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García Mansilla MJ, Rodríguez Sojo MJ, Lista AR, Ayala Mosqueda CV, Ruiz Malagón AJ, Gálvez J, Rodríguez Nogales A, Rodríguez Sánchez MJ. Exploring Gut Microbiota Imbalance in Irritable Bowel Syndrome: Potential Therapeutic Effects of Probiotics and Their Metabolites. Nutrients 2024; 17:155. [PMID: 39796588 PMCID: PMC11723002 DOI: 10.3390/nu17010155] [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: 12/04/2024] [Revised: 12/24/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Irritable bowel syndrome is a common functional gastrointestinal disorder characterized by recurrent abdominal discomfort, bloating, cramping, flatulence, and changes in bowel movements. The pathophysiology of IBS involves a complex interaction between motor, sensory, microbiological, immunological, and psychological factors. Diversity, stability, and metabolic activity of the gut microbiota are frequently altered in IBS, thus leading to a situation of gut dysbiosis. Therefore, the use of probiotics and probiotic-derived metabolites may be helpful in balancing the gut microbiota and alleviating irritable bowel syndrome symptoms. This review aimed to report and consolidate recent progress in understanding the role of gut dysbiosis in the pathophysiology of IBS, as well as the current studies that have focused on the use of probiotics and their metabolites, providing a foundation for their potential beneficial effects as a complementary and alternative therapeutic strategy for this condition due to the current absence of effective and safe treatments.
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Affiliation(s)
- María José García Mansilla
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
| | - María Jesús Rodríguez Sojo
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - Andrea Roxana Lista
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | | | - Antonio Jesús Ruiz Malagón
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29590 Málaga, Spain
| | - Julio Gálvez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
- CIBER de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Alba Rodríguez Nogales
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - María José Rodríguez Sánchez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
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Wang D, Song J, Wang J, Quan R. Serum metabolic alterations in chickens upon infectious bursal disease virus infection. BMC Vet Res 2024; 20:569. [PMID: 39696379 DOI: 10.1186/s12917-024-04402-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 11/22/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Infectious bursal disease virus (IBDV) is a highly contagious immunosuppressive virus of chickens. Chickens acquire infection by the oral route under natural conditions. Although the histological and pathological changes after IBDV infection are well described, the alterations in serum metabolome have not been reported. In this study, SPF chickens were infected with attenuated IBDV (atIBDV) strain LM and very virulent IBDV (vvIBDV) strain LX, respectively. On the seventh day after oral infection, serum samples of experimental chickens were identified using ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS). The serum metabolic profiles were analyzed by multivariate statistical methods. KEGG enrichment analysis was performed to evaluate the dysregulated biological pathways. RESULTS We identified 368 significantly altered metabolites in response to both atIBDV and vvIBDV infection. The metabolic disorder of amino acid and lipid was associated with IBDV infection, especially tryptophan, glycerophospholipid, lysine, and tyrosine metabolism. The differential metabolites enriched in the four metabolic pathways were PC(20:4(5Z,8Z,11Z,14Z)/18:0), PE(16:0/18:2(9Z,12Z)), PE(16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(18:0/20:4(5Z,8Z,11Z,14Z)), PE(18:0/20:4(8Z,11Z,14Z,17Z)), PE(18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PE(20:3(8Z,11Z,14Z)/16:0), PE(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:0), PE-NMe(20:5(5Z,8Z,11Z,14Z,17Z)/18:0), PS(20:3(5Z,8Z,11Z)/18:2(9Z,12Z)), 2-aminobenzoic acid, 4-(2-aminophenyl)-2,4-dioxobutanoic acid, N-acetylserotonin, 5-hydroxyindoleacetate, indole-3-acetaldehyde, indole-3-acetate, p-coumaric acid, L-tyrosine, homovanillin, and S-glutaryldihydrolipoamide. CONCLUSION The atIBDV and vvIBDV infection causes metabolic changes in chicken serum. The differential metabolites and dysregulated metabolic pathways reflect the host response to the IBDV infection.
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Affiliation(s)
- Dan Wang
- Beijing Key Laboratory for Prevention and mock of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road Haidian District, Beijing, 100097, China
| | - Jiangwei Song
- Beijing Key Laboratory for Prevention and mock of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road Haidian District, Beijing, 100097, China
| | - Jing Wang
- Beijing Key Laboratory for Prevention and mock of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road Haidian District, Beijing, 100097, China
| | - Rong Quan
- Beijing Key Laboratory for Prevention and mock of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road Haidian District, Beijing, 100097, China.
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Sun YW, Chen KM, Aliaga C, El-Bayoumy K. Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chrysene. Sci Rep 2024; 14:29517. [PMID: 39604478 PMCID: PMC11603290 DOI: 10.1038/s41598-024-80921-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 11/22/2024] [Indexed: 11/29/2024] Open
Abstract
The goal of this study is to develop a non-invasive approach for early detection of oral squamous cell carcinoma (OSCC) using our established mouse model that faithfully recapitulates the human disease. We present for the first time a comparative metabolomic profiling of saliva samples of the tobacco smoke constituent, dibenzo[def, p]pyrene, (DB[a, l]P) vs. DMSO (control)-treated mice using an established and highly sensitive LC-MS/MS approach. DB[a, l]P was administered by topical application into the mouse oral cavity (25 µmol, 3x week for 6 weeks) and saliva was collected 24 h after the last dose of carcinogen administration. Using an untargeted metabolomics approach (negative and positive modes), we found that DB[a, l]P differentially altered several metabolites known to be involved in the carcinogenesis process when compared to DMSO. Of particular significance, we found that DB[a, l]P significantly enriched the levels of phosphatidic acid, known to bind and activate mTORC which can enhance proliferation and promote carcinogenesis. Pathway enrichment analysis revealed that DB[a, l]P altered two major lipid metabolism pathways (phospholipid biosynthesis and glycerolipid metabolism). Collectively, our results using saliva as a safe and non-invasive approach, provide additional mechanistic insights on DB[a, l]P-induced OSCC and potential biomarkers for early detection and an opportunity for cancer interception via reprogramming lipid metabolism.
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Affiliation(s)
- Yuan-Wan Sun
- Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA
| | - Kun-Ming Chen
- Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA
| | - Cesar Aliaga
- Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA
| | - Karam El-Bayoumy
- Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.
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Wu Q, Liu K, Hou R, Wu X, Ruan X, Wang M, Sun Z, Meng L, Dai G, Li C, Wu J, Mu G. Integrative Lipid Pseudotargeted Metabolomics and Amino Acids Targeted Metabolomics Unravel the Therapeutic Mechanism of Rhizoma Paridis Saponins on Experimental Colitis of Damp-Heat Type. Drug Des Devel Ther 2024; 18:5087-5108. [PMID: 39554759 PMCID: PMC11568858 DOI: 10.2147/dddt.s476494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 10/14/2024] [Indexed: 11/19/2024] Open
Abstract
Purpose Inflammatory bowel disease (IBD) is a serious disease that affects the metabolism and inflammatory responses of human beings. From the perspective of traditional Chinese medicine, damp-heat syndrome is one of the main syndromes of IBD. Rhizoma Paridis, also known as the root of Paris polyphylla, a well-known herbal medicine used in China, is used to treat IBD with damp-heat syndrome (IBD-DH). However, uncertainty still exists regarding the underlying mechanisms and the impact of Rhizoma Paridis on IBD-DH. Methods The rats in the model (DAT) and medication administration (Rhizoma Paridis total saponins (RPTS) and Pennogenin (PN)) groups were given a high temperature and high humidity environment, high fat and high sugar diet combined with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish the model of experimental colitis of damp-heat type, and the normal control group (RNC) rats were given a normal diet at normal temperature and humidity. Damp-heat control group (DNC) was set with the same condition as DAT without TNBS. Hematoxylin-Eosin (HE) staining was used to observe the histopathological morphology of the rat colorectum. The expression of the metabolism-related genes (Phospholipase A2 (sPLA2, cPLA2), and phosphatidylethanolamine N-methyltransferase (PEMT)) was assessed by using real-time quantitative PCR analysis (RT-qPCR). And the levels of the metabolism-related proteins (sPLA2, cPLA2), S100A8/9, Arg-1, and cytokines were detected by enzyme-linked immunosorbent assay (ELISA) kit. To investigate lipids and amino acids which closely associated with the IBD and IBD-DH, lipid pseudotargeted metabolomics with UHPLC-TQ/MS analysis method, as well as targeted quantitative amino acid analysis were performed. Results Our data showed that RPTS (50 mg/kg) and PN (20 mg/kg) significantly ameliorated the severity of TNBS-induced colitis and downregulated the levels of circulating proinflammatory cytokines. Compared with RNC group, lipid pseudotargeted metabolomics demonstrated that glycerophospholipids, sphingolipids, carnitine, and glycerolipids were the four most perturbed lipid classes, and amino acids targeted metabolomics demonstrated that serine, N-acetylneuraminic acid, histidine, proline, taurine, and kynurenine changed significantly in DAT group . Correlation analyses showed tight associations between most of differential metabolites and proinflammatory cytokines. RPTS and PN both regulated glycerophospholipid metabolism and sphingolipid metabolism. However, both of them did not have a significant effect on amino acid modulation. RPTS and PN potentially regulated sPLA2, cPLA2, and PEMT. Conclusion These results showed that RPTS (50 mg/kg) and PN (20 mg/kg) effectively alleviated rats' colitis of damp-heat type, affected cytokines, and altered lipid metabolism without significant modulation on amino acid metabolism.
