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1
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Ferreira H, Duarte D, Carneiro TJ, Costa C, Barbosa JC, Rodrigues JE, Alves P, Vasconcelos M, Pinto E, Gomes A, Gil AM. Impact of a legumes diet on the human gut microbiome articulated with fecal and plasma metabolomes: A pilot study. Clin Nutr ESPEN 2024; 63:332-345. [PMID: 38964655 DOI: 10.1016/j.clnesp.2024.06.051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 06/12/2024] [Accepted: 06/27/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND & AIMS Legumes intake is known to be associated with several health benefits the origins of which is still a matter of debate. This paper addresses a pilot small cohort to probe for metabolic aspects of the interplay between legumes intake, human metabolism and gut microbiota. METHODS Untargeted nuclear magnetic resonance (NMR) metabolomics of blood plasma and fecal extracts was carried out, in tandem with qPCR analysis of feces, to assess the impact of an 8-week pilot legumes diet intervention on the fecal and plasma metabolomes and gut microbiota of 19 subjects. RESULTS While the high inter-individual variability hindered the detection of statistically significant changes in the gut microbiome, increased fecal glucose and decreased threonine levels were noted. Correlation analysis between the microbiome and fecal metabolome lead to putative hypotheses regarding the metabolic activities of prevalent bacteria groups (Clostridium leptum subgroup, Roseburia spp., and Faecalibacterium prausnitzii). These included elevated fecal glucose as a preferential energy source, the involvement of valerate/isovalerate and reduced protein degradation in gut microbiota. Plasma metabolomics advanced mannose and betaine as potential markers of legume intake and unveiled a decrease in formate and ketone bodies, the latter suggesting improved energy utilization through legume carbohydrates. Amino acid metabolism was also apparently affected, as suggested by lowered urea, histidine and threonine levels. CONCLUSIONS Despite the high inter-individual gut microbiome variability characterizing the small cohort addressed, combination of microbiological measurements and untargeted metabolomics unveiled several metabolic effects putatively related to legumes intake. If confirmed in larger cohorts, our findings will support the inclusion of legumes in diets and contribute valuable new insight into the origins of associated health benefits.
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Affiliation(s)
- Helena Ferreira
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Porto, Portugal; Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal
| | - Daniela Duarte
- Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal
| | - Tatiana J Carneiro
- Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal
| | - Célia Costa
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Porto, Portugal
| | - Joana C Barbosa
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Porto, Portugal
| | - João E Rodrigues
- Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal
| | - Paulo Alves
- Universidade Católica Portuguesa, CIIS - Centro de Investigação Interdisciplinar em Saúde, Escola Enfermagem (Porto), Portugal
| | - Marta Vasconcelos
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Porto, Portugal
| | - Elisabete Pinto
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Porto, Portugal; EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal
| | - Ana Gomes
- Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Porto, Portugal
| | - Ana M Gil
- Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal.
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Chen Y, Cheng S, Dai J, Wang L, Xu Y, Peng X, Xie X, Peng C. Molecular mechanisms and applications of tea polyphenols: A narrative review. J Food Biochem 2021; 45:e13910. [PMID: 34426979 DOI: 10.1111/jfbc.13910] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/29/2021] [Accepted: 08/09/2021] [Indexed: 12/12/2022]
Abstract
Tea is a worldwide popular drink with high nutritional and medicinal values as it is rich in nutrients, such as polyphenols, amino acids, vitamins, glycosides, and so on. Among them, tea polyphenols (TPs) are the current research hotspot. TPs are known to have multiple biological activities such as anti-oxidation, anti-tumor, anti-inflammation, anti-bacteria, lowering lipid, and liver protection. By reviewing a large number of literatures, we explained the mechanism of TPs exerting biological activity and a wide range of applications. We also discussed the deficiencies and development potential of TPs, in order to provide theoretical reference and scientific basis for the subsequent development and utilization of TPs. PRACTICAL APPLICATIONS: We summarized the bioactivity mechanisms of TPs in anti-tumor, anti-oxidation, antibacterial, anti-inflammatory, lipid-lowering, and liver protection, focused on its application fields in food and medicine, and discussed the deficiency and development potential of current research on TPs, so as to provide a certain convenient way for scholars studying TPs. It is expected to contribute to the subsequent discovery of biological activity and the broadening of the field of TPs.
