請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81996完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭錦樺(Ching-Hua Kuo) | |
| dc.contributor.author | Hsin-Yu Liao | en |
| dc.contributor.author | 廖馨瑜 | zh_TW |
| dc.date.accessioned | 2022-11-25T05:33:47Z | - |
| dc.date.available | 2024-08-25 | |
| dc.date.copyright | 2021-09-16 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-25 | |
| dc.identifier.citation | 1.Lavelle, A.; Sokol, H., Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 2020, 17 (4), 223–237. 2.Caspani, G.; Kennedy, S.; Foster, J. A.; Swann, J., Gut microbial metabolites in depression: understanding the biochemical mechanisms. Microb. Cell 2019, 6 (10), 454–481. 3.Agus, A.; Planchais, J.; Sokol, H., Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe 2018, 23 (6), 716–724. 4.Witkowski, M.; Weeks Taylor, L.; Hazen Stanley, L., Gut microbiota and cardiovascular disease. Circ. Res. 2020, 127 (4), 553–570. 5.Brown, J. M.; Hazen, S. L., Microbial modulation of cardiovascular disease. Nat. Rev. Microbiol. 2018, 16 (3), 171–181. 6.Nemet, I.; Saha, P. P.; Gupta, N.; Zhu, W.; Romano, K. A.; Skye, S. M.; Cajka, T.; Mohan, M. L.; Li, L.; Wu, Y.; Funabashi, M.; Ramer-Tait, A. E.; Naga Prasad, S. V.; Fiehn, O.; Rey, F. E.; Tang, W. H. W.; Fischbach, M. A.; DiDonato, J. A.; Hazen, S. L., A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors. Cell 2020, 180 (5), 862-877.e22. 7.Khurana, S.; Raufman, J.-P.; Pallone, T. L., Bile acids regulate cardiovascular function. Clin. Transl. Sci. 2011, 4 (3), 210–218. 8.Koh, A.; De Vadder, F.; Kovatcheva-Datchary, P.; Bäckhed, F., From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell 2016, 165 (6), 1332–1345. 9.Whelton, S. P.; Hyre, A. D.; Pedersen, B.; Yi, Y.; Whelton, P. K.; He, J., Effect of dietary fiber intake on blood pressure: a meta-analysis of randomized, controlled clinical trials. J. Hypertens. 2005, 23 (3), 475–481. 10.Zhang, Z.; Tang, H.; Chen, P.; Xie, H.; Tao, Y., Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome. Signal Transduct. Target. Ther. 2019, 4 (1), 41. 11.Zhao, Z.-H.; Xin, F.-Z.; Xue, Y.; Hu, Z.; Han, Y.; Ma, F.; Zhou, D.; Liu, X.-L.; Cui, A.; Liu, Z.; Liu, Y.; Gao, J.; Pan, Q.; Li, Y.; Fan, J.-G., Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats. Exp. Mol. Med. 2019, 51 (9), 1–14. 12.Müller, M.; Hernández, M. A. G.; Goossens, G. H.; Reijnders, D.; Holst, J. J.; Jocken, J. W. E.; van Eijk, H.; Canfora, E. E.; Blaak, E. E., Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans. Sci. Rep. 2019, 9 (1), 12515. 13.Ahmad, T. R.; Haeusler, R. A., Bile acids in glucose metabolism and insulin signalling — mechanisms and research needs. Nat. Rev. Endocrinol. 2019, 15 (12), 701–712. 14.Cariou, B.; Chetiveaux, M.; Zaïr, Y.; Pouteau, E.; Disse, E.; Guyomarc'h-Delasalle, B.; Laville, M.; Krempf, M., Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults. Nutr. Metab. 2011, 8 (1), 48. 15.Cirstea, M. S.; Yu, A. C.; Golz, E.; Sundvick, K.; Kliger, D.; Radisavljevic, N.; Foulger, L. H.; Mackenzie, M.; Huan, T.; Finlay, B. B.; Appel-Cresswell, S., Microbiota composition and metabolism are associated with gut function in parkinson's disease. Mov. Disord. 