基于GC/TOF-MS技术对流感感染小鼠粪便代谢组学的研究
|
摘要
为了探讨小鼠感染流感病毒后粪便代谢物的变化情况,寻找潜在生物标志物及相关的代谢通路,本研究运用气相色谱-飞行时间质谱联用技术(GC/TOF-MS)检测对照组和病毒组小鼠的粪便。结果显示:在正交偏最小二乘法分析(OPLS)模型中,对照组与病毒组的得分图呈现明显差异,病毒组中一些代谢物发生了显著性的改变。α-酮戊二酸、甲硫氨酸、果糖-6-磷酸、苯丙氨酸、草酸、乳糖、棕榈酸、正缬氨酸、腺嘌呤、胆固醇、葡萄糖-6-磷酸、油酸、甘油、十五烷酸、β-丙氨酸等代谢物显著降低,而L-苹果酸、天冬氨酸、乳酸等代谢物显著上升。结论:病毒组与对照组之间存在脂类代谢、氨基酸代谢及糖代谢的差异,代谢组学的研究可以为流感病毒引起的肠道损伤机制提供新的依据。
In this study, we analyzed the metabolite of feces from normal and influenza infected mice to find the potential biomarkers and related metabolic pathways. The fecal samples from normal and influenza virus infected mice were tested by gas chromatography-time of flight mass spectrometry(GC/TOF-MS). An orthogonal partial least squares analysis(OPLS) model was generated. Based on the identified metabolites, we found significant differences betwen the normal and influenza virus infected groups of mice. Some feces metabolite levels were significantly altered in the influenza virus-infected group. Significant down-regulations were observed of alpha-ketoglutaric acid, methionine, fructose-6-phosphate, phenylalanine, oxalic acid, lactose, palmitic acid, norvaline, adenine, cholesterol, glucose-6-phosphate, oleic acid, glycerol, pentadecanoic acid and β-alanine; but significant upregulations were found of L-malic acid, aspartic acid, and lactic acid. To sum up, lipid metabolism, amino acid metabolism and glucose metabolism between the influenza virus-infected group and the normal group were different. The metabolomics approach might offer motivation for understanding the underlying mechanisms of intestinal damage caused by influenza virus.
In this study, we analyzed the metabolite of feces from normal and influenza infected mice to find the potential biomarkers and related metabolic pathways. The fecal samples from normal and influenza virus infected mice were tested by gas chromatography-time of flight mass spectrometry(GC/TOF-MS). An orthogonal partial least squares analysis(OPLS) model was generated. Based on the identified metabolites, we found significant differences betwen the normal and influenza virus infected groups of mice. Some feces metabolite levels were significantly altered in the influenza virus-infected group. Significant down-regulations were observed of alpha-ketoglutaric acid, methionine, fructose-6-phosphate, phenylalanine, oxalic acid, lactose, palmitic acid, norvaline, adenine, cholesterol, glucose-6-phosphate, oleic acid, glycerol, pentadecanoic acid and β-alanine; but significant upregulations were found of L-malic acid, aspartic acid, and lactic acid. To sum up, lipid metabolism, amino acid metabolism and glucose metabolism between the influenza virus-infected group and the normal group were different. The metabolomics approach might offer motivation for understanding the underlying mechanisms of intestinal damage caused by influenza virus.
引文
[1] 周凯, 何宏轩. 禽流感与猪流感病毒:跨越物种传播的新认识[J].生物化学与生物物理进展, 2009,(5):523-529.
[2] Seong-Heon W, Hak S B, Young S J, et al. A comparison of the clinical and epidemiological characteristics of adult patients with laboratory-confirmed influenza A or B during the 2011-2012 influenza season in Korea: a multi-center study[J].PLos One, 2013, 8(5):e62685.
[3] Minodier L, Charrel R N, Ceccaldi P E, et al. Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know[J].Virol J, 2015, 12(1):1-9.
[4] Baden L R, Drazen J M, Kritek P A, et al. H1N1 influenza A disease--information for health professionals[J].New Engl J Med, 2009, 360(25):2666.
[5] Lu H, Zhang C, Qian G, et al. An analysis of microbiota-targeted therapies in patients with avian influenza virus subtype H7N9 infection[J].Bmc Infect Dis, 2014, 14(1):359.
[6] Kostidis S, Kokova D, Dementeva N, et al. 1H-NMR analysis of feces: new possibilities in the helminthes infections research[J].Bms Infect Dis, 2017, 17(1):275.
[7] 赵滢. 抗生素诱导小鼠菌群变化与宿主代谢组相关性的研究[D].武汉:华中科技大学,2013.
[8] 徐旻,林东海,刘昌孝.代谢组学研究现状与展望[J].药学学报,2005(9):769-774.