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Affiliation(s)
- Yan Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Si Cheng
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jiangang Dai
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Liang Wang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yun Xu
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaoyu Peng
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaofang Xie
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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3
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Intestinal Microbial Metabolites in Ankylosing Spondylitis. J Clin Med 2021; 10:jcm10153354. [PMID: 34362137 PMCID: PMC8347740 DOI: 10.3390/jcm10153354] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/21/2021] [Accepted: 07/27/2021] [Indexed: 12/12/2022] Open
Abstract
Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by inflammation of axial joints and the pelvis. It is known that intestinal dysbiosis may exert direct pathogenic effects on gut homeostasis and may act as a triggering factor for the host innate immune system to activate and cause inflammation in extraintestinal sites in the so-called "gut-joint axis", contributing to AS pathogenesis. However, although the intestinal microbiota's influence on the clinical manifestation of AS is widely accepted, the mechanisms mediating the cross-talk between the intestinal lumen and the immune system are still not completely defined. Recent evidence suggests that the metabolism of microbial species may be a source of metabolites and small molecules participating in the complex network existing between bacteria and host cells. These findings may give inputs for further research of novel pharmacological targets and pave the way to applying dietary interventions to prevent the onset and ameliorate the clinical presentation of the disease. In this review, we discuss the role of some of the biological mediators of microbial origin, with a particular focus on short-chain fatty acids, tryptophan and vitamin B derivatives, and their role in barrier integrity and type 3 immunity in the context of AS.
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Tian B, Zhao J, Xie X, Chen T, Yin Y, Zhai R, Wang X, An W, Li J. Anthocyanins from the fruits of Lycium ruthenicum Murray improve high-fat diet-induced insulin resistance by ameliorating inflammation and oxidative stress in mice. Food Funct 2021; 12:3855-3871. [PMID: 33704297 DOI: 10.1039/d0fo02936j] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
A high-fat diet (HFD) promotes tissue inflammation, oxidative stress and insulin resistance (IR), thereby contributing to the development of obesity and diabetes. Anthocyanins from Lycium ruthenicum (AC) have demonstrated anti-obesity effects and modulated IR. To investigate the mechanism by which AC attenuates the adverse effects of consuming a HFD, C57BL/6J mice were fed a HFD supplemented with AC or a control diet without AC for 12 weeks. AC supplementation decreased the amount of weight gain, hepatic lipid, and sequentially improved dyslipidemia, inflammation, oxidative stress, and IR in HFD-fed mice. Molecular data revealed that AC inhibited hepatic inflammation by reducing TLR4/NF-κB/JNK in the liver tissues and ameliorated oxidative stress by activating the Nrf2/HO-1/NQO1 pathway. Thus, AC might activate IRS-1/AKT and prevent HFD-induced gluconeogenesis and IR by ameliorating inflammation and oxidative stress. Modulation of inflammation and oxidative stress with AC may represent a promising target for the treatment of IR and provide insight into the mechanism by which AC protects against obesity.
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Affiliation(s)
- Baoming Tian
- College of Food Science and Engineering, Northwest A&F University, Yangling, P. R. China. and Institute of Wolfberry Engineering Technology Research, Ningxia Academy of Agricultural and Forestry Sciences, Yinchuan, P. R. China. and National Wolfberry Engineering Research Center, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan, P. R. China
| | - Jianhua Zhao
- Institute of Wolfberry Engineering Technology Research, Ningxia Academy of Agricultural and Forestry Sciences, Yinchuan, P. R. China. and National Wolfberry Engineering Research Center, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan, P. R. China
| | - Xiaoqing Xie
- College of Food Science and Engineering, Northwest A&F University, Yangling, P. R. China.
| | - Tao Chen
- College of Food Science and Engineering, Northwest A&F University, Yangling, P. R. China.
| | - Yan Yin
- College of Food Science and Engineering, Northwest A&F University, Yangling, P. R. China.
| | - Ruohan Zhai
- College of Food Science and Engineering, Northwest A&F University, Yangling, P. R. China.
| | - Xinlei Wang
- College of Food Science and Engineering, Northwest A&F University, Yangling, P. R. China.
| | - Wei An
- Institute of Wolfberry Engineering Technology Research, Ningxia Academy of Agricultural and Forestry Sciences, Yinchuan, P. R. China. and National Wolfberry Engineering Research Center, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan, P. R. China
| | - Juxiu Li
- College of Food Science and Engineering, Northwest A&F University, Yangling, P. R. China.
