of Machine Learning-Based System for Early Diagnosis of Feline Mammary Carcinomas through Blood Metabolite Profiling
by Vidhi Kulkarni, Igor F. Tsigelny and Valentina L. Kouznetsova
Metabolites 2024, 14(9), 501; https://doi.org/10.3390/metabo14090501 - 17 Sep 2024
Viewed by 538
Abstract
Background: Feline mammary carcinoma (FMC) is a prevalent and fatal carcinoma that predominantly affects unspayed female cats. FMC is the third most common carcinoma in cats but is still underrepresented in research. Current diagnosis methods include physical examinations, imaging tests, and fine-needle aspiration. [...] Read more.
Background: Feline mammary carcinoma (FMC) is a prevalent and fatal carcinoma that predominantly affects unspayed female cats. FMC is the third most common carcinoma in cats but is still underrepresented in research. Current diagnosis methods include physical examinations, imaging tests, and fine-needle aspiration. The diagnosis through these methods is sometimes delayed and unreliable, leading to increased chances of mortality. Objectives: The objective of this study was to identify the biomarkers, including blood metabolites and genes, related to feline mammary carcinoma, study their relationships, and develop a machine learning (ML) model for the early diagnosis of the disease. Methods: We analyzed the blood metabolites of felines with mammary carcinoma using the pathway analysis feature in MetaboAnalyst software, v. 5.0. We utilized machine-learning (ML) methods to recognize FMC using the blood metabolites of sick patients. Results: The metabolic pathways that were elucidated to be associated with this disease include alanine, aspartate and glutamate metabolism, Glutamine and glutamate metabolism, Arginine biosynthesis, and Glycerophospholipid metabolism. Furthermore, we also elucidated several genes that play a significant role in the development of FMC, such as ERBB2, PDGFA, EGFR, FLT4, ERBB3, FIGF, PDGFC, PDGFB through STRINGdb, a database of known and predicted protein-protein interactions, and MetaboAnalyst 5.0. The best-performing ML model was able to predict metabolite class with an accuracy of 85.11%. Conclusion: Our findings demonstrate that the identification of the biomarkers associated with FMC and the affected metabolic pathways can aid in the early diagnosis of feline mammary carcinoma. Full article
(This article belongs to the Special Issue Metabolomics and Computational Research on Drugs and Diseases)
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14 pages, 2039 KiB  
Article
Metabolomic Effects of Liraglutide Therapy on the Plasma Metabolomic Profile of Patients with Obesity
by Assim A. Alfadda, Anas M. Abdel Rahman, Hicham Benabdelkamel, Reem AlMalki, Bashayr Alsuwayni, Abdulaziz Alhossan, Madhawi M. Aldhwayan, Ghalia N. Abdeen, Alexander Dimitri Miras and Afshan Masood
Metabolites 2024, 14(9), 500; https://doi.org/10.3390/metabo14090500 - 17 Sep 2024
Viewed by 479
Abstract
Background: Liraglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP1RA), is a well-established anti-diabetic drug, has also been approved for the treatment of obesity at a dose of 3 mg. There are a limited number of studies in the literature that have looked at [...] Read more.
Background: Liraglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP1RA), is a well-established anti-diabetic drug, has also been approved for the treatment of obesity at a dose of 3 mg. There are a limited number of studies in the literature that have looked at changes in metabolite levels before and after liraglutide treatment in patients with obesity. To this end, in the present study we aimed to explore the changes in the plasma metabolomic profile, using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in patients with obesity. Methods: A single-center prospective study was undertaken to evaluate the effectiveness of 3 mg liraglutide therapy in twenty-three patients (M/F: 8/15) with obesity, mean BMI 40.81 ± 5.04 kg/m2, and mean age of 36 ± 10.9 years, in two groups: at baseline (pre-treatment) and after 12 weeks of treatment (post-treatment). An untargeted metabolomic profiling was conducted in plasma from the pre-treatment and post-treatment groups using LC-HRMS, along with bioinformatics analysis using ingenuity pathway analysis (IPA). Results: The metabolomics analysis revealed a significant (FDR p-value ≤ 0.05, FC 1.5) dysregulation of 161 endogenous metabolites (97 upregulated and 64 downregulated) with distinct separation between the two groups. Among the significantly dysregulated metabolites, the majority of them were identified as belonging to the class of oxidized lipids (oxylipins) that includes arachidonic acid and its derivatives, phosphorglycerophosphates, N-acylated amino acids, steroid hormones, and bile acids. The biomarker analysis conducted using MetaboAnalyst showed PGP (a21:0/PG/F1alpha), an oxidized lipid, as the first metabolite among the list of the top 15 biomarkers, followed by cysteine and estrone. The IPA analysis showed that the dysregulated metabolites impacted the pathway related to cell signaling, free radical scavenging, and molecular transport, and were focused around the dysregulation of NF-κB, ERK, MAPK, PKc, VEGF, insulin, and pro-inflammatory cytokine signaling pathways. Conclusions: The findings suggest that liraglutide treatment reduces inflammation and modulates lipid metabolism and oxidative stress. Our study contributes to a better understanding of the drug’s multifaceted impact on overall metabolism in patients with obesity. Full article
(This article belongs to the Special Issue Metabolomics in Human Diseases and Health)
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18 pages, 3605 KiB  
Article
Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis
by Amar Kumar, Joshua Tatarian, Valentina Shakhnovich, Rachel L. Chevalier, Marc Sudman, Daniel J. Lovell, Susan D. Thompson, Mara L. Becker and Ryan S. Funk
Metabolites 2024, 14(9), 499; https://doi.org/10.3390/metabo14090499 - 16 Sep 2024
Viewed by 743
Abstract
Identification of disease and therapeutic biomarkers remains a significant challenge in the early diagnosis and effective treatment of juvenile idiopathic arthritis (JIA). In this study, plasma metabolomic profiling was conducted to identify disease-related metabolic biomarkers associated with JIA. Plasma samples from treatment-naïve JIA [...] Read more.