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Affiliation(s)
- Qi Wu
- Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China
| | - Kexin Liu
- Department of Gastroenterology, The 981th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Chengde, Hebei, 067000, People’s Republic of China
| | - Ruijuan Hou
- Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China
| | - Xingxing Wu
- Department of Gastroenterology, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, 450053, People’s Republic of China
| | - Xiaoyu Ruan
- Internal Medicine Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China
| | - Mao Wang
- Ethics Committee, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China
| | - Zhiting Sun
- Institute of Chinese Medicine of Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China
| | - Lingchang Meng
- Institute of Chinese Medicine of Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China
| | - Guoliang Dai
- Clinical Pharmacology Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China
| | - Changyin Li
- Clinical Pharmacology Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China
| | - Jing Wu
- Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China
- Institute of Chinese Medicine of Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China
| | - Genglin Mu
- Institute of Chinese Medicine of Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China
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Li W, Zhang Y, Wang Q, Wang Y, Fan Y, Shang E, Jiang S, Duan J. 6-Gingerol ameliorates ulcerative colitis by inhibiting ferroptosis based on the integrative analysis of plasma metabolomics and network pharmacology. Food Funct 2024; 15:6054-6067. [PMID: 38753306 DOI: 10.1039/d4fo00952e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
6-Gingerol (6-G), an active ingredient of ginger with anti-inflammation and anti-oxidation properties, can treat ulcerative colitis (UC). However, its underlying mechanism is still unclear. In this study, the pharmacodynamic evaluation of 6-G for treating UC was performed, and the mechanism of 6-G in ameliorating UC was excavated by plasma metabolomics and network pharmacology analysis, which was further validated by experimental and molecular docking. The results showed that 6-G could notably reduce diarrhea, weight loss, colonic pathological damage, and inflammation in UC mice. Plasma metabolomic results indicated that 6-G could regulate 19 differential metabolites, and its metabolic pathways mainly involved linoleic acid metabolism and arachidonic acid metabolism, which were closely associated with ferroptosis. Moreover, 60 potential targets for 6-G intervention on ferroptosis in UC were identified by network pharmacology, and enrichment analysis revealed that 6-G suppressed ferroptosis by modulating lipid peroxidation. Besides, the integration of metabolomics and network pharmacology showed that the regulation of 6-G on ferroptosis focused on 3 key targets, including ALOX5, ALOX15, and PTGS2. Further investigation indicated that 6-G significantly inhibited ferroptosis by decreasing iron load and malondialdehyde (MDA), and enhanced antioxidant capacity by reducing the content of glutathione disulfide (GSSG) and increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) in UC mice and RSL3-induced Caco-2 cells. Furthermore, molecular docking showed the high affinity of 6-G with the identified 3 key targets. Collectively, this study elucidated the potential of 6-G in ameliorating UC by inhibiting ferroptosis. The integrated strategy also provided a theoretical basis for 6-G in treating UC.
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Affiliation(s)
- Wenwen Li
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
| | - Yun Zhang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
| | - Quyi Wang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
| | - Yu Wang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
| | - Yuwen Fan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
| | - Erxin Shang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
| | - Shu Jiang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
| | - Jinao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, PR China.
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Oyebade AO, Taiwo GA, Idowu M, Sidney T, Queiroz O, Adesogan AT, Vyas D, Ogunade IM. Effects of direct-fed microbial supplement on ruminal and plasma metabolome of early-lactation dairy cows: Untargeted metabolomics approach. J Dairy Sci 2024; 107:2556-2571. [PMID: 37939839 DOI: 10.3168/jds.2023-23876] [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: 06/16/2023] [Accepted: 10/18/2023] [Indexed: 11/10/2023]
Abstract
We examined the effects of 2 multispecies direct-fed microbial (DFM) supplements on ruminal and plasma metabolome of early-lactation dairy cows using a high-coverage untargeted metabolomics approach. A total of 45 multiparous Holstein cows (41 ± 7 DIM) were enrolled for the 14-d pre-experimental and 91-d experimental period and were a subset from a lactation performance study, which used 114 cows. Cows were blocked using pre-experimental energy-corrected milk yield and randomly assigned within each block to 1 of 3 treatments: (1) corn silage-based diet with no DFM supplement (control; CON), (2) basal diet top-dressed with a mixture of Lactobacillus animalis and Propionibacterium freudenreichii at 3 × 109 cfu/d (PRO-A), or (3) basal diet top-dressed with a mixture of L. animalis, P. freudenreichii, Bacillus subtilis, and Bacillus licheniformis at 11.8 × 109 cfu/d (PRO-B). The basal diet was fed ad libitum daily as a TMR at 0600 and 1200 h for a duration of 91 d. Rumen fluid and blood samples were taken on d -3, 28, 49, 70, and 91 and immediately stored at -80°C. Before analysis, ruminal and plasma samples from d 28, 49, 70, and 91 were composited. An in-depth, untargeted metabolome profile of the composite rumen and plasma samples and the d -3 samples was developed by using a chemical isotope labeling/liquid chromatography-mass spectrometry (LC-MS)-based technique. Differentially abundant metabolites (taking into account fold change [FC] values and false discovery rates [FDR]) were identified with a volcano plot. In the rumen, compared with the CON diet, supplemental PRO-A increased (FC ≥1.2; FDR ≤0.05) the relative concentrations of 9 metabolites, including 2-hydroxy-2,4-pentadienoic acid, glutaric acid, quinolinic acid, and shikimic acid, and PRO-B increased relative concentrations of 16 metabolites, including 2-hydroxy-2,4-pentadienoic acid, glutaric acid, 16-hydroxypalmitic acid, and 2 propionate precursors (succinic and methylsuccinic acids). Relative to PRO-A, supplemental PRO-B increased (FC ≥1.2; FDR ≤0.05) relative rumen concentrations of 3 metabolites, 16-hydroxypalmitic acid, indole-3-carboxylic acid, and 5-aminopentanoic acid, but reduced relative rumen concentrations of 13 metabolites, including carnitine, threonic acid, and shikimic acid. Compared with the CON diet, relative concentrations of 13 plasma metabolites, including myxochelin A and glyceraldehyde, were increased (FC ≥1.2; FDR ≤0.05) by PRO-A supplementation, whereas those of 9 plasma metabolites, including 4-(2-aminophenyl)-2,4-dioxobutanoic acid, N-acetylornithine, and S-norlaudanosolin, were reduced (FC ≤0.83; FDR ≤0.05). Supplemental PRO-B increased (FC ≥1.2; FDR ≤0.05) relative concentrations of 9 plasma metabolites, including trans-o-hydroxybenzylidenepyruvic acid and 3-methylsalicylaldehyde, and reduced relative concentrations of 4 plasma metabolites, including β-ethynylserine and kynurenine. Pathway analysis of the differentially abundant metabolites in both rumen and plasma revealed that these metabolites are involved in AA and fatty acid metabolism and have antimicrobial and immune-stimulating properties. The results of this study demonstrated that dietary supplementation with either PRO-A or PRO-B altered the plasma and ruminal metabolome. Notably, ruminal and plasma metabolites involved in the metabolism of AA and fatty acids and those with immunomodulatory properties were altered by either or both of the 2 microbial additives.
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Affiliation(s)
- A O Oyebade
- Department of Animal Sciences, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611
| | - G A Taiwo
- Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV 26506
| | - Modoluwamu Idowu
- Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV 26506
| | - T Sidney
- Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV 26506
| | - O Queiroz
- Chr. Hansen A/S, Animal Health and Nutrition, DK-2970 Hørsholm, Denmark
| | - A T Adesogan
- Department of Animal Sciences, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611
| | - D Vyas
- Department of Animal Sciences, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611
| | - I M Ogunade
- Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV 26506.
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Luo W, van Beek TA, Chen B, Zuilhof H, Salentijn GI. Bifunctional Ti 4+-modified paper for selective extraction or removal of phospholipids and paper spray mass spectrometry for bioanalysis in urine and plasma. Anal Chim Acta 2023; 1278:341673. [PMID: 37709425 DOI: 10.1016/j.aca.2023.341673] [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: 06/06/2023] [Revised: 07/28/2023] [Accepted: 07/29/2023] [Indexed: 09/16/2023]
Abstract
BACKGROUND Phospholipids (PLs) are major constituents of cell membranes, play important roles in cell proliferation and death, as well as in signal transduction, and therefore are relevant biomarkers for different pathologies. On the other hand, when the analysis of small compounds, such as therapeutics in blood is desired, then phospholipids are part of the matrix and cause serious interference during analysis. Currently, both the analysis and removal of PLs from biological samples are limited by extensive sample preparation and instrumental separation. RESULTS A fast and simple quantitative Ti4+-modified paper spray tandem mass spectrometric (TiPS-MS/MS) method was established in urine, where the enrichment of phospholipids was achieved, as well as reduction of matrix effects (primarily caused by high salt content) that ultimately led to improved sensitivity and selectivity. The method could achieve a physiologically relevant limit of detection (0.01-0.03 μg mL-1). Also, the usefulness of the Ti4+-modified paper was investigated in the opposite mode, namely for the selective removal of phospholipids from matrices such as plasma. Clonidine is used as model compound, as the detection of this compound is known to suffer from ion suppression by phospholipids. Compared with blank paper spray tandem mass spectrometry, the limit of detection could be improved from 0.3 μg mL-1 to 0.03 μg mL-1 by employing a Ti4+-modified paper on top of the spray tip to capture phospholipids from the sample. SIGNIFICANCE AND NOVELTY A novel Ti4+-modified paper was developed to allow for rapid solid-phase extraction of phospholipids from urine or selective removal from plasma, followed by direct paper spray mass spectrometric detection as a fast and convenient sample preparation and analysis combination. The paper properties are based on the Ti4+ metal ion, which can selectively bind phosphate-containing compounds under acidic conditions, and its applicability was demonstrated in relevant biological matrices.
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Affiliation(s)
- Wei Luo
- Key Laboratory of Phytochemical R&D of Hunan Province and Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, 410081, China; Laboratory of Organic Chemistry, Wageningen University, 6708, WE Wageningen, the Netherlands
| | - Teris A van Beek
- Laboratory of Organic Chemistry, Wageningen University, 6708, WE Wageningen, the Netherlands
| | - Bo Chen
- Key Laboratory of Phytochemical R&D of Hunan Province and Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, 410081, China.
| | - Han Zuilhof
- Key Laboratory of Phytochemical R&D of Hunan Province and Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research of Ministry of Education, Hunan Normal University, Changsha, 410081, China; Laboratory of Organic Chemistry, Wageningen University, 6708, WE Wageningen, the Netherlands.
| | - Gert Ij Salentijn
- Laboratory of Organic Chemistry, Wageningen University, 6708, WE Wageningen, the Netherlands; Wageningen Food Safety Research (WFSR), Wageningen University & Research, 6700, AE Wageningen, the Netherlands.
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Baldan-Martin M, Chaparro M, Gisbert JP. Systematic Review: Urine Biomarker Discovery for Inflammatory Bowel Disease Diagnosis. Int J Mol Sci 2023; 24:10159. [PMID: 37373307 DOI: 10.3390/ijms241210159] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/12/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic, heterogeneous, and inflammatory conditions mainly affecting the gastrointestinal tract. Currently, endoscopy is the gold standard test for assessing mucosal activity and healing in clinical practice; however, it is a costly, time-consuming, invasive, and uncomfortable procedure for the patients. Therefore, there is an urgent need for sensitive, specific, fast and non-invasive biomarkers for the diagnosis of IBD in medical research. Urine is an excellent biofluid for discovering biomarkers because it is non-invasive to sample. In this review, we aimed to summarize proteomics and metabolomics studies performed in both animal models of IBD and humans that identify urinary biomarkers for IBD diagnosis. Future large-scale multi-omics studies should be conducted in collaboration with clinicians, researchers, and industry to make progress toward the development of sensitive and specific diagnostic biomarkers, thereby making personalized medicine possible.