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Puri BK, Kingston MC, Monro JA. Inverse relationship between human erythrocyte fructose-6-phosphate and short-chain fatty acid levels. Med Hypotheses 2018; 121:164-166. [PMID: 30396473 DOI: 10.1016/j.mehy.2018.10.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Accepted: 10/01/2018] [Indexed: 11/30/2022]
Abstract
In muscle cells, fructose is initially metabolised to fructose-6-phosphate. In the liver, fructose is metabolised to fructose-1-phosphate and thence to glyceraldehydes, which in turn can either enter glycogenolysis via pyruvate or gluconeogenesis via fructose-1,6-bisphosphate and fructose-6-phosphate. High levels of fructose-1-phosphate inhibit both glycogenolysis and gluconeogenesis. We hypothesised that, if systemically absorbed short-chain fatty acids constitute a major metabolic fate of unabsorbed dietary fructose, then levels of erythrocyte fructose-6-phosphate would be inversely correlated with plasma levels of short-chain fatty acids. The aim of this study was to test this hypothesis in respect of the three main short-chain fatty acids acetate, propionate and butyrate. Venous blood samples from 39 patients (16 male, 23 female, mean (standard error) age 42.4 (3.3) years) were analysed. Erythrocyte fructose-6-phosphate was measured using quantitative Fourier transform infrared spectrometry following gel electrophoresis, while plasma acetate, propionate and butyrate levels were measured using gas-liquid chromatography. The erythrocyte fructose-6-phosphate level was inversely correlated with the plasma acetate (r = -0.30, p = 0.06), propionate (r = -0.31, p = 0.05) and butyrate (r = -0.40, p = 0.01). These results support our hypothesis. The conversion of unabsorbed dietary fructose into short-chain fatty acids may represent a protective mechanism against the adverse effects of hypoglycaemia.
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Affiliation(s)
- B K Puri
- Department of Medicine, Imperial College London, UK.
| | - M C Kingston
- Breakspear Medical Group, Hemel Hempstead, Hertfordshire, UK
| | - J A Monro
- Breakspear Medical Group, Hemel Hempstead, Hertfordshire, UK
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Silva JCP, Mota M, Martins FO, Nogueira C, Gonçalves T, Carneiro T, Pinto J, Duarte D, Barros AS, Jones JG, Gil AM. Intestinal Microbial and Metabolic Profiling of Mice Fed with High-Glucose and High-Fructose Diets. J Proteome Res 2018; 17:2880-2891. [PMID: 29923728 DOI: 10.1021/acs.jproteome.8b00354] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease; however, the mechanisms through which glucose and fructose promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with diets with glucose (G) or fructose (F) as sole carbohydrates, and a third group was fed with a normal chow carbohydrate mixture (N). Fecal metabolites were profiled by nuclear magnetic resonance (NMR) and microbial composition by real-time polymerase chain reaction (qPCR). Although N, G and F mice exhibited similar weight gains (with slight slower gains for F) and glucose tolerance, multivariate analysis of NMR data indicated that F mice were separated from N and G, with decreased butyrate and glutamate and increased fructose, succinate, taurine, tyrosine, and xylose. The different sugar diets also resulted in distinct intestinal microbiota profiles. That associated with fructose seemed to hold more potential to induce host metabolic disturbances compared to glucose, mainly by promoting bile acid deconjugation and taurine release and compromising intestinal barrier integrity. This may reflect the noted nonquantitative intestinal fructose absorption hence increasing its availability for microbial metabolism, a subject for further investigation.