2020, 35 (7), 1208–1217. 16.Pan, X.; Wen, S. W.; Kaminga, A. C.; Liu, A., Gut metabolites and inflammation factors in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Sci. Rep. 2020, 10 (1), 8848. 17.Ragonnaud, E.; Biragyn, A., Gut microbiota as the key controllers of 'healthy' aging of elderly people. Immun. Ageing 2021, 18 (1), 2. 18.Zhang, S.; Wang, H.; Zhu, M. J., A sensitive GC/MS detection method for analyzing microbial metabolites short chain fatty acids in fecal and serum samples. Talanta 2019, 196, 249–254. 19.Hsu, Y. L.; Chen, C. C.; Lin, Y. T.; Wu, W. K.; Chang, L. C.; Lai, C. H.; Wu, M. S.; Kuo, C. H., Evaluation and optimization of sample handling methods for quantification of short-chain fatty acids in human fecal samples by GC-MS. J. Proteome Res. 2019, 18 (5), 1948–1957. 20.Hoving, L. R.; Heijink, M.; van Harmelen, V.; van Dijk, K. W.; Giera, M., GC-MS analysis of short-chain fatty acids in feces, cecum content, and blood samples. Methods Mol. Biol. 2018, 1730, 247–256. 21.Choucair, I.; Nemet, I.; Li, L.; Cole, M. A.; Skye, S. M.; Kirsop, J. D.; Fischbach, M. A.; Gogonea, V.; Brown, J. M.; Tang, W. H. W.; Hazen, S. L., Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases. J. Lipid Res. 2020, 61 (2), 159–177. 22.Hu, T.; An, Z.; Shi, C.; Li, P.; Liu, L., A sensitive and efficient method for simultaneous profiling of bile acids and fatty acids by UPLC-MS/MS. J. Pharm. Biomed. Anal. 2020, 178, 112815. 23.Sarafian, M. H.; Lewis, M. R.; Pechlivanis, A.; Ralphs, S.; McPhail, M. J.; Patel, V. C.; Dumas, M. E.; Holmes, E.; Nicholson, J. K., Bile acid profiling and quantification in biofluids using ultra-performance liquid chromatography tandem mass spectrometry. Anal. Chem. 2015, 87 (19), 9662–9670. 24.Chen, Y.; Chen, H.; Shi, G.; Yang, M.; Zheng, F.; Zheng, Z.; Zhang, S.; Zhong, S., Ultra-performance liquid chromatography-tandem mass spectrometry quantitative profiling of tryptophan metabolites in human plasma and its application to clinical study. J. Chromatogr. B 2019, 1128, 121745. 25.Zou, B.; Sun, Y.; Xu, Z.; Chen, Y.; Li, L.; Lin, L.; Zhang, S.; Liao, Q.; Xie, Z., Rapid simultaneous determination of gut microbial phenylalanine, tyrosine, and tryptophan metabolites in rat serum, urine, and faeces using LC–MS/MS and its application to a type 2 diabetes mellitus study. Biomed. Chromatogr. 2020, e4985. 26.Higashi, T.; Watanabe, S.; Tomaru, K.; Yamazaki, W.; Yoshizawa, K.; Ogawa, S.; Nagao, H.; Minato, K.; Maekawa, M.; Mano, N., Unconjugated bile acids in rat brain: Analytical method based on LC/ESI-MS/MS with chemical derivatization and estimation of their origin by comparison to serum levels. Steroids 2017, 125, 107–113. 27.Han, J.; Liu, Y.; Wang, R.; Yang, J.; Ling, V.; Borchers, C. H., Metabolic profiling of bile acids in human and mouse blood by LC–MS/MS in combination with phospholipid-depletion solid-phase extraction. Anal. Chem. 2015, 87 (2), 1127–1136. 28.Sadok, I.; Gamian, A.; Staniszewska, M. M., Chromatographic analysis of tryptophan metabolites. J. Sep. Sci. 2017, 40 (15), 3020–3045. 