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Affiliation(s)
- Montse Baldan-Martin
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - María Chaparro
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
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9
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Luo Y, Wu J, Liu Y, Shen Y, Zhu F, Wu J, Hu Y. Metabolomics Study of Shaoyao Plants Decoction on the Proximal and Distal Colon in Mice with Dextran Sulfate Sodium-Induced Colitis by UPLC-Q-TOF-MS. Drug Des Devel Ther 2022; 16:4343-4364. [PMID: 36583115 PMCID: PMC9792814 DOI: 10.2147/dddt.s384607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 12/09/2022] [Indexed: 12/24/2022] Open
Abstract
Purpose Shaoyao decoction (SYD) is a traditional Chinese medicine used to treat ulcerative colitis (UC). The exact mechanism of action of SYD in UC treatment is still unclear. Here, we examined the therapeutic effects of SYD in mice with dextran sulfate sodium (DSS)-induced colitis and explored the underlying mechanism. Methods The experimental group was divided into normal control, UC, and SYD treatment groups. The UC model of C57BL/6 mice was induced using 3% (w/v) DSS for 7 days. SYD was orally administered for 7 days. The proximal and distal colonic metabolic profiles were detected using quadrupole-time-of-flight mass spectrometry-based untargeted metabolomics. Results SYD significantly increased weight, reduced disease activity index scores, and ameliorated colon length shortening and pathological damage in mice. In the distal colon, SYD increased the abundance of phosphatidic acid and lysophosphatidylethanolamine and decreased the abundance of lactosylceramide, erythrodiol 3-palmitate, and lysophosphatidylcholine. In the proximal colon, SYD increased the abundance of palmitic acid, cyclonormammein, monoacylglyceride, 13S-hydroxyoctadecadienoic acid, and ceanothine C and decreased the abundance of tetracosahexaenoic acid, phosphatidylserine, and diglyceride. Conclusion Our findings revealed that SYD could alleviate UC by regulating metabolic dysfunction, which provides a reference for further studies on SYD.
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Affiliation(s)
- Yiting Luo
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China
| | - Jin Wu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China
| | - Yingchao Liu
- Academic Affairs Office, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China
| | - Yan Shen
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China
| | - Fangyuan Zhu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China
| | - Jiaqian Wu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China
| | - Yuyao Hu
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China,Correspondence: Yuyao Hu, The Second Affiliated Hospital of Zhejiang Chinese Medical University, 318 Chaowang Road, Hangzhou, People’s Republic of China, Email
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10
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Zhang Y, Yue Q, Zhu H, Song J, Li D, Liu W, Jiang S, Jiang N, Qiu C, Ai J, Zhang Y, Zhang W. Serum Metabolic Correlates of the Antibody Response in Subjects Receiving the Inactivated COVID-19 Vaccine. Vaccines (Basel) 2022; 10:1890. [PMID: 36366398 PMCID: PMC9699138 DOI: 10.3390/vaccines10111890] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/04/2022] [Accepted: 11/07/2022] [Indexed: 01/14/2024] Open
Abstract
BACKGROUND Metabolites are involved in biological process that govern the immune response to infection and vaccination. Knowledge of how metabolites interact with the immune system during immunization with the COVID-19 vaccine is limited. Here, we report that the serum metabolites are correlated with the magnitude of the antibody response in recipients receiving the inactivated COVID-19 vaccine, which provides critical information for studying metabolism regarding the human immune response to vaccination. METHODS 106 healthy volunteers without history of SARS-CoV-2 infection or vaccination were prospectively enrolled to receive the primary series of two doses of inactivated whole-virion SARS-CoV-2 vaccine. The serum samples were collected 2-4 weeks after the second dose. The magnitude of the anti-RBD antibody was quantified using surrogate virus neutralization tests. The profile of metabolites in serum was identified using untargeted metabolomics analysis. RESULTS The level of anti-RBD antibody 14-28 days after the second dose was significantly elevated and its interpersonal variability was diverse in a wide range. Thirty-two samples at extremes of the anti-RBD antibody titer were selected to discover the metabolic correlates. Two hundred and fifteen differential metabolites associated with antibody response independent of body mass index were identified. Pregnenolone and sphingolipid metabolism might be involved in the modulation of the human antibody response to the inactivated COVID-19 vaccine. CONCLUSION We discovered key metabolites as well as those with a related functional significance that might modulate the human immune response to vaccination.
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Affiliation(s)
- Yi Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Qiaoyan Yue
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210006, China
| | - Haojing Zhu
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210006, China
| | - Jieyu Song
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Dingding Li
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210006, China
| | - Wen Liu
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210006, China
| | - Shujun Jiang
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210006, China
- Nanjing Research Center for Infectious Diseases of Integrated Traditional Chinese and Western Medicine, Nanjing 210006, China
| | - Ning Jiang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Chao Qiu
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Jingwen Ai
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Yanliang Zhang
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210006, China
- Nanjing Research Center for Infectious Diseases of Integrated Traditional Chinese and Western Medicine, Nanjing 210006, China
| | - Wenhong Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China
- Shanghai Huashen Institute of Microbes and Infections, No. 6 Lane 1220 Huashan Rd., Shanghai 200031, China
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Zhang K, Xu Y, Yang Y, Guo M, Zhang T, Zong B, Huang S, Suo L, Ma B, Wang X, Wu Y, Brugger D, Chen Y. Gut microbiota-derived metabolites contribute negatively to hindgut barrier function development at the early weaning goat model. ANIMAL NUTRITION 2022; 10:111-123. [PMID: 35663372 PMCID: PMC9136126 DOI: 10.1016/j.aninu.2022.04.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 12/27/2021] [Accepted: 04/11/2022] [Indexed: 11/24/2022]
Abstract
Early weaning induces intestinal injury, leading to a series of long-term symptoms such as inflammation, malabsorption and diarrhea. In this study, we hypothesized that microbes and their metabolites modulate the host's inflammatory response to early weaning stress in a goat model. A total of 18 female Tibetan goat kids (n = 9) were weaned from their mothers at 28 d (D28) and 60 d (D60) postpartum. D60 and D28 groups were fed the same solid diet ad libitum from weaning to 75 d of age. The colonic epithelium was subject to RNA-sequencing, the caecal digesta metabolomics were assessed by liquid chromatography–tandem mass spectrometry (LC-MS/MS), and the caecal microbiota composition was analysed by 16S ribosomal RNA gene sequencing. We found that early weaning substantially increased the colonic pro-apoptotic gene expression of B-cell lymphoma associated X (Bax), caspase-9, and caspase-3, and decreased the expression of zonula occludens-1 (ZO-1) and claudin-1 (P < 0.01). In addition, a significant Bacteroides acidifaciens enrichment was observed in the hindgut of early-weaned goats (P < 0.01), which negatively correlated with lysophosphatidylcholine products. Similarly, the chemokine signaling, IL-17 signaling, and peroxisome proliferators-activated receptor (PPAR) signaling pathways were upregulated in the colonic mucosa of the early-weaned goats. By applying caecal microbiota transplantation from goats to defaunated C57/6J mice, we confirmed that caecal microbiota of D28 goat kids increased the relative abundance of B. acidifaciens and significantly up-regulated the genes of Bax, G protein–coupled receptor (GPR) 109A, GPR 43, fatty acid binding protein 6, nuclear receptor subfamily 1 group H member 3, angiotensin converting enzyme 2, and IL-6 expression (P < 0.05), and decreased ZO-1, and claudin-1 protein expression in the mice jejunum and colon (P < 0.001). These results proposed that the hindgut microbiota and metabolites mediate the barrier function weakening during early weaning, and the relative abundance of B. acidifaciens was negatively correlated with the hindgut barrier gene expression. This study demonstrates how weaning stress can affect key host–microbe interaction regulators in the hindgut, in a lysophosphatidylcholine dependent and independent manner. Furthermore, based on our mice data, these results are transferable to other mammal species.
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12
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Biomarkers of Metabolomics in Inflammatory Bowel Disease and Damp-Heat Syndrome: A Preliminary Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3319646. [PMID: 35815273 PMCID: PMC9270137 DOI: 10.1155/2022/3319646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 05/04/2022] [Accepted: 06/02/2022] [Indexed: 11/17/2022]
Abstract
Aims This study aims to investigate the potential biomarkers of inflammatory bowel disease (IBD) and IBD with damp-heat syndrome (IBD-DH) by metabolomics. Methods Plasma and urine samples were collected from 15 healthy controls and 30 IBD patients, including 15 IBD-DH and 15 IBD with spleen deficiency syndrome (IBD-SD), which was coded as SF8G and SF70 according to the International Classification of Diseases Eleventh Revision (ICD-11) issued by World Health Organization. Pseudotargeted metabolomics method was used based on ultra-high-performance liquid chromatography-high-resolution mass spectrometry and triple-quadrupole mass spectrometry. Results Under the condition of false discovery rate (FDR) < 0.05, variable importance projection (VIP) > 1.0, and fold change (FC) > 1.5 or < 2/3, we found 57 plasma differential metabolites and 20 urinary differential metabolites in IBD. Then, with area under the curve (AUC) ≥ 0.85 and FC ≥ 2 or ≤ 0.3, 11 potential biomarkers were identified, such as acylcarnitine (ACar 20:4, ACar 18:1, and ACar 20:3), 3-indoleacetic acid, hippuric acid, and dehydroepiandrosterone sulfate, which is related to intestinal microbiota and immune response. However, less obvious differences were observed in IBD-DH when compared with IBD-SD. Under the condition of FDR < 0.2, VIP >1.0, and FC > 1.5 or < 2/3, we identified 16 plasma differential metabolites. In urine samples, IBD-DH and IBD-SD had the same metabolite pattern. With AUC ≥ 0.80, 7 differential plasma metabolites, mainly glycerophospholipids, were identified in IBD-DH. Kyoto Encyclopedia of Genes and Genomes analysis indicated that metabolic pathways, such as citrate cycle and amino acids metabolism, were mainly responsible for the distinction between IBD and healthy controls, whereas glycerophospholipid metabolism perturbation was not only a manifestation of IBD but also an important pathway to distinguish two subtypes defined by traditional medicine, IBD-DH and IBD-SD. Conclusion In this study, we found that several metabolites of aromatic acids and lipid derivatives could act as potential biomarkers to discriminate IBD from healthy controls. Glycerophospholipids metabolites might be used to differentiate IBD-DH from IBD-SD.