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Affiliation(s)
- João C P Silva
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal
| | - Marta Mota
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,Institute of Microbiology, Faculty of Medicine , University of Coimbra , Coimbra , Portugal
| | - Fátima O Martins
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,CEDOC, NOVA Medical School , Universidade NOVA de Lisboa , Rua Câmara Pestana, n°6, 6A, edifício II, piso 3 , 1150-082 Lisbon , Portugal
| | - Célia Nogueira
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,Institute of Microbiology, Faculty of Medicine , University of Coimbra , Coimbra , Portugal
| | - Teresa Gonçalves
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,Institute of Microbiology, Faculty of Medicine , University of Coimbra , Coimbra , Portugal
| | - Tatiana Carneiro
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal
| | - Joana Pinto
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal.,UCIBIO@REQUIMTE/Toxicological Laboratory, Biological Science Department, Faculty of Pharmacy , University of Porto , 4050-313 Porto , Portugal
| | - Daniela Duarte
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal
| | - António S Barros
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal.,Department of Cardiothoracic Surgery and Physiology, Faculty of Medicine , University of Porto , 4200-319 , Porto , Portugal
| | - John G Jones
- CNC - Centre for Neuroscience and Cell Biology , University of Coimbra , Coimbra , Portugal.,CEDOC, NOVA Medical School , Universidade NOVA de Lisboa , Rua Câmara Pestana, n°6, 6A, edifício II, piso 3 , 1150-082 Lisbon , Portugal.,APDP - Portuguese Diabetes Association , Lisbon , Portugal
| | - Ana M Gil
- CICECO-Aveiro Institute of Materials and Department of Chemistry , University of Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal
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Abstract
PURPOSE OF REVIEW The purpose of this review is to highlight recent evidence with respect to expression and metabolomic profiling in axial spondyloarthritis (axSpA) that included ankylosing spondylitis (AS). RECENT FINDINGS AxSpA is not only characterized by the strongest genetic contribution for any complex rheumatic disease but is also influenced by environmental and immunological factors. Large-scale association-based studies have identified over 100 genetic variants contributing to 30% of the genetic risk of ankylosing spondylitis. Recent studies in global expression and metabolomic profiling appear to highlight common themes despite differences in tissues, populations, techniques, and relative paucity of patients in many of these studies. Expression studies support a role for immunomodulation and bone remodeling in the pathogenesis and progression of axSpA/AS, while metabolomic studies implicate the importance of the intestinal microbial metabolism as well as fat and choline metabolic pathways in AS.
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Wu Y, Li W, Lu Y, Wu Q, Yang X. Stachyose combined with tea polyphenols mitigated metabolic disorders in high fructose diet-fed mice as studied by GC-MS metabolomics approach. CYTA - JOURNAL OF FOOD 2018. [DOI: 10.1080/19476337.2017.1420101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Yingmei Wu
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an, China
- The Chongqing Engineering Laboratory for Green Cultivation and Deep Processing of the Three Gorges Reservoir Area’s Medicinal Herbs, College of Biology and Food Engineering, Chongqing Three Gorges University, Chongqing, China
| | - Wenfeng Li
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an, China
- Key Laboratory of Chongqing Municipality for Protection and Utility of Unique Plant Resources in the Wulingshan Region, School of Life Science and Biotechnology, Yangtze Normal University, Chongqing, China
| | - Yalong Lu
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an, China
| | - Qiu Wu
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an, China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an, China
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9
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Schofield Z, Reed MAC, Newsome PN, Adams DH, Günther UL, Lalor PF. Changes in human hepatic metabolism in steatosis and cirrhosis. World J Gastroenterol 2017; 23:2685-2695. [PMID: 28487605 PMCID: PMC5403747 DOI: 10.3748/wjg.v23.i15.2685] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 01/11/2017] [Accepted: 03/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To understand the underlying metabolic changes in human liver disease we have applied nuclear magnetic resonance (NMR) metabolomics analysis to human liver tissue.
METHODS We have carried out pilot study using 1H-NMR to derive metabolomic signatures from human liver from patients with steatosis, nonalcoholic steatohepatitis (NASH) or alcohol-related liver damage (ARLD) to identify species that can predict outcome and discriminate between alcohol and metabolic-induced liver injuries.
RESULTS Changes in branched chain amino acid homeostasis, tricarboxylic acid cycle and purine biosynthesis intermediates along with betaine were associated with the development of cirrhosis in both ARLD and nonalcoholic fatty liver disease. Species such as propylene glycol and as yet unidentified moieties that allowed discrimination between NASH and ARLD samples were also detected using our approach.