29.Han, J.; Lin, K.; Sequeira, C.; Borchers, C. H., An isotope-labeled chemical derivatization method for the quantitation of short-chain fatty acids in human feces by liquid chromatography-tandem mass spectrometry. Anal. Chim. Acta 2015, 854, 86–94. 30.Benjamini, Y.; Hochberg, Y., Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B-Stat. Methodol. 1995, 57 (1), 289–300. 31.Zeng, M.; Cao, H., Fast quantification of short chain fatty acids and ketone bodies by liquid chromatography-tandem mass spectrometry after facile derivatization coupled with liquid-liquid extraction. J. Chromatogr. B 2018, 1083, 137–145. 32.Kanemitsu, Y.; Mishima, E.; Maekawa, M.; Matsumoto, Y.; Saigusa, D.; Yamaguchi, H.; Ogura, J.; Tsukamoto, H.; Tomioka, Y.; Abe, T.; Mano, N., Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS. Sci. Rep. 2019, 9 (1), 19075. 33.U.S. Department of Health and Human Services Food and Drug Administration; Center for Drug Evaluation and Research (CDER); Center for Veterinary Medicine (CVM). Bioanalytical Method Validation-Guidance for Industry. 2018. 34.Sonne, D. P.; van Nierop, F. S.; Kulik, W.; Soeters, M. R.; Vilsbøll, T.; Knop, F. K., Postprandial plasma concentrations of individual bile acids and FGF-19 in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 2016, 101 (8), 3002–3009. 35.Jie, Z.; Xia, H.; Zhong, S.-L.; Feng, Q.; Li, S.; Liang, S.; Zhong, H.; Liu, Z.; Gao, Y.; Zhao, H.; Zhang, D.; Su, Z.; Fang, Z.; Lan, Z.; Li, J.; Xiao, L.; Li, J.; Li, R.; Li, X.; Li, F.; Ren, H.; Huang, Y.; Peng, Y.; Li, G.; Wen, B.; Dong, B.; Chen, J.-Y.; Geng, Q.-S.; Zhang, Z.-W.; Yang, H.; Wang, J.; Wang, J.; Zhang, X.; Madsen, L.; Brix, S.; Ning, G.; Xu, X.; Liu, X.; Hou, Y.; Jia, H.; He, K.; Kristiansen, K., The gut microbiome in atherosclerotic cardiovascular disease. Nat. Commun. 2017, 8 (1), 845. 36.Karlsson, F. H.; Fåk, F.; Nookaew, I.; Tremaroli, V.; Fagerberg, B.; Petranovic, D.; Bäckhed, F.; Nielsen, J., Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat. Commun. 2012, 3 (1), 1245. 37.Kasahara, K.; Krautkramer, K. A.; Org, E.; Romano, K. A.; Kerby, R. L.; Vivas, E. I.; Mehrabian, M.; Denu, J. M.; Bäckhed, F.; Lusis, A. J.; Rey, F. E., Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model. Nat. Microbiol. 2018, 3 (12), 1461–1471. 38.Tang, J.; Li, Y.; Huang, X.; He, L.; Zhang, L.; Wang, H.; Yu, W.; Pu, W.; Tian, X.; Nie, Y.; Hu, S.; Wang, Q. D.; Lui, K. O.; Zhou, B., Fate mapping of Sca1(+) cardiac progenitor cells in the adult mouse heart. Circulation 2018, 138 (25), 2967–2969. 39.Tang Tony, W. H.; Chen, H.-C.; Chen, C.-Y.; Yen Christopher, Y. T.; Lin, C.-J.; Prajnamitra Ray, P.; Chen, L.-L.; Ruan, S.-C.; Lin, J.-H.; Lin, P.-J.; Lu, H.-H.; Kuo, C.-W.; Chang Cindy, M.; Hall Alexander, D.; Vivas Eugenio, I.; Shui, J.-W.; Chen, P.; Hacker Timothy, A.; Rey Federico, E.; Kamp Timothy, J.; Hsieh Patrick, C. H., Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation 2019, 139 (5), 647–659. 40.Cleophas, M. C. P.; Ratter, J. M.; Bekkering, S.; Quintin, J.; Schraa, K.; Stroes, E. S.; Netea, M. G.; Joosten, L. A. B., Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males. Sci. Rep. 2019, 9 (1), 775. 