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13
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Lizhong Decoction () Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling. Chin J Integr Med 2021; 28:1015-1022. [PMID: 34586559 DOI: 10.1007/s11655-021-3299-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/04/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To elucidate the mechanism of Lizhong Decoction (LZD, ) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.
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14
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Geng R, Liu H, Tan K, Wang Z, Wang W. RNase1 can modulate gut microbiota and metabolome after Aeromonas hydrophila infection in blunt snout bream. Environ Microbiol 2021; 23:5258-5272. [PMID: 33973327 DOI: 10.1111/1462-2920.15564] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 04/18/2021] [Accepted: 05/05/2021] [Indexed: 12/13/2022]
Abstract
Pancreatic ribonuclease (RNase1) of Megalobrama amblycephala exhibits both antimicrobial and digestive activity. The gut microbiome improve the digestion and metabolic capacity and enhance the functioning of the immune system of the host against pathogenic bacteria. In this study, we aimed to assess the protective effect of RNase1 on Aeromonas hydrophila-induced inflammation and intestinal microbial metabolism. Megalobrama amblycephala were randomly divided into three groups: control (injected PBS), infection (A. hydrophila-injected), and treatment group (RNase1 pretreatment 24 h before the A. hydrophila injection). The morphological symptoms were significantly alleviated by RNase1. RNase1 reshaped the perturbed gut microbiota by upregulating Proteobacteria and Vibrio richness and downregulating Firmicutes, Chlamydiae, Bacillus, and Gemmobacter richness. The lysophosphatidylcholine, (±) 17 HETE, D- (+) -cellobiose, and PC (20:5) in the treatment group were restored by RNase 1 protein treatment to the level of the control group. In the treatment group, phospholipid metabolism, fatty acid metabolism, glucose metabolism and lipid metabolism were different from the control and infection groups. The proinflammatory factors concentration in intestinal samples significantly increased after A. hydrophila infection. Our results revealed that RNase1 plays an important role in resistance to pathogen invasion, reducing inflammation, and improving intestinal function, thus inhibiting the occurrence of disease.
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Affiliation(s)
- Ruijing Geng
- College of Fisheries, Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, China
| | - Han Liu
- College of Fisheries, Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, China.,Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education/Engineering Technology Research Center for Fish Breeding and Culture in Hubei Province, Wuhan, 430070, China
| | - Kianann Tan
- College of Fisheries, Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, China
| | - Zhiqiang Wang
- College of Fisheries, Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, China
| | - Weimin Wang
- College of Fisheries, Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, China
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15
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Li X, Nakayama K, Goto T, Akamatsu S, Kobayashi T, Shimizu K, Ogawa O, Inoue T. A narrative review of urinary phospholipids: from biochemical aspect towards clinical application. Transl Androl Urol 2021; 10:1829-1849. [PMID: 33968673 PMCID: PMC8100843 DOI: 10.21037/tau-20-1263] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
As a newly emerged discipline, lipidomic studies have focused on the comprehensive characterization and quantification of lipids in a given biological system, which has remarkably advanced in recent years owing to the rapid development of analytical techniques, especially mass spectrometry. Among diverse lipid classes, phospholipids, which have fundamental roles in the formation of cellular membranes, signaling processes, and bioenergetics have gained momentum in several fields of research. The altered composition, concentration, spatial distribution, and metabolism of phospholipids in cells, tissues, and body fluids have been elucidated in various human diseases such as cancer, inflammation, as well as cardiovascular and metabolic disorders. Among the different kinds of phospholipid sources in the human body, urine has not been extensively investigated in recent years owing to the extremely low concentrations of phospholipids and high levels of salts and other contaminants, which can interfere with precise detection. However, with profound advances and rapid expansion in analytical methods, urinary phospholipids have attracted increasing attention in current biomedical research as urine is an easily available source for the discovery of noninvasive biomarkers. In this review, we provide an overview of urinary phospholipids, including their biochemical aspects and clinical applications, aimed at promoting this field of research.
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Affiliation(s)
- Xin Li
- Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kenji Nakayama
- Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takayuki Goto
- Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shusuke Akamatsu
- Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takashi Kobayashi
- Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koji Shimizu
- Clinical Research Center for Medical Equipment Development, Kyoto University Hospital, Kyoto, Japan
| | - Osamu Ogawa
- Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takahiro Inoue
- Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Japan
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16
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Zhai L, Huang T, Xiao HT, Wu PG, Lin CY, Ning ZW, Zhao L, Kwan HYA, Hu XJ, Wong HLX, Li XQ, Bian ZX. Berberine Suppresses Colonic Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis Through Inhibition of Cytosolic Phospholipase A2 Activity. Front Pharmacol 2021; 11:576496. [PMID: 33658925 PMCID: PMC7919193 DOI: 10.3389/fphar.2020.576496] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 10/08/2020] [Indexed: 12/16/2022] Open
Abstract
Ulcerative colitis (UC) causes chronic inflammation and damage to the colonic mucosal layer. Recent studies have reported significant changes in phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in UC patients and oral administration of PC has considerable therapeutic effects against UC, suggesting the metabolism of phosphatidylcholine may be involved in the UC development. Our previous work has demonstrated that berberine effectively suppresses inflammation and protects colonic mucosa injury in DSS-induced colitic mice. However, whether the therapeutic effects of berberine are attributed to its action on the PC metabolism remains unknown. In the present study, we have shown that berberine significantly reduces the lysophosphatidylcholine (LPC) levels in the sera of DSS-induced experimental colitis mice and LPS-stimulated macrophage RAW 264.7 cells. The cytosolic phospholipase A2a (PLA2G4A), an enzyme for hydrolyzing PC to LPC, was found to be up-regulated in the colon tissue of experimental colitis mice and inflamed macrophage RAW 264.7 cells. We then demonstrated berberine inhibits the phosphorylation of cytosolic phospholipase A2a (PLA2G4A) in the colon tissue of experimental colitis mice and inflamed macrophage RAW 264.7 cells. Subsequently, we revealed berberine suppressed the expression of pro-inflammatory factors including TNF-alpha and IL-6 through regulating PLA2G4A dysfunction in macrophage RAW 264.7 cells. Mechanistically, we found that berberine directly binds to PLA2G4A and inhibits MAPK/JNK signaling pathway to inhibit PLA2G4A activity in inflammatory status. Therefore, we concluded that berberine inhibits colonic PLA2G4A activity to ameliorate colonic inflammation in experimental colitic mice, suggesting modulation of the PC metabolism via PLA2G4A might be beneficial for establishing new therapies strategy for UC.
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Affiliation(s)
- Lixiang Zhai
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong
| | - Tao Huang
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong
| | - Hai-Tao Xiao
- School of Pharmacy, Health Science Center, Shenzhen University, Shenzhen, China
| | - Pei-Gen Wu
- School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China
| | - Cheng-Yuan Lin
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong
| | - Zi-Wan Ning
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong
| | - Ling Zhao
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong
| | - Hiu Yee Anna Kwan
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong
| | - Xian-Jing Hu
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong
| | | | - Xian-Qian Li
- School of Pharmacy, Health Science Center, Shenzhen University, Shenzhen, China
| | - Zhao-Xiang Bian
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong.,Shenzhen Research Institute and Continuing Education, Hong Kong Baptist University, Shenzhen, China
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17
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Liu K, Jia B, Zhou L, Xing L, Wu L, Li Y, Lu J, Zhang L, Guan S. Ultraperformance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry-Based Metabolomics and Lipidomics Identify Biomarkers for Efficacy Evaluation of Mesalazine in a Dextran Sulfate Sodium-Induced Ulcerative Colitis Mouse Model. J Proteome Res 2020; 20:1371-1381. [PMID: 33356298 DOI: 10.1021/acs.jproteome.0c00757] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This study aims to identify biomarkers for evaluating the therapeutic efficacy of mesalazine on ulcerative colitis by metabolomics and lipidomics. A dextran sulfate sodium-induced mouse model was used. The disease status was assessed by a disease activity index, the TNF-α level of colon was measured by an enzyme-linked immunosorbent assay, and the pathological changes of colon tissue was examined by hematoxylin-eosin staining. Serum metabolomics and lipidomics analysis based on ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were applied to decipher the metabolic profile changes. Multivariate analysis was applied to differentiate the metabolites of controls, models, and mesalazine-treated mice. By the receiver operating characteristic (ROC) analysis, 40 differential metabolites with an area under curve (AUC) >0.80 were screened out between control and model groups. Among them, four potential biomarkers (palmitoyl glucuronide, isobutyrylglycine, PC (20:3 (5Z, 8Z, 11Z)/15:0) and L-arginine) had a signficantly reversed level of peak areas in the mesalazine group, and three of them were closely correlated with mesalazine efficacy by linear regression analysis. Furthermore, metabolic pathway analysis revealed several dysregulated pathways in colitis mice, including glycerophospholipid metabolism, pyrimidine metabolism, linoleic acid metabolism, arginine biosynthesis, etc. This study indicates that serum metabolomics is a useful approach that can noninvasively evaluate the therapeutic effect and provide unique insights into the underlying mechanism of mesalazine.