CONCLUSION Our high throughput, non-destructive technique for multiple analyte quantification in human liver specimens has potential for identification of biomarkers with prognostic and diagnostic significance.
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10
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Wang W, Yang GJ, Zhang J, Chen C, Jia ZY, Li J, Xu WD. Plasma, urine and ligament tissue metabolite profiling reveals potential biomarkers of ankylosing spondylitis using NMR-based metabolic profiles. Arthritis Res Ther 2016; 18:244. [PMID: 27770826 PMCID: PMC5075188 DOI: 10.1186/s13075-016-1139-2] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Accepted: 09/27/2016] [Indexed: 12/31/2022] Open
Abstract
Background Ankylosing spondylitis (AS) is an autoimmune rheumatic disease mostly affecting the axial skeleton. Currently, anti-tumour necrosis factor α (anti-TNF-α) represents an effective treatment for AS that may delay the progression of the disease and alleviate the symptoms if the diagnosis can be made early. Unfortunately, effective diagnostic biomarkers for AS are still lacking; therefore, most patients with AS do not receive timely and effective treatment. The intent of this study was to determine several key metabolites as potential biomarkers of AS using metabolomic methods to facilitate the early diagnosis of AS. Methods First, we collected samples of plasma, urine, and ligament tissue around the hip joint from AS and control groups. The samples were examined by nuclear magnetic resonance spectrometry, and multivariate data analysis was performed to find metabolites that differed between the groups. Subsequently, according to the correlation coefficients, variable importance for the projection (VIP) and P values of the metabolites obtained in the multivariate data analysis, the most crucial metabolites were selected as potential biomarkers of AS. Finally, metabolic pathways involving the potential biomarkers were determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the metabolic pathway map was drawn. Results Forty-four patients with AS agreed to provide plasma and urine samples, and 30 provided ligament tissue samples. An equal number of volunteers were recruited for the control group. Multidimensional statistical analysis suggested significant differences between the patients with AS and control subjects, and the models exhibited good discrimination and predictive ability. A total of 20 different metabolites ultimately met the requirements for potential biomarkers. According to KEGG analysis, these marker metabolites were primarily related to fat metabolism, intestinal microbial metabolism, glucose metabolism and choline metabolism pathways, and they were also probably associated with immune regulation. Conclusions Our work demonstrates that the potential biomarkers that were identified appeared to have diagnostic value for AS and deserve to be further investigated. In addition, this work also suggests that the metabolomic profiling approach is a promising screening tool for the diagnosis of patients with AS.
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Affiliation(s)
- Wei Wang
- Department of Orthopedics, Chengdu Military General Hospital, Chengdu city, People's Republic of China
| | - Gen-Jin Yang
- School of Pharmacy, Second Military Medical University, Shanghai city, People's Republic of China
| | - Ju Zhang
- Department of Rheumatology, Changhai Hospital, Shanghai city, People's Republic of China
| | - Chen Chen
- Physical Examination Center, Changhai Hospital, Shanghai city, People's Republic of China
| | - Zhen-Yu Jia
- Department of Orthopedics, Changhai Hospital, Shanghai city, People's Republic of China
| | - Jia Li
- Department of Orthopedics, Changhai Hospital, Shanghai city, People's Republic of China
| | - Wei-Dong Xu
- Department of Orthopedics, Changhai Hospital, Shanghai city, People's Republic of China.