Identification of disease and therapeutic biomarkers remains a significant challenge in the early diagnosis and effective treatment of juvenile idiopathic arthritis (JIA). In this study, plasma metabolomic profiling was conducted to identify disease-related metabolic biomarkers associated with JIA. Plasma samples from treatment-naïve JIA patients and non-JIA reference patients underwent global metabolomic profiling across discovery (60 JIA, 60 non-JIA) and replication (49 JIA, 38 non-JIA) cohorts. Univariate analysis identified significant metabolites (q-value ≤ 0.05), followed by enrichment analysis using ChemRICH and metabolic network mapping with MetaMapp and Cytoscape. Receiver operating characteristic (ROC) analysis determined the top discriminating biomarkers based on area under the curve (AUC) values. A total of over 800 metabolites were measured, consisting of 714 known and 155 unknown compounds. In the discovery cohort, 587 metabolites were significantly altered in JIA patients compared with the reference population (q < 0.05). In the replication cohort, 288 metabolites were significantly altered, with 78 overlapping metabolites demonstrating the same directional change in both cohorts. JIA was associated with a notable increase in plasma levels of sphingosine metabolites and fatty acid ethanolamides and decreased plasma levels of sarcosine, iminodiacetate, and the unknown metabolite X-12462. Chemical enrichment analysis identified cycloparaffins in the form of naproxen and its metabolites, unsaturated lysophospholipids, saturated phosphatidylcholines, sphingomyelins, ethanolamines, and saturated ceramides as the top discriminating biochemical clusters. ROC curve analysis identified 11 metabolites classified as highly discriminatory based on an AUC > 0.90, with the top discriminating metabolite being sphinganine-1-phosphate (AUC = 0.98). This study identifies specific metabolic changes in JIA, particularly within sphingosine metabolism, through both discovery and replication cohorts. Plasma metabolomic profiling shows promise in pinpointing JIA-specific biomarkers, differentiating them from those in healthy controls and Crohn’s disease, which may improve diagnosis and treatment. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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21 pages, 6380 KiB  
Article
Combined Metabolome and Transcriptome Analyses of Maize Leaves Reveal Global Effect of Biochar on Mechanisms Involved in Anti-Herbivory to Spodoptera frugiperda
by Tianjun He, Lin Chen, Yingjun Wu, Jinchao Wang, Quancong Wu, Jiahao Sun, Chaohong Ding, Tianxing Zhou, Limin Chen, Aiwu Jin, Yang Li and Qianggen Zhu
Metabolites 2024, 14(9), 498; https://doi.org/10.3390/metabo14090498 - 14 Sep 2024
Viewed by 459
Abstract
Fall armyworm (FAW, Spodoptera frugiperda) has now spread to more than 26 Chinese provinces. The government is working with farmers and researchers to find ways to prevent and control this pest. The use of biochar is one of the economic and environmentally [...] Read more.
Fall armyworm (FAW, Spodoptera frugiperda) has now spread to more than 26 Chinese provinces. The government is working with farmers and researchers to find ways to prevent and control this pest. The use of biochar is one of the economic and environmentally friendly strategies to increase plant growth and improve pest resistance. We tested four v/v combinations of bamboo charcoal with coconut bran [BC1 (10:1), BC2(30:1), BC3(50:1)] against a control (CK) in maize. We found that plant height, stem thickness, fresh weight and chlorophyll content were significantly higher in BC2, in addition to the lowest FAW survival %. We then compared the metabolome and transcriptome profiles of BC2 and CK maize plants under FAW herbivory. Our results show that the levels of flavonoids, amino acids and derivatives, nucleotides and derivatives and most phenolic acids decreased, while terpenoids, organic acids, lipids and defense-related hormones increased in BC-grown maize leaves. Transcriptome sequencing revealed consistent expression profiles of genes enriched in these pathways. We also observed the increased expression of genes related to abscisic acid, jasmonic acid, auxin and MAPK signaling. Based on these observations, we discussed the possible pathways involved in maize against FAW herbivory. We conclude that bamboo charcoal induces anti-herbivory responses in maize leaves. Full article
(This article belongs to the Special Issue Plant Biotic and Abiotic Stress Responses and Tolerance: Phytohormonal and Metabolic Insights)
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17 pages, 3031 KiB  
Article
Functional Muffins Exert Bifidogenic Effects along with Highly Product-Specific Effects on the Human Gut Microbiota Ex Vivo
by Stef Deyaert, Jonas Poppe, Lam Dai Vu, Aurélien Baudot, Sarah Bubeck, Thomas Bayne, Kiran Krishnan, Morgan Giusto, Samuel Moltz and Pieter Van den Abbeele
Metabolites 2024, 14(9), 497; https://doi.org/10.3390/metabo14090497 - 14 Sep 2024
Viewed by 777
Abstract
GoodBiome™ Foods are functional foods containing a probiotic (Bacillus subtilis HU58™) and prebiotics (mainly inulin). Their effects on the human gut microbiota were assessed using ex vivo SIFR® technology, which has been validated to provide clinically predictive insights. GoodBiome™ Foods (BBM/LCM/OSM) [...] Read more.