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Affiliation(s)
- Kun Liu
- MOE Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P.R. China
| | - Bingjie Jia
- MOE Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P.R. China
| | - Liping Zhou
- Evaluation and Monitoring Center of Occupational Health, Guangzhou Twelfth People's Hospital, Guangzhou 510620, P.R. China
| | - Lei Xing
- MOE Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P.R. China
| | - Lvying Wu
- MOE Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P.R. China
| | - Yuanyuan Li
- MOE Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P.R. China
| | - Jungang Lu
- Agilent Technologies (China) Co., Ltd., Guangzhou 510613, P.R. China
| | - Lei Zhang
- MOE Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P.R. China
| | - Su Guan
- MOE Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P.R. China
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18
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Wei L, Zeng B, Zhang S, Li F, Kong F, Ran H, Wei HJ, Zhao J, Li M, Li Y. Inbreeding Alters the Gut Microbiota of the Banna Minipig. Animals (Basel) 2020; 10:ani10112125. [PMID: 33207622 PMCID: PMC7697339 DOI: 10.3390/ani10112125] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/08/2020] [Accepted: 11/11/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary The mammalian gut microbiota is an indispensable part of host health. The gut microbiota plays a crucial role in nutrient digestibility, preventing colonization of pathogens and maintaining the host immune system. Host genetics has been conclusively shown to closely related to gut microbiota. Inbreeding can cause a decrease of the host’s genetic diversity, however, remarkably little is understood about the gut microbiota of pigs during inbreeding. The Banna minipig inbred is the world’s first successful large mammalian experimental animal inbred line since 1980 from full and half-siblings of the Diannan small-ear pig. Now, Banna minipig inbred has been inbred for over 37 generations, and the inbreeding coefficient is more than 99%. This study is the first to characterize and compare the composition and function of gut microbiota between the Diannan small-ear pig and Banna minipig inbred, aiming to better understand the influence of inbreeding on the gut microbiota. Abstract The gut microbiota coevolve with the host and can be stably transmitted to the offspring. Host genetics plays a crucial role in the composition and abundance of gut microbiota. Inbreeding can cause a decrease of the host’s genetic diversity and the heterozygosity. In this study, we used 16S rRNA gene sequencing to compare the differences of gut microbiota between the Diannan small-ear pig and Banna minipig inbred, aiming to understand the impact of inbreeding on the gut microbiota. Three dominant bacteria (Stenotrophlomonas, Streptococcus, and Lactobacillus) were steadily enriched in both the Diannan small-ear pig and Banna minipig inbred. After inbreeding, the gut microbiota alpha diversity and some potential probiotics (Bifidobacterium, Tricibacter, Ruminocaccae, Christensenellaceae, etc.) were significantly decreased, while the pathogenic Klebsiella bacteria was significantly increased. In addition, the predicted metagenomic analysis (PICRUSt2) indicated that several amino acid metabolisms (‘‘Valine, leucine, and isoleucine metabolism’’, ‘‘Phenylalanine, tyrosine, and tryptophan biosynthesis’’, ‘‘Histidine metabolism’’) were also markedly decreased after the inbreeding. Altogether our data reveal that host inbreeding altered the composition and the predicted function of the gut microbiome, which provides some data for the gut microbiota during inbreeding.
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Affiliation(s)
- Limin Wei
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (L.W.); (B.Z.); (S.Z.); (F.L.); (H.R.)
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, School of Life Science and Engineering, Foshan University, Foshan 528231, China
| | - Bo Zeng
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (L.W.); (B.Z.); (S.Z.); (F.L.); (H.R.)
| | - Siyuan Zhang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (L.W.); (B.Z.); (S.Z.); (F.L.); (H.R.)
| | - Feng Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (L.W.); (B.Z.); (S.Z.); (F.L.); (H.R.)
| | - Fanli Kong
- College of Life Science, Sichuan Agricultural University, Ya’an 625014, China;
| | - Haixia Ran
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (L.W.); (B.Z.); (S.Z.); (F.L.); (H.R.)
| | - Hong-Jiang Wei
- Key Laboratory of Animal Gene Editing and Animal Cloning in Yunnan Province, Yunnan Agricultural University, Kunming 650201, China;
| | - Jiangchao Zhao
- Department of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR 72701, USA;
| | - Mingzhou Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (L.W.); (B.Z.); (S.Z.); (F.L.); (H.R.)
- Correspondence: (M.L.); (Y.L.)
| | - Ying Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; (L.W.); (B.Z.); (S.Z.); (F.L.); (H.R.)
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, School of Life Science and Engineering, Foshan University, Foshan 528231, China
- Correspondence: (M.L.); (Y.L.)
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Liu R, Qiao S, Shen W, Liu Y, Lu Y, Liangyu H, Guo Z, Gong J, Shui G, Li Y, Zhu W. Disturbance of Fatty Acid Desaturation Mediated by FADS2 in Mesenteric Adipocytes Contributes to Chronic Inflammation of Crohn's Disease. J Crohns Colitis 2020; 14:1581-1599. [PMID: 32365195 DOI: 10.1093/ecco-jcc/jjaa086] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS The aim of this study was to investigate the metabolic profile of mesenteric adipocytes and the correlations between key metabolic changes and local inflammation in the context of Crohn's disease [CD]. METHODS Metabolic dysfunction was shown to be regulated by fatty acid desaturase-2 [FADS2], through metabolomics and functional analyses of mesenteric adipose tissue biopsies and primary mesenteric adipocytes isolated from surgical specimens collected from CD patients and control subjects. FADS2 was overexpressed in vitro and in vivo using a lentiviral vector and an adeno-associated virus [AAV], respectively. The interaction between mesenteric adipocytes and inflammation responses was evaluated by establishing a cell coculture system and a FADS2-AAV treated animal model; 3T3-L1 cells were used to elucidate the mechanism underlying FADS2 deregulation. RESULTS We observed significant changes in the levels of metabolites involved in the multi-step synthesis of long-chain polyunsaturated fatty acids [PUFAs]. Gas chromatography analysis revealed impaired desaturation fluxes towards the n-6 and n-3 pathways, which are associated with reduced FADS2 activity in human mesentery tissue. Decreased FADS2 expression at both mRNA and protein levels was confirmed in surgical specimens. The restoration of FADS2 expression, which allows for the endogenous conversion of n-3 fatty acids into proresolving lipid mediators, resulted in a significant reduction in pro-inflammatory macrophage infiltration and attenuated expression of inflammatory cytokines or adipokines. CONCLUSIONS These findings indicate that impaired fatty acid desaturation and lipid mediator imbalance within mesenteric adipose tissue contributes to chronic inflammation in CD. The therapeutic role of FADS2 may lead to improved CD treatment.
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Affiliation(s)
- Ruiqing Liu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.,Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shuaihua Qiao
- Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Weisong Shen
- Department of Gastroenterological Surgery, Peking University People's Hospital, Peking, China
| | - Yue Liu
- State Key Laboratory of Pharmaceutical Biotechnology and Nanjing Drum Tower Hospital, Model Animal Research Center, Nanjing University, Nanjing, China
| | - Yun Lu
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Huang Liangyu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Zhen Guo
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jianfeng Gong
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Guanghou Shui
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, University of Chinese Academy of Sciences, Beijing, China
| | - Yi Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Weiming Zhu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
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Tang Q, Cang S, Jiao J, Rong W, Xu H, Bi K, Li Q, Liu R. Integrated study of metabolomics and gut metabolic activity from ulcerative colitis to colorectal cancer: The combined action of disordered gut microbiota and linoleic acid metabolic pathway might fuel cancer. J Chromatogr A 2020; 1629:461503. [PMID: 32858455 DOI: 10.1016/j.chroma.2020.461503] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 08/14/2020] [Accepted: 08/19/2020] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is one of the most serious complications of ulcerative colitis (UC). Altered gut microbiota is implicated in the development of CRC and metabolic perturbations are often associated with changes in the gut microbiome composition. Given the links between gut microbiome and the metabolic profiles in the body, an approach involving ultra-high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) metabolomics and 16S rDNA sequencing technology was applied to trace the development UC into CRC in rats. The study identified 11 differential metabolites related to both UC and CRC, which mainly referred to the linoleic acid metabolism. Among these, linoleic acid and 12‑hydroxy‑8,10-octadecadienoic acid could serve as key biomarkers for the development of UC into CRC. Besides, a significant change was observed in the microflora structure during the development from UC to CRC; this mainly involved a gradual increase in Escherichia-Shigella and a gradual decrease in Lactobacillus. In addition, Pearson's correlation analysis revealed strong correlations between intestinal microflora-related metabolites and specific intestinal microflora, which indicated both of them can promote the transition of UC to CRC. The results of the present study provided positive support for the involvement of intestinal microflora and host metabolism in the pathophysiological mechanism that is responsible for the development of UC into CRC. This information can help understand the risk for CRC that accompanies a diagnosis of UC and also provide different means of targeting these differential metabolites and intestinal microbiota to avoid UC-induced CRC.
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Affiliation(s)
- Qi Tang
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
| | - Song Cang
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
| | - Jiao Jiao
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
| | - Weiwei Rong
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
| | - Huarong Xu
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
| | - Kaishun Bi
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
| | - Qing Li
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
| | - Ran Liu
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
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Translational Potential of Metabolomics on Animal Models of Inflammatory Bowel Disease-A Systematic Critical Review. Int J Mol Sci 2020; 21:ijms21113856. [PMID: 32485793 PMCID: PMC7312423 DOI: 10.3390/ijms21113856] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 05/24/2020] [Accepted: 05/26/2020] [Indexed: 12/16/2022] Open
Abstract
In the development of inflammatory bowel disease (IBD), the gut microbiota has been established as a key factor. Recently, metabolomics has become important for understanding the functional relevance of gut microbial changes in disease. Animal models for IBD enable the study of factors involved in disease development. However, results from animal studies may not represent the human situation. The aim of this study was to investigate whether results from metabolomics studies on animal models for IBD were similar to those from studies on IBD patients. Medline and Embase were searched for relevant studies up to May 2017. The Covidence systematic review software was used for study screening, and quality assessment was conducted for all included studies. Data showed a convergence of ~17% for metabolites differentiated between IBD and controls in human and animal studies with amino acids being the most differentiated metabolite subclass. The acute dextran sodium sulfate model appeared as a good model for analysis of systemic metabolites in IBD, but analytical platform, age, and biological sample type did not show clear correlations with any significant metabolites. In conclusion, this systematic review highlights the variation in metabolomics results, and emphasizes the importance of expanding the applied detection methods to ensure greater coverage and convergence between the various different patient phenotypes and animal models of inflammatory bowel disease.
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22
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Probiotic treatment induced change of inflammation related metabolites in IBS-D patients/double-blind, randomized, placebo-controlled trial. Food Sci Biotechnol 2019; 29:837-844. [PMID: 32523793 DOI: 10.1007/s10068-019-00717-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 11/11/2019] [Accepted: 11/12/2019] [Indexed: 02/07/2023] Open
Abstract
There have been many studies suggesting that probiotics are effective in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). However, its mechanism of action as well as prediction of response is still to be elucidated. In the present study, to find out metabolomic characteristics of probiotic effect in IBS-D, we compared IBS symptom changes and metabolomic characteristics in the subjects' urine samples between multi-strain probiotics (one strain of Lactobacillus sp. and four strains of Bifidobacterium sp.) group (n = 32) and placebo group (n = 31). After 8 weeks' administration (3 times/day), dissatisfaction in bowel habits and stool frequencies were significantly improved. Also, probiotics group had significantly changed seven metabolites including palmitic acid methyl ester (PAME) and 4,6-dihydroxyquinoline, 4-(2-aminophenyl)-2,4-dioxobutanoic acid (DOBA). According to IBS-SSS and IBS-QoL questionnaires, IBS-SSS responders showed higher PAME levels and IBS-QoL responders showed lower DOBA levels. This suggests potential role of these metabolites as a biomarker to predict probiotics effect in IBS-D patients.