41.Krautkramer, K. A.; Fan, J.; Bäckhed, F., Gut microbial metabolites as multi-kingdom intermediates. Nat. Rev. Microbiol. 2020. 42.Fan, Y.; Pedersen, O., Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol. 2021, 19 (1), 55–71. 43.Metghalchi, S.; Ponnuswamy, P.; Simon, T.; Haddad, Y.; Laurans, L.; Clément, M.; Dalloz, M.; Romain, M.; Esposito, B.; Koropoulis, V.; Lamas, B.; Paul, J. L.; Cottin, Y.; Kotti, S.; Bruneval, P.; Callebert, J.; den Ruijter, H.; Launay, J. M.; Danchin, N.; Sokol, H.; Tedgui, A.; Taleb, S.; Mallat, Z., Indoleamine 2,3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production. Cell Metab. 2015, 22 (3), 460-71. 44.Platten, M.; Nollen, E. A. A.; Röhrig, U. F.; Fallarino, F.; Opitz, C. A., Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat. Rev. Drug Discov. 2019, 18 (5), 379–401. 45.Roager, H. M.; Licht, T. R., Microbial tryptophan catabolites in health and disease. Nat. Commun. 2018, 9 (1), 3294. 46.Taleb, S., Tryptophan Dietary Impacts Gut Barrier and Metabolic Diseases. Front. Immunol. 2019, 10, 2113. 47.Hendrikx, T.; Schnabl, B., Indoles: metabolites produced by intestinal bacteria capable of controlling liver disease manifestation. J. Intern. Med. 2019, 286 (1), 32–40. 48.Shafi, T.; Meyer, T. W.; Hostetter, T. H.; Melamed, M. L.; Parekh, R. S.; Hwang, S.; Banerjee, T.; Coresh, J.; Powe, N. R., Free levels of selected organic solutes and cardiovascular morbidity and mortality in hemodialysis patients: Results from the retained organic solutes and clinical outcomes (ROSCO) Investigators. PLoS One 2015, 10 (5), e0126048. 49.Huang, M.; Wei, R.; Wang, Y.; Su, T.; Li, P.; Chen, X., The uremic toxin hippurate promotes endothelial dysfunction via the activation of Drp1-mediated mitochondrial fission. Redox. Biol. 2018, 16, 303–313. 50.Wu, W. K.; Chen, C. C.; Liu, P. Y.; Panyod, S.; Liao, B. Y.; Chen, P. C.; Kao, H. L.; Kuo, H. C.; Kuo, C. H.; Chiu, T. H. T.; Chen, R. A.; Chuang, H. L.; Huang, Y. T.; Zou, H. B.; Hsu, C. C.; Chang, T. Y.; Lin, C. L.; Ho, C. T.; Yu, H. T.; Sheen, L. Y.; Wu, M. S., Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice. Gut 2019, 68 (8), 1439-1449. 51.Liu, Y.; Hou, Y.; Wang, G.; Zheng, X.; Hao, H., Gut Microbial Metabolites of Aromatic Amino Acids as Signals in Host-Microbe Interplay. Trends Endocrinol. Metab. 2020, 31 (11), 818-834. 52.Roiser, J. P.; McLean, A.; Ogilvie, A. D.; Blackwell, A. D.; Bamber, D. J.; Goodyer, I.; Jones, P. B.; Sahakian, B. J., The Subjective and Cognitive Effects of Acute Phenylalanine and Tyrosine Depletion in Patients Recovered from Depression. Neuropsychopharmacology 2005, 30 (4), 775-785. 53.Cui, Y.; Cao, K.; Lin, H.; Cui, S.; Shen, C.; Wen, W.; Mo, H.; Dong, Z.; Bai, S.; Yang, L.; Shi, Y.; Zhang, R., Early-Life Stress Induces Depression-Like Behavior and Synaptic-Plasticity Changes in a Maternal Separation Rat Model: Gender Difference and Metabolomics Study. Front. Pharmacol. 2020, 11, 102. 54.Kofler, M.; Schiefecker, A. J.; Gaasch, M.; Sperner-Unterweger, B.; Fuchs, D.; Beer, R.; Ferger, B.; Rass, V.; Hackl, W.; Rhomberg, P.; Pfausler, B.; Thomé, C.; Schmutzhard, E.; Helbok, R., A reduced concentration of brain interstitial amino acids is associated with depression in subarachnoid hemorrhage patients. Sci. Rep. 2019, 9 (1), 2811. 