GoodBiome™ Foods are functional foods containing a probiotic (Bacillus subtilis HU58™) and prebiotics (mainly inulin). Their effects on the human gut microbiota were assessed using ex vivo SIFR® technology, which has been validated to provide clinically predictive insights. GoodBiome™ Foods (BBM/LCM/OSM) were subjected to oral, gastric, and small intestinal digestion/absorption, after which their impact on the gut microbiome of four adults was assessed (n = 3). All GoodBiome™ Foods boosted health-related SCFA acetate (+13.1/14.1/13.8 mM for BBM/LCM/OSM), propionate (particularly OSM; +7.4/7.5/8.9 mM for BBM/LCM/OSM) and butyrate (particularly BBM; +2.6/2.1/1.4 mM for BBM/LCM/OSM). This is related to the increase in Bifidobacterium species (B. catenulatum, B. adolescentis, B. pseudocatenulatum), Coprococcus catus and Bacteroidetes members (Bacteroides caccae, Phocaeicola dorei, P. massiliensis), likely mediated via inulin. Further, the potent propionogenic potential of OSM related to increased Bacteroidetes members known to ferment oats (s key ingredient of OSM), while the butyrogenic potential of BBM related to a specific increase in Anaerobutyricum hallii, a butyrate producer specialized in the fermentation of erythritol (key ingredient of BBM). In addition, OSM/BBM suppressed the pathogen Clostridioides difficile, potentially due to inclusion of HU58™ in GoodBiome™ Foods. Finally, all products enhanced a spectrum of metabolites well beyond SCFA, including vitamins (B3/B6), essential amino acids, and health-related metabolites such as indole-3-propionic acid. Overall, the addition of specific ingredients to complex foods was shown to specifically modulate the gut microbiome, potentially contributing to health benefits. Noticeably, our findings contradict a recent in vitro study, underscoring the critical role of employing a physiologically relevant digestion/absorption procedure for a more accurate evaluation of the microbiome-modulating potential of complex foods. Full article
(This article belongs to the Special Issue Natural Metabolites on Gut Microbiome Modulation)
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45 pages, 1381 KiB  
Review
Animal Food Products to Support Human Nutrition and to Boost Human Health: The Potential of Feedstuffs Resources and Their Metabolites as Health-Promoters
by Mario Cuchillo-Hilario, Mareli-Itzel Fournier-Ramírez, Margarita Díaz Martínez, Sara Montaño Benavides, María-Concepción Calvo-Carrillo, Silvia Carrillo Domínguez, María-Elena Carranco-Jáuregui, Elizabeth Hernández-Rodríguez, Patricia Mora-Pérez, Yesica R. Cruz-Martínez and Claudia Delgadillo-Puga
Metabolites 2024, 14(9), 496; https://doi.org/10.3390/metabo14090496 - 13 Sep 2024
Viewed by 538
Abstract
Recent attention has been given to animal feeding and its impact on human nutrition. Animal feeding is essential for meeting human dietary needs, making it a subject of significant interest and investigation. This review seeks to outline the current understanding of this disciplinary [...] Read more.
Recent attention has been given to animal feeding and its impact on human nutrition. Animal feeding is essential for meeting human dietary needs, making it a subject of significant interest and investigation. This review seeks to outline the current understanding of this disciplinary area, with a focus on key research areas and their potential implications. The initial part of the paper discusses the importance of animal feed resources and recognizes their crucial role in guaranteeing sufficient nutrition for both humans and animals. Furthermore, we analyzed the categorization of animal feeds based on the guidelines established by the National Research Council. This approach offers a valuable structure for comprehending and classifying diverse types of animal feed. Through an examination of this classification, we gain an understanding of the composition and nutritional content of various feedstuffs. We discuss the major categories of metabolites found in animal feed and their impact on animal nutrition, as well as their potential health advantages for humans. Flavonoids, polyphenols, tannins, terpenoids, vitamins, antioxidants, alkaloids, and essential oils are the primary focus of the examination. Moreover, we analyzed their possible transference into animal products, and later we observed their occurrence in foods from animal sources. Finally, we discuss their potential to promote human health. This review offers an understanding of the connections among the major metabolites found in feedstuffs, their occurrence in animal products, and their possible impact on the health of both animals and humans. Full article
(This article belongs to the Special Issue Bioactive Compounds in Animal Nutrition Resources and Animal By-Products)
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13 pages, 2717 KiB  
Article
A Preliminary Study on the Whole-Plant Regulations of the Shrub Campylotropis polyantha in Response to Hostile Dryland Conditions
by Hua Zhang, Xue Jiang, Lijun Zhu, Lei Liu, Zhengqiao Liao and Baoguo Du
Metabolites 2024, 14(9), 495; https://doi.org/10.3390/metabo14090495 - 13 Sep 2024
Viewed by 412
Abstract
Drylands cover more than 40% of global land surface and will continue to expand by 10% at the end of this century. Understanding the resistance mechanisms of native species is of particular importance for vegetation restoration and management in drylands. In the present [...] Read more.