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11
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Tan Q, Wang W, Yang C, Zhang J, Sun K, Luo HC, Mai LF, Lao Y, Yan L, Ren M. α-ketoglutarate is associated with delayed wound healing in diabetes. Clin Endocrinol (Oxf) 2016; 85:54-61. [PMID: 26921880 DOI: 10.1111/cen.13047] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2015] [Revised: 01/06/2016] [Accepted: 02/21/2016] [Indexed: 01/13/2023]
Abstract
AIM A high level of matrix metalloproteinase 9 (MMP-9) is a predictor of poor wound healing in diabetic foot ulcers. In skin keratinocytes, site-specific DNA demethylation plays an important role in MMP-9 expression. Ten-eleven translocation enzyme 2 (TET2) protein, one member of TET family, could rely on α-ketoglutarate (α-KG) as cosubstrate to exhibit catalytic activity of DNA demethylation. Here, we aimed to explore the changes of α-KG and its relationship with MMP-9 and TET2 during diabetic wound healing. METHODS Seventy-one cases of patients with diabetic foot ulcers and 53 cases of nondiabetic ulcers were enrolled. Serum, urine and wound fluids were collected for measurement of α-KG levels and MMP-9 expression. Skin tissues were collected for the measurement of TET2 and MMP-9 expression. Clinical parameters were collected, and transcutaneous oxygen pressure (TcPO2) levels of feet were detected. RESULTS The levels of α-KG, TET2 and MMP-9 were significantly increased in diabetic wound compared with nondiabetic wound (P = 0·010, 0·016 and 0·025). There was a significant correlation between a low TcPO2 and a high α-KG level of wound fluids (r = -0·395, P = 0·002). Further analysis showed that α-KG concentration had a positive correlation with both haemoglobin A1c (HbA1C) and 2 h postprandial blood glucose (PBG) (r = 0·393, P = 0·005; r = 0·320, P = 0·025, respectively). CONCLUSIONS The levels of α-KG, TET2 and MMP-9 were significantly increased in diabetic wound compared with nondiabetic wound. Elevated α-KG was related to local hypoxia ischaemia status and systematic poor glycaemic control.
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Affiliation(s)
- Qin Tan
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Wei Wang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Chuan Yang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Jinglu Zhang
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Kan Sun
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Heng Cong Luo
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Li Fang Mai
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Yu Lao
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Li Yan
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Meng Ren
- Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
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12
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Su X, Wang N, Chen D, Li Y, Lu Y, Huan T, Xu W, Li L, Li L. Dansylation isotope labeling liquid chromatography mass spectrometry for parallel profiling of human urinary and fecal submetabolomes. Anal Chim Acta 2016; 903:100-9. [DOI: 10.1016/j.aca.2015.11.027] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Revised: 11/19/2015] [Accepted: 11/21/2015] [Indexed: 01/18/2023]
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Li W, Huang D, Gao A, Yang X. Stachyose increases absorption and hepatoprotective effect of tea polyphenols in high fructose-fed mice. Mol Nutr Food Res 2015; 60:502-10. [DOI: 10.1002/mnfr.201500547] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 10/28/2015] [Accepted: 11/03/2015] [Indexed: 01/22/2023]
Affiliation(s)
- Wenfeng Li
- College of Food Engineering and Nutritional Science; Shaanxi Normal University; Xi'an P. R. China
| | - Di Huang
- College of Food Engineering and Nutritional Science; Shaanxi Normal University; Xi'an P. R. China
| | - Anning Gao
- College of Food Engineering and Nutritional Science; Shaanxi Normal University; Xi'an P. R. China
| | - Xingbin Yang
- College of Food Engineering and Nutritional Science; Shaanxi Normal University; Xi'an P. R. China
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Wang P, Wang Q, Yang B, Zhao S, Kuang H. The Progress of Metabolomics Study in Traditional Chinese Medicine Research. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2015; 43:1281-310. [DOI: 10.1142/s0192415x15500731] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Traditional Chinese medicine (TCM) has played important roles in health protection and disease treatment for thousands of years in China and has gained the gradual acceptance of the international community. However, many intricate issues, which cannot be explained by traditional methods, still remain, thus, new ideas and technologies are needed. As an emerging system biology technology, the holistic view adopted by metabolomics is similar to that of TCM, which allows us to investigate TCM with complicated conditions and multiple factors in depth. In this paper, we tried to give a timely and comprehensive update about the methodology progression of metabolomics, as well as its applications, in different fields of TCM studies including quality control, processing, safety and efficacy evaluation. The herbs investigated by metabolomics were selected for detailed examination, including Anemarrhena asphodeloides Bunge, Atractylodes macrocephala Kidd, Pinellia ternate, etc.; furthermore, some valuable results have been obtained and summarized. In conclusion, although the study of metabolomics is at the early phase and requires further scrutiny and validation, it still provides bright prospects to dissect the synergistic action of multiple components from TCM. Overall, with the further development of analytical techniques, especially multi-analysis techniques, we expect that metabolomics will greatly promote TCM research and the establishment of international standards, which is beneficial to TCM modernization.