55.Dodd, D.; Spitzer, M. H.; Van Treuren, W.; Merrill, B. D.; Hryckowian, A. J.; Higginbottom, S. K.; Le, A.; Cowan, T. M.; Nolan, G. P.; Fischbach, M. A.; Sonnenburg, J. L., A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature 2017, 551 (7682), 648-652. 56.Guo, C. J.; Allen, B. M.; Hiam, K. J.; Dodd, D.; Van Treuren, W.; Higginbottom, S.; Nagashima, K.; Fischer, C. R.; Sonnenburg, J. L.; Spitzer, M. H.; Fischbach, M. A., Depletion of microbiome-derived molecules in the host using Clostridium genetics. Science 2019, 366 (6471). 57.Poesen, R.; Claes, K.; Evenepoel, P.; de Loor, H.; Augustijns, P.; Kuypers, D.; Meijers, B., Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKD. J. Am. Soc. Nephrol. 2016, 27 (11), 3479-3487. 58.Bogiatzi, C.; Gloor, G.; Allen-Vercoe, E.; Reid, G.; Wong, R. G.; Urquhart, B. L.; Dinculescu, V.; Ruetz, K. N.; Velenosi, T. J.; Pignanelli, M.; Spence, J. D., Metabolic products of the intestinal microbiome and extremes of atherosclerosis. Atherosclerosis 2018, 273, 91-97. 59.Ottosson, F.; Brunkwall, L.; Smith, E.; Orho-Melander, M.; Nilsson, P. M.; Fernandez, C.; Melander, O., The gut microbiota-related metabolite phenylacetylglutamine associates with increased risk of incident coronary artery disease. J. Hypertens. 2020, 38 (12), 2427-2434. 60.Tang, H. Y.; Wang, C. H.; Ho, H. Y.; Lin, J. F.; Lo, C. J.; Huang, C. Y.; Cheng, M. L., Characteristic of Metabolic Status in Heart Failure and Its Impact in Outcome Perspective. Metabolites 2020, 10 (11). 61.Liao, H. Y.; Wang, C. Y.; Lee, C. H.; Kao, H. L.; Wu, W. K.; Kuo, C. H., Development of an Efficient and Sensitive Chemical Derivatization-Based LC-MS/MS Method for Quantifying Gut Microbiota-Derived Metabolites in Human Plasma and Its Application in Studying Cardiovascular Disease. J. Proteome Res. 2021. 62.Wu, W. K.; Panyod, S.; Liu, P. Y.; Chen, C. C.; Kao, H. L.; Chuang, H. L.; Chen, Y. H.; Zou, H. B.; Kuo, H. C.; Kuo, C. H.; Liao, B. Y.; Chiu, T. H. T.; Chung, C. H.; Lin, A. Y.; Lee, Y. C.; Tang, S. L.; Wang, J. T.; Wu, Y. W.; Hsu, C. C.; Sheen, L. Y.; Orekhov, A. N.; Wu, M. S., Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery. Microbiome 2020, 8 (1), 162. 63.Chiu, T. H.; Huang, H. Y.; Chen, K. J.; Wu, Y. R.; Chiu, J. P.; Li, Y. H.; Chiu, B. C.; Lin, C. L.; Lin, M. N., Relative validity and reproducibility of a quantitative FFQ for assessing nutrient intakes of vegetarians in Taiwan. Public Health Nutr. 2014, 17 (7), 1459-66. 64.Hu, F. B.; Stampfer, M. J.; Manson, J. E.; Ascherio, A.; Colditz, G. A.; Speizer, F. E.; Hennekens, C. H.; Willett, W. C., Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women. Am. J. Clin. Nutr. 1999, 70 (6), 1001-8. 65.Zong, G.; Li, Y.; Wanders, A. J.; Alssema, M.; Zock, P. L.; Willett, W. C.; Hu, F. B.; Sun, Q., Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: two prospective longitudinal cohort studies. BMJ 2016, 355, i5796. 66.Cui, L.; Zhao, T.; Hu, H.; Zhang, W.; Hua, X., Association Study of Gut Flora in Coronary Heart Disease through High-Throughput Sequencing. BioMed research international 2017, 2017, 3796359. 