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23
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Guan S, Jia B, Chao K, Zhu X, Tang J, Li M, Wu L, Xing L, Liu K, Zhang L, Wang X, Gao X, Huang M. UPLC–QTOF-MS-Based Plasma Lipidomic Profiling Reveals Biomarkers for Inflammatory Bowel Disease Diagnosis. J Proteome Res 2019; 19:600-609. [PMID: 31821004 DOI: 10.1021/acs.jproteome.9b00440] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Su Guan
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P. R. China
| | - Bingjie Jia
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P. R. China
| | - Kang Chao
- Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P. R. China
| | - Xia Zhu
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
| | - Jian Tang
- Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P. R. China
| | - Miao Li
- Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P. R. China
| | - Lvying Wu
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P. R. China
| | - Lei Xing
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P. R. China
| | - Kun Liu
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P. R. China
| | - Lei Zhang
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P. R. China
| | - Xueding Wang
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
| | - Xiang Gao
- Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, P. R. China
| | - Min Huang
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China
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24
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Oza M, Becker W, Gummadidala PM, Dias T, Omebeyinje MH, Chen L, Mitra C, Jesmin R, Chakraborty P, Sajish M, Hofseth LJ, Banerjee K, Wang Q, Moeller PDR, Nagarkatti M, Nagarkatti P, Chanda A. Acute and short-term administrations of delta-9-tetrahydrocannabinol modulate major gut metabolomic regulatory pathways in C57BL/6 mice. Sci Rep 2019; 9:10520. [PMID: 31324830 PMCID: PMC6642200 DOI: 10.1038/s41598-019-46478-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Accepted: 06/19/2019] [Indexed: 01/07/2023] Open
Abstract
Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound in Cannabis, which is studied extensively for its medicinal value. A central gap in the science is the underlying mechanisms surrounding THC's therapeutic effects and the role of gut metabolite profiles. Using a mass-spectrometry based metabolomics, we show here that intraperitoneal injection of THC in C57BL/6 mice modulates metabolic profiles that have previously been identified as integral to health. Specifically, we investigated the effects of acute (single THC injection denoted here as '1X') and short -term (five THC injections on alternate days denoted as '5X') THC administration on fecal and intestinal tissue metabolite profiles. Results are consistent with the hypothesis that THC administration alters host metabolism by targeting two prominent lipid metabolism pathways: glycerophospholipid metabolism and fatty acid biosynthesis.
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Affiliation(s)
- Megha Oza
- Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - William Becker
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA
| | - Phani M Gummadidala
- Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Travis Dias
- Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Mayomi H Omebeyinje
- Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Li Chen
- Creative Proteomics Inc., Shirley, New York, USA
| | - Chandrani Mitra
- Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Rubaiya Jesmin
- Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | | | - Mathew Sajish
- Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA
| | - Lorne J Hofseth
- Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA
| | | | - Qian Wang
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA
| | - Peter D R Moeller
- National Ocean Service, Hollings Marine Laboratory, Charleston, SC, USA
| | - Mitzi Nagarkatti
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA
| | - Prakash Nagarkatti
- Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA
| | - Anindya Chanda
- Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA.
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Zhang Y, Bian X, Yang J, Wu H, Wu JL, Li N. Metabolomics of Clinical Poisoning by Aconitum Alkaloids Using Derivatization LC-MS. Front Pharmacol 2019; 10:275. [PMID: 30967780 PMCID: PMC6439482 DOI: 10.3389/fphar.2019.00275] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 03/04/2019] [Indexed: 12/13/2022] Open
Abstract
The root of Aconitum kusnezoffii (Caowu in Chinese, CW) is not only commonly used as a traditional Chinese medicine (TCM), but also served as a tonic in China. Due to its high toxicity, clinical poisoning cases induced by CW have frequently been reported. However, the mechanism is still unclear. In this study, Aconitum alkaloids and altered endogenous metabolites in CW poisoning patients were investigated to elucidate the possible intoxication mechanism. Eighteen alkaloids, including 6 toxic diester diterpenoid alkaloids (DDAs), were determined from the sera of patients. At the same time, 5-(diisopropylamino)amylamine (DIAAA) derivatization-ultrahigh performance liquid chromatography- quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS) approach was applied in the metabolomics analysis to find much more carboxyl-containing metabolites (CCMs), which are the essential components for life and critical to elucidate the mechanism of toxicity. As a result, 32 altered metabolites after poisoning were identified. Among them, hydroxyeicosatetraenoic acids (HETEs) and some dicarboxylic acids were first found to be related to Aconitum alkaloids toxicity. Finally, biological pathway analysis indicated that the significantly changed metabolites were primarily involved in amino acid metabolism, TCA cycle, fatty acid metabolism, pyruvate metabolism, arachidonic acid metabolism, sphingolipid metabolism and so on. These results can not only provide more information on the mechanism of CW intoxication but also help the clinical diagnosis of CW poisoning.
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Affiliation(s)
- Yida Zhang
- State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macao, China
| | - Xiqing Bian
- State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macao, China
| | - Jing Yang
- Department of Emergency, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Haiying Wu
- Department of Emergency, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jian-Lin Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macao, China
| | - Na Li
- State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macao, China
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Kong M, Liu HH, Wu J, Shen MQ, Wang ZG, Duan SM, Zhang YB, Zhu H, Li SL. Effects of sulfur-fumigation on the pharmacokinetics, metabolites and analgesic activity of Radix Paeoniae Alba. JOURNAL OF ETHNOPHARMACOLOGY 2018; 212:95-105. [PMID: 29080828 DOI: 10.1016/j.jep.2017.10.023] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 09/22/2017] [Accepted: 10/23/2017] [Indexed: 05/28/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Radix Paeoniae Alba (Baishao, BS), one of the most commonly used traditional Chinese medicinal herbs, has many pharmacological effects including analgesic activity. Previous studies found that sulfur-fumigation, a post-harvest handling process developed to prevent mold contamination of medicinal herbs, altered the quality of BS. However, whether sulfur-fumigation affects the pharmacokinetics, safety and efficacy of BS warrants further investigation. AIM OF THE STUDY To evaluate the feasibility of sulfur-fumigation as a post-harvest handling process of BS from the viewpoints of pharmacokinetics, safety and efficacy. MATERIALS AND METHODS The pharmacokinetic behaviors of four active components of BS and one characteristic component of sulfur-fumigated BS (S-BS) were evaluated by high performance liquid chromatography triple quadrupole mass spectrometry (HPLC-TQ-MS/MS). The safety was investigated using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) based metabolomics approach after intragastric (i.g.) administration of non-fumigated BS (N-BS) and S-BS in rats. The analgesic efficacy was compared using hot-plate test in mice, after i.g. administration of N-BS and S-BS, at both high and low dosages. RESULTS Systemic exposures of paeoniflorin and oxypaeoniflorin, two analgesic components of BS, were significantly decreased in the S-BS treated group compared to the N-BS treated group, while paeoniflorin sulfonate, one of the sulfur-containing derivatives of S-BS, was detected in all time-points of S-BS treated group with the area under the plasma concentration-time curve (AUC0-t) and the maximum plasma concentration (Cmax) as high as 7077.06 ± 2232.97ng/mL*h and 1641.42 ± 634.79ng/mL respectively, which indicated that sulfur-fumigation altered the pharmacokinetic behaviors of BS. Besides, paeoniflorin sulfonate and its four metabolites with ambiguous toxicities, as well as one endogenous metabolite p-cresol glucuronide, the biomarker of disordered homeostasis of intestinal bacteria and bile acid, were identified as the characteristic metabolites in S-BS administered rats, suggesting that sulfur-fumigation reduced the safety of BS. Furthermore, the analgesic effects at both low and high dosages were decreased in different extent when compared to N-BS administered groups, indicating that sulfur-fumigation weakened the efficacy of BS. CONCLUSION Sulfur-fumigation altered the pharmacokinetics, as well as reduced the safety and efficacy of BS, suggesting that sulfur-fumigation is not recommended for post-harvest handling of BS.
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Affiliation(s)
- Ming Kong
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China
| | - Huan-Huan Liu
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China
| | - Jie Wu
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, PR China
| | - Ming-Qin Shen
- Department of Pharmacology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China
| | - Zhi-Gang Wang
- Department of Pharmacology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China
| | - Su-Min Duan
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China
| | - Yan-Bo Zhang
- School of Chinese Medicine, The University of Hong Kong, Hong Kong Special Administrative Region
| | - He Zhu
- Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, PR China.
| | - Song-Lin Li
- Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine and Jiangsu Branch of China Academy of Chinese Medical Sciences, Nanjing 210028, PR China.
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Jiang P, Trimigno A, Stanstrup J, Khakimov B, Viereck N, Engelsen SB, Sangild PT, Dragsted LO. Antibiotic Treatment Preventing Necrotising Enterocolitis Alters Urinary and Plasma Metabolomes in Preterm Pigs. J Proteome Res 2017; 16:3547-3557. [PMID: 28871782 DOI: 10.1021/acs.jproteome.7b00263] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Necrotising enterocolitis (NEC) is a serious gut inflammatory condition in premature neonates, onset and development of which depend on the gut microbiome. Attenuation of the gut microbiome by antibiotics can reduce NEC incidence and severity. However, how the antibiotics-suppressed gut microbiome affects the whole-body metabolism in NEC-sensitive premature neonates is unknown. In formula-fed preterm pigs, used as a model for preterm infants, plasma and urinary metabolomes were investigated by LC-MS and 1H NMR, with and without antibiotic treatment immediately after birth. While it reduced the gut microbiome density and NEC lesions as previously reported, the antibiotic treatment employed in the current study affected the abundance of 44 metabolites in different metabolic pathways. In antibiotics-treated pigs, tryptophan metabolism favored the kynurenine pathway, relative to the serotonin pathway, as shown by specific metabolites. Metabolites associated with the gut microbiome, including 3-phenyllactic acid, 4-hydroxyphenylacetic acid, and phenylacetylglycine, all from phenylalanine, and three bile acids showed lower levels in the antibiotics-treated pigs where the gut microbiome was extensively attenuated. Findings in the current study warrant further investigation of metabolic and developmental consequences of antibiotic treatment in preterm neonates.