Drylands cover more than 40% of global land surface and will continue to expand by 10% at the end of this century. Understanding the resistance mechanisms of native species is of particular importance for vegetation restoration and management in drylands. In the present study, metabolome of a dominant shrub Campylotropis polyantha in a dry-hot valley were investigated. Compared to plants grown at the wetter site, C. polyantha tended to slow down carbon (C) assimilation to prevent water loss concurrent with low foliar reactive oxygen species and sugar concentrations at the drier and hotter site. Nitrogen (N) assimilation and turn over were stimulated under stressful conditions and higher leaf N content was kept at the expense of root N pools. At the drier site, roots contained more water but less N compounds derived from the citric acid cycle. The site had little effect on metabolites partitioning between leaves and roots. Generally, roots contained more C but less N. Aromatic compounds were differently impacted by site conditions. The present study, for the first time, uncovers the apparent metabolic adaptations of C. polyantha to hostile dryland conditions. However, due to the limited number of samples, we are cautious about drawing general conclusions regarding the resistance mechanisms. Further studies with a broader spatial range and larger time scale are therefore recommended to provide more robust information for vegetation restoration and management in dryland areas under a changing climate. Full article
(This article belongs to the Special Issue Metabolic Responses of Plants to Abiotic Stress)
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18 pages, 10847 KiB  
Article
Organic Trace Minerals Enhance the Gut Health of British Shorthair Cats by Regulating the Structure of Intestinal Microbiota
by Yingyue Cui, Mingrui Zhang, Haotian Wang, Tong Yu, Anxuan Zhang, Gang Lin, Yuhan Guo and Yi Wu
Metabolites 2024, 14(9), 494; https://doi.org/10.3390/metabo14090494 - 11 Sep 2024
Viewed by 630
Abstract
Trace minerals are essential for biological processes, including enzyme function, immune response, and hormone synthesis. The study assessed the effects of different dietary trace minerals on the gut health, microbiota composition, and immune function of cats. Eighteen adult British Shorthair cats were divided [...] Read more.
Trace minerals are essential for biological processes, including enzyme function, immune response, and hormone synthesis. The study assessed the effects of different dietary trace minerals on the gut health, microbiota composition, and immune function of cats. Eighteen adult British Shorthair cats were divided into three groups receiving inorganic trace minerals (ITM), a 50/50 mix of inorganic and organic trace minerals (ITM + OTM), or organic trace minerals (OTM) for 28 days. The OTM showed enhanced immune capacities, reduced intestinal barrier function, and lower inflammation condition. The OTM altered gut microbiota diversity, with a lower Simpson index and higher Shannon index (p < 0.05). Specifically, the abundance of Bacteroidota, Lachnospiraceae, and Prevotella in the OTM group were higher than the ITM group (p < 0.05). Metabolomic analysis identified 504 differential metabolites between the OTM and ITM groups (p < 0.05, VIP-pred-OPLS-DA > 1), affecting pathways related to steroid hormone biosynthesis and glycerophospholipid metabolism (p < 0.05, VIP-pred-OPLS-DA > 2). Additionally, there was a significant correlation between intestinal microbiota and differential metabolites. To conclude, dietary OTM can modulate the gut metabolite and microbiota composition, enhance immune and intestinal barrier function, and mitigate inflammation in cats, highlighting the benefit of using OTM in feline diet to promote the intestinal and overall health. Full article
(This article belongs to the Topic Research on Companion Animal Nutrition)
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11 pages, 4346 KiB  
Article
Utility of an Untargeted Metabolomics Approach Using a 2D GC-GC-MS Platform to Distinguish Relapsing and Progressive Multiple Sclerosis
by Indrani Datta, Insha Zahoor, Nasar Ata, Faraz Rashid, Mirela Cerghet, Ramandeep Rattan, Laila M. Poisson and Shailendra Giri
Metabolites 2024, 14(9), 493; https://doi.org/10.3390/metabo14090493 - 11 Sep 2024
Viewed by 447
Abstract
Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease of the central nervous system (CNS) in young adults and results in progressive neurological defects. The relapsing-remitting phenotype (RRMS) is the most common disease course in MS, which ultimately progresses to secondary progressive [...] Read more.
Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease of the central nervous system (CNS) in young adults and results in progressive neurological defects. The relapsing-remitting phenotype (RRMS) is the most common disease course in MS, which ultimately progresses to secondary progressive MS (SPMS), while primary progressive MS (PPMS) is a type of MS that worsens gradually over time without remissions. There is a gap in knowledge regarding whether the relapsing form can be distinguished from the progressive course, or healthy subjects (HS) based on an altered serum metabolite profile. In this study, we performed global untargeted metabolomics with the 2D GC-GC-MS platform to identify altered metabolites between RRMS, PPMS, and HS. We profiled 235 metabolites in the serum of patients with RRMS (n = 41), PPMS (n = 31), and HS (n = 91). A comparison of RRMS and HS patients revealed 22 significantly altered metabolites at p < 0.05 (false-discovery rate [FDR] = 0.3). The PPMS and HS comparisons revealed 28 altered metabolites at p < 0.05 (FDR = 0.2). Pathway analysis using MetaboAnalyst revealed enrichment of four metabolic pathways in both RRMS and PPMS (hypergeometric test p < 0.05): (1) galactose metabolism; (2) amino sugar and nucleotide sugar metabolism; (3) phenylalanine, tyrosine, and tryptophan biosynthesis; and (4) aminoacyl-tRNA biosynthesis. The Qiagen IPA enrichment test identified the sulfatase 2 (SULF2) (p = 0.0033) and integrin subunit beta 1 binding protein 1 (ITGB1BP1) (p = 0.0067) genes as upstream regulators of altered metabolites in the RRMS vs. HS groups. However, in the PPMS vs. HS comparison, valine was enriched in the neurodegeneration of brain cells (p = 0.05), and heptadecanoic acid, alpha-ketoisocaproic acid, and glycerol participated in inflammation in the CNS (p = 0.03). Overall, our study suggests that RRMS and PPMS may contribute metabolic fingerprints in the form of unique altered metabolites for discriminating MS disease from HS, with the potential for constructing a metabolite panel for progressive autoimmune diseases such as MS. Full article
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12 pages, 3121 KiB  
Article
Application of Eight Machine Learning Algorithms in the Establishment of Infertility and Pregnancy Diagnostic Models: A Comprehensive Analysis of Amino Acid and Carnitine Metabolism
by Rui Zhang, Lei Zhou, Xiaoyan Hao, Liu Yang, Li Ding, Ruiqing Xing, Juanjuan Hu, Fengjuan Wang, Xiaonan Zhai, Yuanbing Guo, Zheng Cai, Jiawei Gao, Jun Yang and Jiayun Liu
Metabolites 2024, 14(9), 492; https://doi.org/10.3390/metabo14090492 - 10 Sep 2024
Viewed by 481
Abstract
To explore the effects of altered amino acids (AAs) and the carnitine metabolism in non-pregnant women with infertility (NPWI), pregnant women without infertility (PWI) and infertility-treated pregnant women (ITPW) compared with non-pregnant women (NPW, control), and develop more efficient models for the diagnosis [...] Read more.
To explore the effects of altered amino acids (AAs) and the carnitine metabolism in non-pregnant women with infertility (NPWI), pregnant women without infertility (PWI) and infertility-treated pregnant women (ITPW) compared with non-pregnant women (NPW, control), and develop more efficient models for the diagnosis of infertility and pregnancy, 496 samples were evaluated for levels of 21 AAs and 55 carnitines using targeted high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Three methods were used to screen the biomarkers for modeling, with eight algorithms used to build and validate the model. The ROC, sensitivity, specificity, and accuracy of the infertility diagnosis training model were higher than 0.956, 82.89, 66.64, and 82.57%, respectively, whereas those of the validated model were higher than 0.896, 77.67, 69.72, and 83.38%, respectively. The ROC, sensitivity, specificity, and accuracy of the pregnancy diagnosis training model were >0.994, 96.23, 97.79, and 97.69%, respectively, whereas those of the validated model were >0.572, 96.39, 93.03, and 94.71%, respectively. Our findings indicate that pregnancy may alter the AA and carnitine metabolism in women with infertility to match the internal environment of PWI. The developed model demonstrated good performance and high sensitivity for facilitating infertility and pregnancy diagnosis. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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16 pages, 909 KiB  
Article
Sarcosine, Trigonelline and Phenylalanine as Urinary Metabolites Related to Visceral Fat in Overweight and Obesity
by Aline Maria Cavalcante Gurgel, Aline Lidiane Batista, Diogo Manuel Lopes de Paiva Cavalcanti, Alviclér Magalhães and Denise Engelbrecht Zantut-Wittmann
Metabolites 2024, 14(9), 491; https://doi.org/10.3390/metabo14090491 - 10 Sep 2024
Viewed by 503
Abstract
The objective of the present study is to analyze the urinary metabolome profile of patients with obesity and overweight and relate it to different obesity profiles. This is a prospective, cross-sectional study in which patients with a body mass index (BMI) ≥25 kg/m [...] Read more.
