陽虛質(zhì)糞便代謝組學(xué)特征及其與腸道菌群結(jié)構(gòu)的相關(guān)性研究
發(fā)布時(shí)間：2018-08-30 17:59
【摘要】：目的:采用基于核磁共振(NMR)的代謝組學(xué)方法,探尋陽虛體質(zhì)與平和體質(zhì)分類的客觀依據(jù)標(biāo)準(zhǔn)及微觀物質(zhì)代謝基礎(chǔ)。并通過R-3.3.2統(tǒng)計(jì)軟件,運(yùn)用因子分析(Psych)及典型相關(guān)分析(Stats)方法,將代謝組學(xué)結(jié)果與實(shí)驗(yàn)前期的菌群結(jié)構(gòu)結(jié)果進(jìn)行相關(guān)性分析。驗(yàn)證"陽虛質(zhì)腸道菌群結(jié)構(gòu)的變化影響其代謝功能,并存在與代謝相關(guān)的特征功能菌群"的推論。方法:納入符合體質(zhì)分型判定標(biāo)準(zhǔn)者共60例,按體質(zhì)類型分為:陽虛體質(zhì)組30例,平和體質(zhì)組30例。采集研究對(duì)象的糞便樣品,運(yùn)用1H-NMR技術(shù)和多元統(tǒng)計(jì)學(xué)分析方法研究不同體質(zhì)者糞便的代謝組學(xué)特征,確定其潛在生物標(biāo)記物。并尋找與陽虛質(zhì)典型代謝標(biāo)志物相關(guān)且影響宿主共代謝的特征功能菌群。結(jié)果:對(duì)比分析陽虛體質(zhì)者與平和體質(zhì)者糞便的典型代謝產(chǎn)物譜特征,以平和質(zhì)者作為比較對(duì)象,結(jié)果顯示:1.將代謝組學(xué)技術(shù)作為體質(zhì)判別的客觀理論依據(jù)是現(xiàn)實(shí)可行的。與平和質(zhì)相比,代謝通路的改變切實(shí)存在于陽虛體質(zhì)者中。2.發(fā)現(xiàn)陽虛體質(zhì)者及平和體質(zhì)者的潛在特征生物代謝標(biāo)志物,并確定其濃度的變化趨向。兩種體質(zhì)中顯著的潛在標(biāo)記物有:乳酸(Lactate,δ1.33-1.35)、丙氨酸(Alanine,δ1.46-1.50)、丙酸鹽(Propionate,81.05-1.07)、醋酸鹽(Acetate,81.90-1.93)、丁酸鹽(Butyrat e,80.88-0.92,1.56,1.57)、琥珀酸鹽(Succinate,δ2.41)、蛋氨酸(Propionate/Methionine,δ2.16-2.19)、葡萄糖(Glucose/AA,δ3-4)。其中陽虛質(zhì)組糞便中乳酸(Lactate,δ1.33-1.35)、丙氨酸(Alanine,81.46-1.50)、丙酸鹽(Propionate,δ1.05-1.07)的濃度較平和質(zhì)組高;醋酸鹽(Acetate,δ1.90-1.93)、丁酸鹽(Butyr ate,δ0.88-0.92,1.56,1.57)、琥珀酸鹽(Succinate,δ2.41)、蛋氨酸(Propiona te/Methionine,82.16-2.19)、葡萄糖(Glucose/AA,δ3-4)的濃度較平和質(zhì)組低。兩種體質(zhì)中較明顯的潛在標(biāo)記物有:纈氨酸(Ileucine/Leucine/Valine,80.95-0.97)、亮氨酸(Lysine/Leucine/Arginine,81.71-1.79)、谷氨酸鹽(Glutamate,82.05,2.06)、賴氨酸(Lysine,δ3.01-3.04)、TMA(δ2.94,2.95)、精氨酸(Arginine,δ3.25-3.27)、甘氨酸(Glycine,δ3.57)、β 葡萄糖(β-glucose,δ4.65)、α 葡萄糖(α-glucose,δ5.24,5.25)。其中陽虛質(zhì)組糞便中纈氨酸(Ileucine/Leucine/Vali ne,δ0.95-0.97)、亮氨酸(Lysine/Leucine/Arginine,δ1.71-1.79)、谷氨酸鹽(G lutamate,δ2.05,2.06)、賴氨酸(Lysine,δ3.01-3.04)的濃度較平和體質(zhì)組較高;TMA(δ2.94,2.95)、精氨酸(Arginine,δ3.25-3.27)、甘氨酸(Glycine,δ3.57)、β葡萄糖(β-glucose,δ4.65)、α葡萄糖(α-glucose,δ5.24,5.25)的濃度較平和體質(zhì)組較低。3.通過比對(duì)相關(guān)數(shù)據(jù)庫(kù)聯(lián)合查閱文獻(xiàn),闡明了具有明顯差異的代謝物的生理功能和代謝途徑。發(fā)現(xiàn)陽虛體質(zhì)者與平和體質(zhì)者在氨基酸代謝、能量代謝、糖代謝以及神經(jīng)遞質(zhì)、臟腑的生理功能變更等各生物生化方面具有其獨(dú)特的個(gè)性差異,為陽虛體質(zhì)人群的客觀化分類提供了清晰準(zhǔn)確的代謝組學(xué)支持。4.通過多變量統(tǒng)計(jì)學(xué)因子關(guān)聯(lián)分析,尋找到與陽虛質(zhì)典型代謝標(biāo)志物相關(guān)且影響宿主共代謝的特征功能菌群:陽虛質(zhì)中含量偏高的明串珠菌屬(Leuconostoc)、羅氏菌屬(Rothia)與α葡萄糖、丁酸鹽、乳酸、丙氨酸、醋酸鹽、谷氨酸鹽、蛋氨酸、琥珀酸鹽、TMA、賴氨酸、精氨酸、葡萄糖等代謝物相關(guān),陽虛質(zhì)中含量偏高的Defluviitaleaceae_incertae_sedis、Butyric imonas與α葡萄糖等代謝物相關(guān);平和質(zhì)中含量偏高的巨型球菌屬(Megasphaera)與α葡萄糖等代謝物相關(guān),平和質(zhì)中含量偏高的毛螺菌屬(Lachnospira)與葡萄糖、α葡萄糖、β葡萄糖等代謝物相關(guān),平和質(zhì)中含量偏高的瘤胃球菌屬(Ruminococcus)與葡萄糖、α葡萄糖、β葡萄糖、丁酸鹽、乳酸、丙氨酸、醋酸鹽、谷氨酸鹽、蛋氨酸、琥珀酸鹽、TMA、賴氨酸、精氨酸等代謝物相關(guān),這些啟示可用于充分挖掘?qū)号c各種復(fù)雜的影響因素之間的相關(guān)性的認(rèn)知,具有深刻現(xiàn)實(shí)意義。結(jié)論:1.陽虛體質(zhì)者與平和體質(zhì)者在氨基酸代謝、能量代謝、糖代謝以及神經(jīng)遞質(zhì)、臟腑的生理功能變更等各生物生化方面具有其獨(dú)特的個(gè)性差異,為陽虛體質(zhì)人群的客觀化分類提供了清晰準(zhǔn)確的代謝組學(xué)支持。兩種體質(zhì)的NMR代謝譜之間存在一定差異,相較于平和質(zhì),陽虛質(zhì)代謝產(chǎn)物的典型綜合特點(diǎn)為代謝標(biāo)志物的含量降低,某些標(biāo)志物出現(xiàn)應(yīng)激性回饋性略微升高。特別是能量代謝、糖代謝以及氨基酸代謝的紊亂,應(yīng)與相關(guān)臟腑的生理功能減退有關(guān)。為了理解腸道菌群與宿主代謝關(guān)系的分子基礎(chǔ),幫助促進(jìn)宿主健康與更好地診療疾病,實(shí)驗(yàn)從代謝組學(xué)分析中找出特異的標(biāo)志性代謝產(chǎn)物。2.獲得與陽虛質(zhì)典型代謝標(biāo)志物相關(guān)且影響宿主共代謝的特征功能菌群,可初步驗(yàn)證"陽虛體質(zhì)者腸道菌群結(jié)構(gòu)的改變影響其宿主的代謝功能,并存在與代謝相關(guān)聯(lián)的特征功能菌群"的推論。以明確腸道菌群中與宿主生理及健康相關(guān)的、影響宿主代謝的微觀機(jī)制,促進(jìn)了宿主健康并提供了診療保障。