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Affiliation(s)
| | - Alessia Trimigno
- Department of Agricultural and Food Sciences, University of Bologna , Campus di Scienze degli Alimenti, Cesena, Italy
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Metabolomics highlights pharmacological bioactivity and biochemical mechanism of traditional Chinese medicine. Chem Biol Interact 2017; 273:133-141. [PMID: 28619388 DOI: 10.1016/j.cbi.2017.06.011] [Citation(s) in RCA: 154] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Revised: 05/13/2017] [Accepted: 06/12/2017] [Indexed: 01/08/2023]
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Yu X, Yang G, Jiang H, Lin S, Liu Y, Zhang X, Zeng H, Su Z, Huang S, Shen L, Zhang X. Patchouli oil ameliorates acute colitis: A targeted metabolite analysis of 2,4,6-trinitrobenzenesulfonic acid-induced rats. Exp Ther Med 2017; 14:1184-1192. [PMID: 28810577 DOI: 10.3892/etm.2017.4577] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 10/28/2016] [Indexed: 12/30/2022] Open
Abstract
The incidence of inflammatory bowel disease (IBD), characterized by chronic, relapsing intestinal inflammation, has continually increased in recent years. A previous study by our group identified five potential metabolic markers possibly associated with the pathology of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced IBD in rats. The present study aimed to examine the potential therapeutic effects of the essential oil of Pogostemon cablin (also known as patchouli; PO) on TNBS-induced rats and investigate the concomitant metabolic changes by targeting the previously identified potential markers. Pogostemon cablin is widely used to treat gastrointestinal diseases, including IBD, in China. The results of the present study showed that PO (270 mg/kg, rectal instillation) significantly alleviated colonic damage and reduced disease activity indicators and colonic myeloperoxidase in TNBS-induced rats. In addition, a targeted metabolic profiling study identified that four metabolites were elevated in the urine of the animals in the TNBS group, which were significantly inhibited by treatment with PO: Two tryptophan metabolites [4-(2-aminophenyl)-2,4-dioxobutanoic acid and 4,6-cihydroxyquinoline] and two gut microbial metabolites (phenylacetylglycine and p-cresol glucuronide). Taken together, these findings suggested that PO ameliorated the symptoms of TNBS-induced IBD and reversed the metabolic changes potentially associated with TNBS-induced IBD in rats.
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Affiliation(s)
- Xiuting Yu
- Department of Pharmacy, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Guanghua Yang
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Hua Jiang
- Analysis Center of Shimadzu Enterprise Management (China) Co., Ltd., Guangzhou, Guangdong 510010, P.R. China
| | - Shuhai Lin
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 999077, Hong Kong SAR, P.R. China
| | - Yuhong Liu
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Xie Zhang
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Huifang Zeng
- Department of Pharmacy, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Ziren Su
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Song Huang
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
| | - Linlin Shen
- Analysis Center of Shimadzu Enterprise Management (China) Co., Ltd., Guangzhou, Guangdong 510010, P.R. China
| | - Xiaojun Zhang
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
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Choo JM, Trim PJ, Leong LEX, Abell GCJ, Brune C, Jeffries N, Wesselingh S, Dear TN, Snel MF, Rogers GB. Inbred Mouse Populations Exhibit Intergenerational Changes in Intestinal Microbiota Composition and Function Following Introduction to a Facility. Front Microbiol 2017; 8:608. [PMID: 28443082 PMCID: PMC5387074 DOI: 10.3389/fmicb.2017.00608] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 03/24/2017] [Indexed: 12/31/2022] Open
Abstract
Inbred mice are used to investigate many aspects of human physiology, including susceptibility to disease and response to therapies. Despite increasing evidence that the composition and function of the murine intestinal microbiota can substantially influence a broad range of experimental outcomes, relatively little is known about microbiome dynamics within experimental mouse populations. We investigated changes in the intestinal microbiome between C57BL/6J mice spanning six generations (assessed at generations 1, 2, 3, and 6), following their introduction to a stringently controlled facility. Fecal microbiota composition and function were assessed by 16S rRNA gene amplicon sequencing and liquid chromatography mass spectrometry, respectively. Significant divergence of the intestinal microbiota between founder and second generation mice, as well as continuing inter-generational variance, was observed. Bacterial taxa whose relative abundance changed significantly through time included Akkermansia, Turicibacter, and Bifidobacterium (p < 0.05), all of which are recognized as having the potential to substantially influence host physiology. Shifts in microbiota composition were mirrored by corresponding differences in the fecal metabolome (r = 0.57, p = 0.0001), with notable differences in levels of tryptophan pathway metabolites and amino acids, including glutamine, glutamate and aspartate. We related the magnitude of changes in the intestinal microbiota and metabolome characteristics during acclimation to those observed between populations housed in separate facilities, which differed in regards to husbandry, barrier conditions and dietary intake. The microbiome variance reported here has implications for experimental reproducibility, and as a consequence, experimental design and the interpretation of research outcomes across wide range of contexts.
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Affiliation(s)
- Jocelyn M Choo
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, AdelaideSA, Australia
| | - Paul J Trim
- Lysosomal Diseases Research Unit, Nutrition and Metabolism Theme, South Australia Health and Medical Research Institute, AdelaideSA, Australia
| | - Lex E X Leong
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, AdelaideSA, Australia
| | - Guy C J Abell
- School of Medicine, Flinders University, AdelaideSA, Australia
| | - Carly Brune
- Bioresources facility, South Australia Health and Medical Research Institute, AdelaideSA, Australia
| | - Nicole Jeffries
- Bioresources facility, South Australia Health and Medical Research Institute, AdelaideSA, Australia
| | - Steve Wesselingh
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, AdelaideSA, Australia
| | - T N Dear
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, AdelaideSA, Australia
| | - Marten F Snel
- Lysosomal Diseases Research Unit, Nutrition and Metabolism Theme, South Australia Health and Medical Research Institute, AdelaideSA, Australia
| | - Geraint B Rogers
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, AdelaideSA, Australia.,School of Medicine, Flinders University, AdelaideSA, Australia
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Sarosiek I, Schicho R, Blandon P, Bashashati M. Urinary metabolites as noninvasive biomarkers of gastrointestinal diseases: A clinical review. World J Gastrointest Oncol 2016; 8:459-465. [PMID: 27190585 PMCID: PMC4865713 DOI: 10.4251/wjgo.v8.i5.459] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 01/12/2016] [Accepted: 03/09/2016] [Indexed: 02/05/2023] Open
Abstract
The diagnosis of gastrointestinal (GI) disorders is usually based on invasive techniques such as endoscopy. A key important factor in GI cancer is early diagnosis which warrants development of non- or less-invasive diagnostic techniques. In addition, monitoring and surveillance are other important parts in the management of GI diseases. Metabolomics studies with nuclear magnetic resonance and mass spectrometry can measure the concentration of more than 3000 chemical compounds in the urine providing possible chemical signature in different diseases and during health. In this review, we discuss the urinary metabolomics signature of different GI diseases including GI cancer and elaborate on how these biomarkers could be used for the classification, early diagnosis and the monitoring of the patients. Moreover, we discuss future directions of this still evolving field of research.
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Soubières AA, Poullis A. Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease. World J Gastrointest Pharmacol Ther 2016; 7:41-50. [PMID: 26855811 PMCID: PMC4734953 DOI: 10.4292/wjgpt.v7.i1.41] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 10/06/2015] [Accepted: 11/11/2015] [Indexed: 02/06/2023] Open
Abstract
There is currently no gold standard test for the diagnosis of inflammatory bowel disease (IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis (UC) or Crohn’s disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn’s. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Non-invasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.
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Liu J, Xiao HT, Wang HS, Mu HX, Zhao L, Du J, Yang D, Wang D, Bian ZX, Lin SH. Halofuginone reduces the inflammatory responses of DSS-induced colitis through metabolic reprogramming. MOLECULAR BIOSYSTEMS 2016; 12:2296-2303. [DOI: 10.1039/c6mb00154h] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
Halofuginone inhibits both HIF-1alpha and incomplete FAO to reduce the inflammatory response in DSS-induced colitis.
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Affiliation(s)
- Jing Liu
- School of Pharmaceutical Sciences
- Sun Yat-Sen University
- Guangzhou 510006
- China
- School of Chinese Medicine
| | - Hai-Tao Xiao
- School of Chinese Medicine
- Hong Kong Baptist University
- China
- School of Pharmacy
- Guizhou Medicial University
| | - Hong-Sheng Wang
- School of Pharmaceutical Sciences
- Sun Yat-Sen University
- Guangzhou 510006
- China
| | - Huai-Xue Mu
- School of Chinese Medicine
- Hong Kong Baptist University
- China
| | - Ling Zhao
- School of Chinese Medicine
- Hong Kong Baptist University
- China
| | - Jun Du
- School of Pharmaceutical Sciences
- Sun Yat-Sen University
- Guangzhou 510006
- China
| | - Depo Yang
- School of Pharmaceutical Sciences
- Sun Yat-Sen University
- Guangzhou 510006
- China
| | - Dongmei Wang
- School of Pharmaceutical Sciences
- Sun Yat-Sen University
- Guangzhou 510006
- China
| | | | - Shu-Hai Lin
- School of Chinese Medicine
- Hong Kong Baptist University
- China
- Department of Biochemistry and Molecular Cell Biology
- Shanghai Key Laboratory for Tumor Microenvironment and Inflammation
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Hou W, Zhong D, Zhang P, Li Y, Lin M, Liu G, Yao M, Liao Q, Xie Z. A strategy for the targeted metabolomics analysis of 11 gut microbiota-host co-metabolites in rat serum, urine and feces by ultra high performance liquid chromatography-tandem mass spectrometry. J Chromatogr A 2015; 1429:207-17. [PMID: 26733392 DOI: 10.1016/j.chroma.2015.12.031] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 11/27/2015] [Accepted: 12/10/2015] [Indexed: 02/06/2023]
Abstract
Microbiota-host co-metabolites are well-known to play important physiological roles, and their dysregulation has been found to be closely related to various diseases, including but not limited to inflammatory disorders. We developed herein an original and feasible method using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method developed enables rapid quantification of 11 key gut microbiota-host co-metabolites spanning the succinate, phenylacetylglutamine, hippurate and trimethylamine metabolic pathways within 10 min. With this method, we were able to simultaneously monitor inflammation-induced alterations of these metabolites in rat serum, urine and feces matrices. The measured levels for this panel of endogenous metabolites ranged from 0.001 to 172.8 μg m L(-1). The intra- and inter-day precision of three analytes was less than 13.1% and the accuracy was between -13.0 to 11.2% for all QC levels. The extraction recoveries in serum ranged from 85.4 to 103.2%, while the RSD was 9.0% or less for all recoveries. In addition, extraction recoveries of 11 analytes in urine and feces samples were between 85.7% and 102.0% and RSD was less than 9.5%. The method developed here has been successfully applied to the analysis of real samples from 2,4,6-trinitrobenzenesulfonic acid-induced Crohn's disease in rats. All of these results suggest that the presently developed method is sufficiently sensitive and robust to simultaneously monitor co-metabolites with diverse properties and a range of different concentrations. Therefore, this method will be expected to be useful for comprehensive studies of the pathophysiological roles and mechanisms of these key microbiota-host co-metabolites, which reflect the function of the intestine, consequently offering novel opportunities for evaluating the occurrence, development and therapeutic effects of diseases related to microbiota disturbances.