67.Zuo, K.; Li, J.; Xu, Q.; Hu, C.; Gao, Y.; Chen, M.; Hu, R.; Liu, Y.; Chi, H.; Yin, Q.; Cao, Y.; Wang, P.; Qin, Y.; Liu, X.; Zhong, J.; Cai, J.; Li, K.; Yang, X., Dysbiotic gut microbes may contribute to hypertension by limiting vitamin D production. Clin. Cardiol. 2019, 42 (8), 710-719. 68.Van Hul, M.; Le Roy, T.; Prifti, E.; Dao, M. C.; Paquot, A.; Zucker, J. D.; Delzenne, N. M.; Muccioli, G.; Clément, K.; Cani, P. D., From correlation to causality: the case of Subdoligranulum. Gut microbes 2020, 12 (1), 1-13. 69.Aron-Wisnewsky, J.; Vigliotti, C.; Witjes, J.; Le, P.; Holleboom, A. G.; Verheij, J.; Nieuwdorp, M.; Clément, K., Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders. Nature Reviews Gastroenterology Hepatology 2020, 17 (5), 279-297. 70.Louis, S.; Tappu, R. M.; Damms-Machado, A.; Huson, D. H.; Bischoff, S. C., Characterization of the Gut Microbial Community of Obese Patients Following a Weight-Loss Intervention Using Whole Metagenome Shotgun Sequencing. PLoS One 2016, 11 (2), e0149564. 71.Aryal, S.; Alimadadi, A.; Manandhar, I.; Joe, B.; Cheng, X., Machine Learning Strategy for Gut Microbiome-Based Diagnostic Screening of Cardiovascular Disease. Hypertension 2020, 76 (5), 1555-1562. 72.Hammad, S.; Pu, S.; Jones, P. J., Current Evidence Supporting the Link Between Dietary Fatty Acids and Cardiovascular Disease. Lipids 2016, 51 (5), 507-17. 73.Kien, C. L.; Bunn, J. Y.; Stevens, R.; Bain, J.; Ikayeva, O.; Crain, K.; Koves, T. R.; Muoio, D. M., Dietary intake of palmitate and oleate has broad impact on systemic and tissue lipid profiles in humans. Am. J. Clin. Nutr. 2014, 99 (3), 436-45. 74.Schwingshackl, L.; Strasser, B.; Hoffmann, G., Effects of monounsaturated fatty acids on cardiovascular risk factors: a systematic review and meta-analysis. Ann. Nutr. Metab. 2011, 59 (2-4), 176-86. 75.Gillingham, L. G.; Harris-Janz, S.; Jones, P. J., Dietary monounsaturated fatty acids are protective against metabolic syndrome and cardiovascular disease risk factors. Lipids 2011, 46 (3), 209-28. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81996 | - |
| dc.description.abstract | "人體內的微生物是由細菌和真菌群落所組成，複雜度更甚於人體之基因。與相對恆定的人類基因不同，人體的微生物組成是相對動態的，會隨著飲食、使用的抗生素和生活方式等許多因素而變化。有越來越多的研究顯示，人類的腸道微生物可以藉由其代謝物調節宿主免疫、防禦病原體並影響宿主的心理或行為。這些腸道菌代謝物（Gut microbiota-derived metabolites, GMs）不僅存在於腸道中，還存在於宿主循環中。而循環系統裡的GMs在許多疾病進展中常常扮演著重要的角色。 在本論文的第一部分，我們開發了一種使用液相層析串聯式質譜儀(Liquid Chromatography Tandem Mass Spectrometry, LC-MS/MS) 廣泛定量人體血漿內的GMs。在各種 GMs 中，短鏈脂肪酸 (Short-chain fatty acids, SCFAs)、膽酸 (Bile acids, BAs) 和芳香族胺基酸 (Aromatic amino acids, AAAs) 及其代謝物是最常被討論的。在本研究中，我們開發同時分析 SCFAs、BAs 和色氨酸 (Tryptophan, TRP) 代謝物的方法。 LC-MS/MS 在定量上具有良好的靈敏度和選擇性，然而，SCFAs游離化效率差、具高極性等問題皆增加其用LC-MS/MS進行分析的困難度，尤其當需要分析血中低濃度的SCFAs。此外，在串聯質譜儀上不易有非共軛膽酸的特徵碎片離子且TRP和其代謝物與膽酸需在不同離子模式下被偵測，這些問題，都使得GMs分析既複雜又耗時。為了克服這些問題，我們開發了一種結合 LC-MS/MS 的衍生化方法，以提高偵測GMs的靈敏度和增加代謝物在管柱上的滯留。藉由 3-硝基苯肼 (3- nitrophenylhydrazine, 3-NPH) 進行衍生，以C18管柱分離，7種 SCFAs、9種 BAs和6種TRP代謝物可以在14分鐘完成分析。本研究使用13C6-3NPH 和GMs標準品的衍生物作為一對一的內標，用於準確定量。經過一系列的方法優化和確校，我們進一步應用此方法來探討心血管疾病患者的腸道微生物代謝物組成。這項研究提供了一種靈敏且有效的 LC-MS/MS 方法，可同時定量人血漿中22種腸道微生物代謝物，將有益於未來的腸道微生物之相關研究。 