[Abstract]:Objective: To explore the objective criteria and micro-material metabolic basis of classification of Yang-deficiency constitution and peaceful constitution by using nuclear magnetic resonance (NMR) based metabonomics, and to analyze the metabolomic results with the results of microbial community structure in the early stage of experiment by using R-3.3.2 statistical software, factor analysis (Psych) and canonical correlation analysis (Stats). Methods: 60 cases were included in the study. They were divided into two groups according to their constitution types: 30 cases of Yang deficiency constitution group and 30 cases of calm constitution group. NMR and multivariate statistical analysis were used to study the metabolomic characteristics of feces in different constitutions, identify potential biomarkers, and search for functional microflora associated with typical metabolic markers of Yang deficiency and affecting co-metabolism of host. Compared with the peaceful constitution, the changes of metabolic pathway actually exist in the patients with Yang-deficiency constitution. 2. The potential characteristics of metabolic markers in the patients with Yang-deficiency constitution and those with peaceful constitution were found and their concentrations were determined. Significant potential markers in both constitutions are lactic acid (Lactate, Delta 1.33-1.35), alanine (Alanine, Delta 1.46-1.50), propionate (Propionate, 81.05-1.07), acetate (Acetate, 81.90-1.93), butyrate (Butyrat, 80.88-0.92, 1.56, 1.57), succinate (Succinate, Delta 2.41), methionine (Propiate/Methionate, Delta 2.16-2.16-2.41). The concentrations of lactic acid (Lactate, Delta 1.33-1.35), alanine (Alanine, 81.46-1.50), propionate (Propion ate, Delta 1.05-1.07), acetate (Acetate, Delta 1.90-1.93), butyrate (Butyr ate, Delta 0.88-0.92, 1.56, 1.57), succinate (Succinate, Delta 2.41), methionine (Propion ate) in the feces of the Yang deficiency group were higher than those of the normal group. A te/Methionine, 82.16-2.19, and glucose (Glucose/AA, Delta 3-4) concentrations were lower than those in the plain group. The more obvious potential markers in the two constitutions were valine (Ileucine/Leucine/Valine, 80.95-0.97), leucine (Lysine/Leucine/Arginine, 81.71-1.79), glutamate (Glutamate, 82.05, 2.06), lysine (Lutamate, Delta 3.01-3.04), TMA (delta 2.94, TM 2.94). 95, arginine (Arginine, Delta 3.25-3.27), glycine (Glycine, Delta 3.57), beta glucose (beta-glucose, Delta 4.65), alpha glucose (alpha-glucose, Delta 5.24, 5.25). Among them, valine (Ileucine/Leucine/Vali ne, Delta 0.95-0.97), leucine (Lysine/Leucine/Arginine, Delta 1.71-1.79), glutamate (G-lutte, Delta 2.05, 2.06), lysine (Lysine/Leucine/Arginine, Delta 1.71-1.79), glutamate (G-lutte, Delta 2.05, 2. (Lysine, Delta 3.01-3.04) had a higher concentration than that of the calm group; TMA (delta 2.94, 2.95), arginine (Arginine, Delta 3.25-3.27), glycine (Glycine, Delta 3.57), beta glucose (beta-glucose, Delta 4.65), and alpha glucose (a-glucose, Delta 5.24, 5.25) had a lower concentration than that of the calm group.3. It was found that there were distinct individual differences in amino acid metabolism, energy metabolism, glucose metabolism, neurotransmitter, physiological function of viscera between the two groups, which provided clear and accurate metabolism for the objective classification of the people with Yang deficiency constitution. Histological support. 