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Affiliation(s)
- Waner Hou
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; College of Chinese Traditional Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Danmin Zhong
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Peiting Zhang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Yemeng Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Manna Lin
- College of Chinese Traditional Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Guanghui Liu
- College of Chinese Traditional Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Meicun Yao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Qiongfeng Liao
- College of Chinese Traditional Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
| | - Zhiyong Xie
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
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Liesenfeld DB, Habermann N, Toth R, Owen RW, Frei E, Staffa J, Schrotz-King P, Klika KD, Ulrich CM. Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare). Metabolomics 2015; 11:998-1012. [PMID: 29250455 PMCID: PMC5730072 DOI: 10.1007/s11306-014-0758-3] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Metabolomics is a valuable tool for biomarker screening of colorectal cancer (CRC). In this study, we profiled the urinary metabolomes of patients enrolled in a prospective patient cohort (ColoCare). We aimed to describe changes in the metabolome in the longer clinical follow-up and describe initial predictors as candidate markers with possibly prognostic significance. METHODS In total, 199 urine samples from CRC patients pre-surgery (n=97), 1-8 days post-surgery (n=12) and then after 6 and 12 months (n=52 and 38, respectively) were analyzed using both GC-MS and 1H-NMR. Both datasets were analyzed separately with built in uni- and multivariate analyses of Metaboanalyst 2.0. Furthermore, adjusted linear mixed effects regression models were constructed. RESULTS Many concentrations of the metabolites derived from the gut microbiome were affected by CRC surgery, presumably indicating a tumor-induced shift in bacterial species. Associations of the microbial metabolites with disease stage indicate an important role of the gut microbiome in CRC.We were able to differentiate the metabolite profiles of CRC patients prior to surgery from those at any post-surgery timepoint using a multivariate model containing 20 marker metabolites (AUCROC=0.89; 95% CI:0.84-0.95). CONCLUSION To the best of our knowledge, this is one of the first metabolomic studies to follow CRC patients in a prospective setting with repeated urine sampling over time. We were able to confirm markers initially identified in case-control studies and pin point metabolites which may serve as candidates for prognostic biomarkers of CRC.
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Affiliation(s)
- David B. Liesenfeld
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK)
| | - Nina Habermann
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK)
| | - Reka Toth
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK)
| | - Robert W. Owen
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK)
| | - Eva Frei
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK)
| | - Jürgen Staffa
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK)
| | - Petra Schrotz-King
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK)
| | - Karel D. Klika
- Genomics and Proteomics Core Facility, Molecular Structure Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Cornelia M. Ulrich
- Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK)
- Fred Hutchinson Cancer Research Center (FHCRC), Seattle, Washington
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Zhu WN, Long HY. Application of metabonomics in research of inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2015; 23:2084-2090. [DOI: 10.11569/wcjd.v23.i13.2084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic non-specific inflammatory disorder of the gastrointestinal tract. The etiology and pathogenesis of IBD are still not entirely understood today and are thought to be caused by the interaction of multiple factors, including environmental, genetic, infectious and immune factors. The lack of typical clinical features also leads to a difficult diagnosis of IBD. In recent years, metabonomics is becoming a very important way to find biomarkers and investigate disease mechanisms. In this paper we review the main technologies of metabonomics and their present application in IBD.
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Application of metabolomics in autoimmune diseases: Insight into biomarkers and pathology. J Neuroimmunol 2015; 279:25-32. [DOI: 10.1016/j.jneuroim.2015.01.001] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 10/09/2014] [Accepted: 01/05/2015] [Indexed: 12/31/2022]
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Xu X, Cheng S, Ding C, Lv Z, Chen D, Wu J, Zheng S. Identification of bile biomarkers of biliary tract cancer through a liquid chromatography/mass spectrometry-based metabolomic method. Mol Med Rep 2014; 11:2191-8. [PMID: 25405977 DOI: 10.3892/mmr.2014.2973] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Accepted: 10/24/2014] [Indexed: 02/05/2023] Open
Abstract
The incidence and mortality rate of biliary tract cancer have been increasing worldwide; however, its diagnosis and prognosis have not improved in recent years. A novel approach, termed 'metabolomics', may have the potential to be developed as an effective diagnostic tool. The present study prospectively obtained bile samples from 115 individuals, including 32 patients with biliary tract cancer, 61 patients with benign biliary tract diseases and 22 normal controls. A liquid chromatography/mass spectrometry (LC/MS)‑based approach was used to investigate the differences in bile samples between the three groups, followed by multivariate statistical analysis, which included partial least squares projection to latent structures with discriminant analysis (PLS‑DA) and orthogonal projection to latent structures with discriminant analysis (OPLS‑DA). The metabolomic 2D score plot and 3D plot revealed clear separation between the cancer, benign and normal control groups by PLS‑DA. To further address the significant difficulties in clinically differentiating between biliary tract cancer and benign biliary tract diseases, OPLS‑DA was performed to distinguish between the two disease groups and to select potential biomarkers. The cancer and benign groups were well differentiated. The metabolic analysis revealed significantly lower levels of lysophosphatidylcholine, phenylalanine, 2‑octenoylcarnitine, tryptophan and significantly higher levels of taurine‑ and glycine‑conjugated bile acids in the bile from patients with biliary tract cancer compared with those in the bile from patients with benign biliary tract disease. The present study suggested that an LC/MS‑based metabolomic investigation provides a potent and promising approach for discriminating biliary tract cancer from benign biliary tract diseases and the identified specific metabolites may offer potential as novel biomarkers for the early detection of biliary tract cancer.
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Affiliation(s)
- Xiaofeng Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Shaobing Cheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Chaofeng Ding
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Zhen Lv
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Deying Chen
- Collaborative Innovation Center of Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, P.R. China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
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Li P, Cui BT, Duan YN, Zhang FM. Laboratory evaluation and metabolomics in inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2014; 22:3592-3599. [DOI: 10.11569/wcjd.v22.i24.3592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Diagnosis and prognosis of inflammatory bowel disease (IBD) remain a challenge for physicians, and they are often based on history, clinical symptoms and endoscopic, histological, radiological and laboratory findings. Studies have shown that metabolomics may have important value in the diagnosis and prognosis of IBD. This paper will review the latest progress in laboratory evaluation and metabolomics in IBD.
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40
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Dou CZ, Feng H, Zheng X, Liu XX, Zhu XF, Liu SM, Wu LY, Yang L, Lu Y, Zhang WW, Liu HR. Thinking on functional mechanism of acupuncture for inflammatory bowel diseases based on Metabolomics. JOURNAL OF ACUPUNCTURE AND TUINA SCIENCE 2014. [DOI: 10.1007/s11726-014-0751-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Steelman SM, Johnson P, Jackson A, Schulze J, Chowdhary BP. Serum metabolomics identifies citrulline as a predictor of adverse outcomes in an equine model of gut-derived sepsis. Physiol Genomics 2014; 46:339-47. [PMID: 24619519 DOI: 10.1152/physiolgenomics.00180.2013] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the Lmn group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in Lmn samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis.
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Affiliation(s)
- Samantha M Steelman
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas;
| | - Philip Johnson
- Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri; and
| | - Amy Jackson
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas
| | | | - Bhanu P Chowdhary
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas
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Hartwell SK, Kehling A, Lapanantnoppakhun S, Grudpan K. Flow Injection/Sequential Injection Chromatography: A Review of Recent Developments in Low Pressure with High Performance Chemical Separation. ANAL LETT 2013. [DOI: 10.1080/00032719.2012.749487] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Abstract
PURPOSE OF REVIEW The assessment of metabolite profiles in biofluids has become a powerful method for the detection of biomarker molecules and disease mechanisms. This review outlines the recent advances in the use of metabolomic techniques to study inflammatory bowel diseases (IBDs). RECENT FINDINGS The last few years have seen an increase in the studies of experimental and human IBD focusing on the search for small metabolites, such as amino acids, bases, and tricarboxylic acid cycle intermediates. Experimental methods for the screening of metabolites in serum, urine, fecal extracts, and colon tissue include H NMR spectroscopy, gas chromatography-mass spectrometry, and liquid chromatography methods. Several studies demonstrate that IBD patients and healthy individuals, as well as the IBD subtypes, can be distinguished using metabolic profiling. Metabolomic data of fecal extracts and urine have revealed disruptions in bacterial populations, findings that are indicative of a possible involvement of the microbiome in the development of IBDs. SUMMARY Metabolites from biofluids can be detected in IBDs by different experimental methods that allow successful separation of IBD subtypes from healthy cohorts. Knowledge of a unique metabolomic fingerprint in IBDs could be useful for diagnosis, treatment, and detection of disease mechanisms.
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Denoroy L, Zimmer L, Renaud B, Parrot S. Ultra high performance liquid chromatography as a tool for the discovery and the analysis of biomarkers of diseases: A review. J Chromatogr B Analyt Technol Biomed Life Sci 2013; 927:37-53. [DOI: 10.1016/j.jchromb.2012.12.005] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2012] [Revised: 12/06/2012] [Accepted: 12/07/2012] [Indexed: 12/25/2022]
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Corominas-Faja B, Quirantes-Piné R, Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Martin-Castillo B, Micol V, Joven J, Segura-Carretero A, Menendez JA. Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs. Aging (Albany NY) 2012; 4:480-98. [PMID: 22837425 PMCID: PMC3433934 DOI: 10.18632/aging.100472] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Metabolomic fingerprint of breast cancer cells treated with the antidiabetic drug metformin revealed a significant accumulation of 5-formimino-tetrahydrofolate, one of the tetrahydrofolate forms carrying activated one-carbon units that are essential for the de novo synthesis of purines and pyrimidines. De novo synthesis of glutathione, a folate-dependent pathway interconnected with one-carbon metabolism was concomitantly depleted in response to metformin. End-product reversal studies demonstrated that thymidine alone leads to a significant but incomplete protection from metformin's cytostatic effects. The addition of the substrate hypoxanthine for the purine salvage pathway produces major rightward shifts in metformin's growth inhibition curves. Metformin treatment failed to activate the DNA repair protein ATM kinase and the metabolic tumor suppressor AMPK when thymidine and hypoxanthine were present in the extracellular milieu. Our current findings suggest for the first time that metformin can function as an antifolate chemotherapeutic agent that induces the ATM/AMPK tumor suppressor axis secondarily following the alteration of the carbon flow through the folate-related one-carbon metabolic pathways.
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