The objective of the present study is to analyze the urinary metabolome profile of patients with obesity and overweight and relate it to different obesity profiles. This is a prospective, cross-sectional study in which patients with a body mass index (BMI) ≥25 kg/m were selected. Anthropometric data were assessed by physical examination and body composition was obtained by bioimpedance (basal metabolic rate, body fat percentile, skeletal muscle mass, gross fat mass and visceral fat). Urine was collected for metabolomic analysis. Patients were classified according to abdominal circumference measurements between 81 and 93, 94 and 104, and >104 cm; visceral fat up to 16 kilos and less than; and fat percentiles of <36%, 36–46% and >46%. Spectral alignment of urinary metabolite signals and bioinformatic analysis were carried out to select the metabolites that stood out. NMR spectrometry was used to detect and quantify the main urinary metabolites and to compare the groups. Seventy-five patients were included, with a mean age of 38.3 years, and 72% females. The urinary metabolomic profile showed no differences in BMI, abdominal circumference and percentage of body fat. Higher concentrations of trigonelline (p = 0.0488), sarcosine (p = 0.0350) and phenylalanine (p = 0.0488) were associated with patients with visceral fat over 16 kg. The cutoff points obtained by the ROC curves were able to accurately differentiate between patients according to the amount of visceral fat: sarcosine 0.043 mg/mL; trigonelline 0.068 mg/mL and phenylalanine 0.204 mg/mL. In conclusion, higher visceral fat was associated with urinary levels of metabolites such as sarcosine, related to insulin resistance; trigonelline, related to muscle mass and strength; and phenylalanine, related to glucose metabolism and abdominal fat. Trigonelline, sarcosine and phenylalanine play significant roles in regulating energy balance and metabolic pathways essential for controlling obesity. Our findings could represent an interesting option for the non-invasive estimation of visceral fat through biomarkers related to alterations in metabolic pathways involved in the pathophysiology of obesity. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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27 pages, 1289 KiB  
Review
Natural Products and Derivatives Targeting Metabolic Reprogramming in Colorectal Cancer: A Comprehensive Review
by Mengyu Wang, Liqun Qu, Xinying Du, Peng Song, Jerome P. L. Ng, Vincent Kam Wai Wong, Betty Yuen Kwan Law and Xianjun Fu
Metabolites 2024, 14(9), 490; https://doi.org/10.3390/metabo14090490 - 9 Sep 2024
Viewed by 594
Abstract
Metabolic reprogramming is a critical pathogenesis of colorectal cancer (CRC), referring to metabolic disorders that cancer cells make in response to the stimulating pressure. Metabolic reprogramming induces changes in genetic material and promotes CRC progression and has been proven to be an efficient [...] Read more.
Metabolic reprogramming is a critical pathogenesis of colorectal cancer (CRC), referring to metabolic disorders that cancer cells make in response to the stimulating pressure. Metabolic reprogramming induces changes in genetic material and promotes CRC progression and has been proven to be an efficient target of CRC. As natural products have garnered interest due to notable pharmacological effects and potential in counteracting chemoresistance, an increasing body of research is delving into the impact of these natural products on the metabolic reprogramming associated with CRC. In this review, we collected published data from the Web of Science and PubMed, covering the period from January 1980 to October 2023. This article focuses on five central facets of metabolic alterations in cancer cells, glucose metabolism, mitochondrial oxidative phosphorylation (OXPHOS), amino acid metabolism, fatty acid synthesis, and nucleotide metabolism, to provide an overview of recent advancements in natural product interventions targeting metabolic reprogramming in CRC. Our analysis underscores the potential of natural products in disrupting the metabolic pathways of CRC, suggesting promising therapeutic targets for CRC and expanding treatment options for metabolic-associated ailments. Full article
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13 pages, 4384 KiB  
Article
Association of Whole Blood Amino Acid and Acylcarnitine Metabolome with Anthropometry and IGF-I Serum Levels in Healthy Children and Adolescents in Germany
by Ricky Jensch, Ronny Baber, Antje Körner, Wieland Kiess, Uta Ceglarek, Antje Garten and Mandy Vogel
Metabolites 2024, 14(9), 489; https://doi.org/10.3390/metabo14090489 - 9 Sep 2024
Viewed by 437
Abstract
Background: Physiological changes of blood amino acids and acylcarnitines during healthy child development are poorly studied. The LIFE (Leipziger Forschungszentrum für Zivilisationserkrankungen) Child study offers a platform with a large cohort of healthy children to investigate these dynamics. We aimed to assess the [...] Read more.