[9] 李维薇, 杨燕, 汪受传,等. 细胞代谢组学研究进展[J].南京中医药大学学报,2017(2):187-192.
[10] 彭琳秀, 陈良慧, 狄留庆,等. 基于UPLC/LTQ-Orbitrap-MS技术的复方祖师麻片抗类风湿关节炎的血浆代谢组学研究[J].中草药, 2017(10):1964-1970.
[11] Qi Y, Li P, Zhang Y, et al. Urinary metabolite markers of precocious puberty[J].Mol Cell Proteomics,2012,11(1):M111.011072.
[12] Choi S, Shin J H, Lee Y R, et al. Urinary APE1/Ref-1: a potential bladder cancer biomarker[J].Dis Markers, 2016(3):7276502.
[13] Murray D M, Boylan G B, Fitzgerald A P, et al. Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden[J].Arch Dis Child-Fetal, 2008, 93(3):183-186.
[14] Dash P K, Hergenroeder G W, Jeter C B, et al. Traumatic brain injury alters methionine metabolism: implications for pathophysiology[J].Front Neurosci-Switz, 2016,(10):36.
[15] Chen Y, Dong H, Thompson D C, et al. Glutathione defense mechanism in liver injury: Insights from animal models[J].Food Chem Toxicol, 2013, 60(10):38-44.
[16] Dodd D, Spitzer M H, Treuren W V, et al. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites[J].Nature, 2017, 3(10):e00438.
[17] Uchida H, Nakajima Y, Ohtake K, et al. Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress[J].World J Gastroenterol, 2017, 23(36):6650-6664.
[18] Ananthakrishnan A N, Luo C, Yajnik V, et al. Gut microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases.[J].Cell Host Microb, 2017, 21(5):603-610.
[2] Seong-Heon W, Hak S B, Young S J, et al. A comparison of the clinical and epidemiological characteristics of adult patients with laboratory-confirmed influenza A or B during the 2011-2012 influenza season in Korea: a multi-center study[J].PLos One, 2013, 8(5):e62685.
[3] Minodier L, Charrel R N, Ceccaldi P E, et al. Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know[J].Virol J, 2015, 12(1):1-9.
[4] Baden L R, Drazen J M, Kritek P A, et al. H1N1 influenza A disease--information for health professionals[J].New Engl J Med, 2009, 360(25):2666.
[5] Lu H, Zhang C, Qian G, et al. An analysis of microbiota-targeted therapies in patients with avian influenza virus subtype H7N9 infection[J].Bmc Infect Dis, 2014, 14(1):359.
[6] Kostidis S, Kokova D, Dementeva N, et al. 1H-NMR analysis of feces: new possibilities in the helminthes infections research[J].Bms Infect Dis, 2017, 17(1):275.
[7] 赵滢. 抗生素诱导小鼠菌群变化与宿主代谢组相关性的研究[D].武汉:华中科技大学,2013.
[8] 徐旻,林东海,刘昌孝.代谢组学研究现状与展望[J].药学学报,2005(9):769-774.
[9] 李维薇, 杨燕, 汪受传,等. 细胞代谢组学研究进展[J].南京中医药大学学报,2017(2):187-192.
[10] 彭琳秀, 陈良慧, 狄留庆,等. 基于UPLC/LTQ-Orbitrap-MS技术的复方祖师麻片抗类风湿关节炎的血浆代谢组学研究[J].中草药, 2017(10):1964-1970.
[11] Qi Y, Li P, Zhang Y, et al. Urinary metabolite markers of precocious puberty[J].Mol Cell Proteomics,2012,11(1):M111.011072.
[12] Choi S, Shin J H, Lee Y R, et al. Urinary APE1/Ref-1: a potential bladder cancer biomarker[J].Dis Markers, 2016(3):7276502.
[13] Murray D M, Boylan G B, Fitzgerald A P, et al. Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden[J].Arch Dis Child-Fetal, 2008, 93(3):183-186.
[14] Dash P K, Hergenroeder G W, Jeter C B, et al. Traumatic brain injury alters methionine metabolism: implications for pathophysiology[J].Front Neurosci-Switz, 2016,(10):36.
[15] Chen Y, Dong H, Thompson D C, et al. Glutathione defense mechanism in liver injury: Insights from animal models[J].Food Chem Toxicol, 2013, 60(10):38-44.
[16] Dodd D, Spitzer M H, Treuren W V, et al. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites[J].Nature, 2017, 3(10):e00438.
[17] Uchida H, Nakajima Y, Ohtake K, et al. Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress[J].World J Gastroenterol, 2017, 23(36):6650-6664.
[18] Ananthakrishnan A N, Luo C, Yajnik V, et al. Gut microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases.[J].Cell Host Microb, 2017, 21(5):603-610.