在第二部分，我們提出了一種口服苯丙氨耐量試驗 (Oral phenylalanine challenge test, OPCT) ，結合代謝物、食物頻率和腸道菌分析，來研究宿主-飲食-微生物群與苯丙胺酸(Phenylalanine, PHE)代謝之相互關係。PHE屬於芳香族氨基酸，有兩種由腸道微生物群代謝途徑（還原性和氧化性）。苯乙醯谷氨醯胺（Phenylacetylglutamine, PAGln）是PHE氧化途徑中的代謝物之一，已被報導為CVD的危險因子。本研究應用 OPCT 來研究人體血液中的 PHE 和 PHE代謝物濃度，用以評估標的代謝物之間的相關性。研究結果顯示還原途徑的代謝物與氧化途徑代謝物呈顯著負相關。有趣的是，我們還發現 Defluviitaleaceae_UCG-011 和 Subdoligranulum 的豐度都與PHE氧化代謝顯著正相關，而與PHE還原代謝物呈負相關。本研究另外將受試者分為高PAGln生產者和低PAGln 生產者，結果發現這兩組的腸道微生物群組成不同，高PAGln生產者的Chao1指數更高。飲食習慣分析顯示，高PAGln生產者的SFA (8:0)和SFA (12:0)較高，而低PAGln生產者的MUFA(14:1) 較高。 總結本論文開發了一種同時測量22種GM的分析方法，預計其可被廣泛應用於各種臨床研究；本論文並進一步採用OPCT的策略了解宿主-飲食-微生物的相互關係。 " | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T05:33:47Z (GMT). No. of bitstreams: 1 U0001-2308202110053300.pdf: 4597130 bytes, checksum: 055dd50a56fb056f410bf9b307117ea0 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 誌謝-----------------------------------------------------------------------I 中文摘要------------------------------------------------------------------III Abstract-------------------------------------------------------------------V PartⅠ: Development of a chemical derivatization-based LC-MS/MS method for quantifying gut microbial metabolites--------------------------------------------------1 1. Introduction------------------------------------------------------------2 2. Materials and Methods---------------------------------------------------5 2.1 Chemicals and preparation of stock solutions---------------------------5 2.2 Sample preparation with 3-NPH derivatization---------------------------6 2.3 Isotope-labeled internal standard synthesis----------------------------6 2.4 UHPLC-MS/MS------------------------------------------------------------7 2.5 Method validation------------------------------------------------------8 2.6 Clinical application--------------------------------------------------10 2.7 Data analysis---------------------------------------------------------10 3. Results----------------------------------------------------------------11 3.1 Selection of derivatization reagents----------------------------------11 3.2 Optimization of 3-NPH derivatization reactions------------------------12 3.3 Development of the UHPLC-MS/MS method---------------------------------14 3.4 Validation------------------------------------------------------------15 3.5 Clinical application-------------------------------------------------17 4. Discussion-------------------------------------------------------------18 5. Conclusion-------------------------------------------------------------23 6. Figures----------------------------------------------------------------24 7.Tables------------------------------------------------------------------32 Part Ⅱ: Investigation on gut microbial metabolism of phenylalanine and phenylacetylglutamine production------------------------------------------43 1. Introduction-----------------------------------------------------------44 2. Materials and Methods----------------------------------------------------47 2.1 Chemical materials and stock solutions--------------------------------47 2.2 Subjects recruitment and experiment design----------------------------47 2.3 Sample collection-----------------------------------------------------48 