4. Through multivariate statistical factor correlation analysis, we found the characteristic functional microflora related to the typical metabolic markers of Yang deficiency and affecting the co-metabolism of host: Leuconostoc, Rothia and alpha glucose, butyrate, lactic acid, alanine, acetate, glutamate, methionine with high content of Yang deficiency. Defluviita leaceae_incertae_sedis and Butyric imonas with high content of Yang deficiency substance are related to metabolites such as acid, succinate, TMA, lysine, arginine and glucose; Megasphaera with high content of neutral substance is related to metabolites such as alpha-glucose, and snail with high content of neutral substance is related to Defluviita leaceae_incertae_sedis and Butyric imonas with high content of alpha-glucose. Lachnospira is associated with glucose, alpha-glucose, beta-glucose and other metabolites. Ruminococcus, which is high in the serum, is associated with glucose, alpha-glucose, beta-glucose, butyrate, lactic acid, alanine, acetate, glutamate, methionine, succinate, TMA, lysine, arginine and other metabolites. These enlightenments may include It has profound practical significance to fully tap the cognition of the correlation between the flora and various complex influencing factors. Conclusion: 1. The Yang-deficiency constitution and the peaceful constitution have their unique personality differences in amino acid metabolism, energy metabolism, glucose metabolism, neurotransmitters, physiological function changes of viscera, etc. The objective classification of Yang-deficiency constitution provides clear and accurate metabonomic support. There are some differences between the NMR metabolic profiles of the two constitutions. Compared with the placid constitution, the typical comprehensive characteristics of the metabolic products of Yang-deficiency constitution are that the content of metabolic markers decreases, and some markers show slightly increased stress feedback. In order to understand the molecular basis of the relationship between intestinal flora and host metabolism, and to help promote host health and better diagnosis and treatment of diseases, the specific metabolite markers were identified from metabolomic analysis. 2. Typical metabolic markers of Yang deficiency were obtained. The characteristic functional microflora related to the host and affecting the host's co-metabolism can preliminarily verify the inference that the alteration of intestinal flora structure in the patients with Yang deficiency constitution affects the host's metabolic function and there are characteristic functional microflora associated with metabolism. It promotes the health of the host and provides medical support.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R229
本文編號(hào)：2213848