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Affiliation(s)
- Pengcheng Wang
- Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, P.R. China
| | - Qiuhong Wang
- Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, P.R. China
| | - Bingyou Yang
- Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, P.R. China
| | - Shan Zhao
- Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, P.R. China
| | - Haixue Kuang
- Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, P.R. China
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15
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Yang Y, Zheng L, Wang L, Wang S, Wang Y, Han Z. Effects of high fructose and salt feeding on systematic metabonome probed via (1) H NMR spectroscopy. MAGNETIC RESONANCE IN CHEMISTRY : MRC 2015; 53:295-303. [PMID: 25641270 DOI: 10.1002/mrc.4198] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Revised: 11/01/2014] [Accepted: 11/15/2014] [Indexed: 06/04/2023]
Abstract
Diets rich in high fructose and salt are increasingly popular in our daily life. A combination consumption of excessive fructose and salt can induce insulin resistance (IR) and hypertension (HT), which are major public health problems around the world. However, the effects of high fructose and salt on systematic metabonome remain unknown, which is very important for revealing the molecular mechanism of IR and HT induced by this dietary pattern. The metabolic profiling in urine, plasma, and fecal extracts from high fructose and salt-fed rats was investigated by use of (1) H nuclear magnetic resonance (NMR)-based metabonomics approach in this study. Multivariate analysis of NMR data showed the effects of high fructose and salt on the global metabonome. The metabolite analysis in urine and fecal extracts showed the time-dependent metabolic changes, which displayed metabonomic progression axes from normal to IR and HT status. The changes of 2-oxoglutarate, creatine and creatinine, citrate, hippurate, trimethylamine N-oxide (TMAO), and betaine in urine, together with gut microbiota disorder in feces, were observed at the preliminary formation stage of IR and HT (fourth week). At the severe stage (eighth week), the previously mentioned metabolic changes were aggravated, and the changes of lipid and choline metabolism in plasma suggested the increased risk of cardiovascular diseases. These findings provide an overview of biochemistry consequences of high fructose and salt feeding and comprehensive insights into the progression of systematic metabonome for IR and HT induced by this dietary pattern.
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Affiliation(s)
- Yongxia Yang
- School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, 510006, China
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16
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Gogna N, Krishna M, Oommen AM, Dorai K. Investigating correlations in the altered metabolic profiles of obese and diabetic subjects in a South Indian Asian population using an NMR-based metabolomic approach. MOLECULAR BIOSYSTEMS 2014; 11:595-606. [PMID: 25464928 DOI: 10.1039/c4mb00507d] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
It is well known that obesity/high body mass index (BMI) plays a key role in the evolution of insulin resistance and type-2 diabetes mellitus (T2DM). However, the exact mechanism underlying its contribution is still not fully understood. This work focuses on an NMR-based metabolomic investigation of the serum profiles of diabetic, obese South Indian Asian subjects. (1)H 1D and 2D NMR experiments were performed to profile the altered metabolic patterns of obese diabetic subjects and multivariate statistical methods were used to identify metabolites that contributed significantly to the differences in the samples of four different subject groups: diabetic and non-diabetic with low and high BMIs. Our analysis revealed that the T2DM-high BMI group has higher concentrations of saturated fatty acids, certain amino acids (leucine, isoleucine, lysine, proline, threonine, valine, glutamine, phenylalanine, histidine), lactic acid, 3-hydroxybutyric acid, choline, 3,7-dimethyluric acid, pantothenic acid, myoinositol, sorbitol, glycerol, and glucose, as compared to the non-diabetic-low BMI (control) group. Of these 19 identified significant metabolites, the levels of saturated fatty acids, lactate, valine, isoleucine, and phenylalanine are also higher in obese non-diabetic subjects as compared to control subjects, implying that this set of metabolites could be identified as potential biomarkers for the onset of diabetes in subjects with a high BMI. Our work validates the utility of NMR-based metabolomics in conjunction with multivariate statistical analysis to provide insights into the underlying metabolic pathways that are perturbed in diabetic subjects with a high BMI.
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Affiliation(s)
- Navdeep Gogna
- Indian Institute of Science Education & Research (IISER) Mohali, Knowledge City Sector 81, Mohali PO Manauli, 140306 Punjab, India.
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