2.4 LC-MS/MS analysis of plasma PHE and its metabolites-------------------49 2.5 LC-MS/MS analysis of PAGln in urine-----------------------------------50 2.6 Gut microbiome analysis-----------------------------------------------51 2.7 Statistical analysis--------------------------------------------------53 3. Results----------------------------------------------------------------54 3.1 Baseline characteristics of the subjects in this study----------------54 3.2 Pharmacokinetics of PHE and its metabolites---------------------------55 3.3 Associations of gut microbial metabolites of PHE in oxidative and reductive pathways------------------------------------------------------------------56 3.4 Characterization of gut microbiome and dietary factors for PAGln productivity --------------------------------------------------------------------------58 3.5 Urine sampling can be an alternative in measuring PAGln level---------60 4. Discussion-------------------------------------------------------------60 5. Conclusion-------------------------------------------------------------64 6. Figures----------------------------------------------------------------65 7. Tables-----------------------------------------------------------------73 References----------------------------------------------------------------76 | |
| dc.language.iso | en | |
| dc.subject | 短鏈脂肪酸 | zh_TW |
| dc.subject | 腸道代謝物 | zh_TW |
| dc.subject | 腸道菌 | zh_TW |
| dc.subject | 口服苯丙胺酸耐量試驗 | zh_TW |
| dc.subject | 苯乙醯谷氨醯胺 | zh_TW |
| dc.subject | 心血管疾病 | zh_TW |
| dc.subject | 液相層析質譜儀 | zh_TW |
| dc.subject | 衍生化 | zh_TW |
| dc.subject | 膽酸 | zh_TW |
| dc.subject | phenylacetylglutamine (PAGln) | en |
| dc.subject | gut microbiota | en |
| dc.subject | oral phenylalanine challenge test | en |
| dc.subject | gut metabolites | en |
| dc.subject | SCFAs | en |
| dc.subject | bile acids | en |
| dc.subject | derivatization | en |
| dc.subject | LC−MS | en |
| dc.subject | cardiovascular disease | en |
| dc.title | 第一部分:開發化學衍生化搭配LC-MS/MS定量腸道菌代謝物的分析方法 第二部分:探討腸道菌代謝苯丙胺酸與苯乙醯谷氨醯胺的生成 | zh_TW |
| dc.title | Part I: Development of a chemical derivatization-based LC-MS/MS method for quantifying gut microbial metabolites Part II: Investigation on gut microbial metabolism of phenylalanine and phenylacetylglutamine production | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 吳偉愷(Wei-Kai Wu) | |
| dc.contributor.oralexamcommittee | 蔡伊琳(Hsin-Tsai Liu),(Chih-Yang Tseng) | |
| dc.subject.keyword | 腸道代謝物,短鏈脂肪酸,膽酸,衍生化,液相層析質譜儀,心血管疾病,苯乙醯谷氨醯胺,口服苯丙胺酸耐量試驗,腸道菌, | zh_TW |
| dc.subject.keyword | gut metabolites,SCFAs,bile acids,derivatization,LC−MS,cardiovascular disease,phenylacetylglutamine (PAGln),oral phenylalanine challenge test,gut microbiota, | en |
| dc.relation.page | 83 | |
| dc.identifier.doi | 10.6342/NTU202102608 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-25 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| dc.date.embargo-lift | 2024-08-25 | - |
| 顯示於系所單位： | 藥學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-2308202110053300.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 4.49 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。