Background: Physiological changes of blood amino acids and acylcarnitines during healthy child development are poorly studied. The LIFE (Leipziger Forschungszentrum für Zivilisationserkrankungen) Child study offers a platform with a large cohort of healthy children to investigate these dynamics. We aimed to assess the intra-person variability of 28 blood metabolites and their associations with anthropometric parameters related to growth and excess body fat. Methods: Concentrations of 22 amino acids (AA), 5 acylcarnitines (AC) and free carnitine of 2213 children aged between 3 months and 19 years were analyzed using liquid chromatography/tandem mass spectrometry. Values were transformed into standard deviation scores (SDS) to account for sex- and age-related variations. The stability of metabolites was assessed through the coefficient of determination. Associations with parameters for body composition and insulin-like growth factor-I (IGF-I) SDS were determined by the Pearson correlation and linear regression. Results: Our research revealed substantial within-person variation in metabolite concentrations during childhood and adolescence. Most metabolites showed a positive correlation with body composition parameters, with a notable influence of sex, pubertal status and weight group. Glycine exhibited negative associations with parameters of body fat distribution, especially in normal weight girls, overweight/obese boys and during puberty. Conclusion: Blood AA and AC measurements may contribute to elucidating pathogenesis pathways of adiposity-related comorbidities, but the specific timings and conditions of development during childhood and adolescence need to be taken into consideration. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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13 pages, 3832 KiB  
Article
Thioredoxin-Interacting Protein’s Role in NLRP3 Activation and Osteoarthritis Pathogenesis by Pyroptosis Pathway: In Vivo Study
by Ruba Altahla and Xu Tao
Metabolites 2024, 14(9), 488; https://doi.org/10.3390/metabo14090488 - 7 Sep 2024
Viewed by 523
Abstract
Thioredoxin-interacting protein (TXNIP) has been involved in oxidative stress and activation of the NOD-like receptor protein-3 (NLRP3) inflammasome, directly linking it to the pyroptosis pathway. Furthermore, pyroptosis may contribute to the inflammatory process in osteoarthritis (OA). The purpose of this study was to [...] Read more.
Thioredoxin-interacting protein (TXNIP) has been involved in oxidative stress and activation of the NOD-like receptor protein-3 (NLRP3) inflammasome, directly linking it to the pyroptosis pathway. Furthermore, pyroptosis may contribute to the inflammatory process in osteoarthritis (OA). The purpose of this study was to investigate the role of TXNIP in activating the NLRP3 inflammasome through the pyroptosis pathway in an OA rat model. Destabilization of the medial meniscus (DMM) was induced in the OA model with intra-articular injections of adeno-associated virus (AAV) overexpressing (OE) or knocking down (KD) TXNIP. A total of 48 healthy rats were randomly divided into six groups (N = 8 each). During the experiment, the rats’ weights, mechanical pain thresholds, and thermal pain thresholds were measured weekly. Morphology staining, micro-CT, 3D imaging, and immunofluorescence (IF) staining were used to measure the expression level of TXNIP, and ELISA techniques were employed. OE-TXNIP-AAV in DMM rats aggravated cartilage destruction and subchondral bone loss, whereas KD-TXNIP slowed the progression of OA. The histological results showed that DMM modeling and OE-TXNIP-AAV intra-articular injection caused joint structure destruction, decreased anabolic protein expression, and increased catabolic protein expression and pyroptosis markers. Conversely, KD-TXNIP-AAV slowed joint degeneration. OE-TXNIP-AVV worsened OA by accelerating joint degeneration and damage, while KD-TXNIP-AAV treatment had a protective effect. Full article
(This article belongs to the Section Cell Metabolism)
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11 pages, 1507 KiB  
Article
The Endogenous Inhibitor of CETP, apoC1, Remains Ineffective In Vivo after Correction of Hyperglycemia in People with Type 1 Diabetes
by Alexia Rouland, Thomas Gautier, Damien Denimal, Laurence Duvillard, Isabelle Simoneau, David Rageot, Bruno Vergès and Benjamin Bouillet
Metabolites 2024, 14(9), 487; https://doi.org/10.3390/metabo14090487 - 7 Sep 2024
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Abstract
ApolipoproteinC1 (apoC1) is the main physiological inhibitor of the cholesterol ester transfer protein (CETP). Increased CETP activity is associated with macrovascular complications in patients with type 1 diabetes (T1D). ApoC1 has lost its ability to inhibit CETP in patients with T1D, and in [...] Read more.
ApolipoproteinC1 (apoC1) is the main physiological inhibitor of the cholesterol ester transfer protein (CETP). Increased CETP activity is associated with macrovascular complications in patients with type 1 diabetes (T1D). ApoC1 has lost its ability to inhibit CETP in patients with T1D, and in vitro glycation of apoC1 increases CETP activity, suggesting that hyperglycemia could be a factor implicated in the loss of the inhibitory effect of apoC1 on CETP. Thus, we aimed to see whether improvement of glycemic control might restore apoC1 inhibitory effect on CETP. We studied 98 patients with T1D and HbA1c > 9% at baseline and 3 months after improvement of glycemic control by a medical intervention (insulin introduction or changes in multi-injection therapy or pump therapy introduction/therapeutic education for all patients). CETP activity was assessed by a radioactive method and plasma apoC1 levels were measured by ELISA. The different isoforms of apoC1 were determined by mass spectrometry. CETP activity was not significantly modified after improvement of glycemic control, despite a significant reduction in mean HbA1c (8.7 ± 1.7 vs. 10.8 ± 2, p < 0.0001). No association between plasma apoC1 and CETP activity was observed in patients with T1D at baseline, nor at 3 months, even in the subgroup of patients with optimal control (3-month HbA1c < 7%). We did not find any glycated form of apoC1 using mass spectrometry in people with T1D. Hyperglycemia in vivo does not seem to be a major factor implicated in the loss of apoC1 ability to inhibit CETP activity observed in T1D. Other factors, such as qualitative abnormalities of lipoproteins, could be involved. Our data emphasize the fact that hyperglycemia is not the only factor involved in lipid abnormalities and macrovascular complications in T1D. Clinical trial reg. no. NCT02816099 ClinicalTrials.gov. Full article
(This article belongs to the Section Lipid Metabolism)
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19 pages, 2507 KiB  
Article
Selenium, Zinc, and Plasma Total Antioxidant Status and the Risk of Colorectal Adenoma and Cancer
by Miłosława Zowczak-Drabarczyk, Jacek Białecki, Teresa Grzelak, Mikołaj Michalik and Dorota Formanowicz
Metabolites 2024, 14(9), 486; https://doi.org/10.3390/metabo14090486 - 6 Sep 2024
Viewed by 468
Abstract
Selenium (Se), zinc (Zn), and copper (Cu) are known to be involved in carcinogenesis and participate in the defence against reactive oxygen species (ROS). This study aimed to evaluate the clinical utility of serum Se, Zn, and Cu concentrations and plasma total antioxidant [...] Read more.
Selenium (Se), zinc (Zn), and copper (Cu) are known to be involved in carcinogenesis and participate in the defence against reactive oxygen species (ROS). This study aimed to evaluate the clinical utility of serum Se, Zn, and Cu concentrations and plasma total antioxidant status (TAS) in the diagnosis of colorectal cancer (CRC) and colorectal adenoma (CRA) in a population of low Se and borderline Zn status. Based on clinical examination and colonoscopy/histopathology, the patients (n = 79) were divided into three groups: colorectal cancer (n = 30), colorectal adenoma (n = 19), and controls (CONTROL, n = 30). The serum Se concentration was lower in the CRC group than in the CRA group (by 9.1%, p < 0.0001) and the CONTROL group (by 7.9%, p < 0.0001). In turn, the serum Zn concentration was decreased in the CRA group (by 17.9%, p = 0.019) when compared to the CONTROL group. Plasma TAS was lower in the CRC group (by 27.8%, p = 0.017) than in the CONTROL group. In turn, the serum Zn concentration was decreased in the CRA group when compared to the CONTROL group. Plasma TAS was lower in the CRC group than in the CONTROL group. ROC (receiver operating characteristic) curve analysis revealed that the Se level was of the highest diagnostic utility for the discrimination of the CRC group from both the CRA group (area under ROC curve (AUC) 0.958, sensitivity 84.21%, specificity 100%) and the CONTROL group (AUC 0.873, sensitivity 100%, specificity 66.67%). The Zn and TAS levels were significantly accurate in the differentiation between the groups. An individualised risk of colorectal adenoma and cancer approach could comprise Se, Zn, and TAS assays in the population. Full article
(This article belongs to the Special Issue Inflammation and Oxidative Stress in Age-Related Metabolic Changes and Disorders)
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15 pages, 875 KiB  
Article
The Impact of Metabolic Syndrome on Heart Failure in Young Korean Population: A Nationwide Study
by Tae-Eun Kim, Do Young Kim, Hyeongsu Kim, Jidong Sung, Duk-Kyung Kim, Myoung-Soon Lee, Seong Woo Han, Hyun-Joong Kim, Hyun Kyun Ki, Sung Hea Kim and Kyu-Hyung Ryu
Metabolites 2024, 14(9), 485; https://doi.org/10.3390/metabo14090485 - 4 Sep 2024
Viewed by 650
Abstract
Limited data are available regarding the effect of metabolic syndrome on heart failure (HF) development in young individuals. Utilizing data from the Korean National Health Insurance Service, we included a total of 1,958,284 subjects in their 40s who underwent health screening between January [...] Read more.
Limited data are available regarding the effect of metabolic syndrome on heart failure (HF) development in young individuals. Utilizing data from the Korean National Health Insurance Service, we included a total of 1,958,284 subjects in their 40s who underwent health screening between January 2009 and December 2009 in Korea. Subjects were classified into three groups: normal, pre-metabolic syndrome (Pre-MetS), and metabolic syndrome (MetS). MetS was identified in 10.58% of males and 5.21% of females. The hazard ratio for HF in subjects with MetS was 1.968 (95% CI: 1.526–2.539) for males and 2.398 (95% CI: 1.466–3.923) for females. For those with Pre-MetS, the hazard ratio was 1.607 (95% CI: 1.293–1.997) in males and 1.893 (95% CI: 1.43–2.505) in females. Additionally, acute myocardial infarction and low hemoglobin levels were identified as significant risk factors for HF in both genders. MetS approximately doubled the risk of developing HF in individuals in their 40s. Pre-MetS was also a significant risk factor for HF in this population. Full article
(This article belongs to the Special Issue Association between Cardiovascular Events and Metabolic Syndromes)
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