[Abstract]:Objective: To explore the objective criteria and micro-material metabolic basis of classification of Yang-deficiency constitution and peaceful constitution by using nuclear magnetic resonance (NMR) based metabonomics, and to analyze the metabolomic results with the results of microbial community structure in the early stage of experiment by using R-3.3.2 statistical software, factor analysis (Psych) and canonical correlation analysis (Stats). Methods: 60 cases were included in the study. They were divided into two groups according to their constitution types: 30 cases of Yang deficiency constitution group and 30 cases of calm constitution group. NMR and multivariate statistical analysis were used to study the metabolomic characteristics of feces in different constitutions, identify potential biomarkers, and search for functional microflora associated with typical metabolic markers of Yang deficiency and affecting co-metabolism of host. Compared with the peaceful constitution, the changes of metabolic pathway actually exist in the patients with Yang-deficiency constitution. 2. The potential characteristics of metabolic markers in the patients with Yang-deficiency constitution and those with peaceful constitution were found and their concentrations were determined. Significant potential markers in both constitutions are lactic acid (Lactate, Delta 1.33-1.35), alanine (Alanine, Delta 1.46-1.50), propionate (Propionate, 81.05-1.07), acetate (Acetate, 81.90-1.93), butyrate (Butyrat, 80.88-0.92, 1.56, 1.57), succinate (Succinate, Delta 2.41), methionine (Propiate/Methionate, Delta 2.16-2.16-2.41). The concentrations of lactic acid (Lactate, Delta 1.33-1.35), alanine (Alanine, 81.46-1.50), propionate (Propion ate, Delta 1.05-1.07), acetate (Acetate, Delta 1.90-1.93), butyrate (Butyr ate, Delta 0.88-0.92, 1.56, 1.57), succinate (Succinate, Delta 2.41), methionine (Propion ate) in the feces of the Yang deficiency group were higher than those of the normal group. A te/Methionine, 82.16-2.19, and glucose (Glucose/AA, Delta 3-4) concentrations were lower than those in the plain group. The more obvious potential markers in the two constitutions were valine (Ileucine/Leucine/Valine, 80.95-0.97), leucine (Lysine/Leucine/Arginine, 81.71-1.79), glutamate (Glutamate, 82.05, 2.06), lysine (Lutamate, Delta 3.01-3.04), TMA (delta 2.94, TM 2.94). 95, arginine (Arginine, Delta 3.25-3.27), glycine (Glycine, Delta 3.57), beta glucose (beta-glucose, Delta 4.65), alpha glucose (alpha-glucose, Delta 5.24, 5.25). Among them, valine (Ileucine/Leucine/Vali ne, Delta 0.95-0.97), leucine (Lysine/Leucine/Arginine, Delta 1.71-1.79), glutamate (G-lutte, Delta 2.05, 2.06), lysine (Lysine/Leucine/Arginine, Delta 1.71-1.79), glutamate (G-lutte, Delta 2.05, 2. (Lysine, Delta 3.01-3.04) had a higher concentration than that of the calm group; TMA (delta 2.94, 2.95), arginine (Arginine, Delta 3.25-3.27), glycine (Glycine, Delta 3.57), beta glucose (beta-glucose, Delta 4.65), and alpha glucose (a-glucose, Delta 5.24, 5.25) had a lower concentration than that of the calm group.3. It was found that there were distinct individual differences in amino acid metabolism, energy metabolism, glucose metabolism, neurotransmitter, physiological function of viscera between the two groups, which provided clear and accurate metabolism for the objective classification of the people with Yang deficiency constitution. Histological support. 4. Through multivariate statistical factor correlation analysis, we found the characteristic functional microflora related to the typical metabolic markers of Yang deficiency and affecting the co-metabolism of host: Leuconostoc, Rothia and alpha glucose, butyrate, lactic acid, alanine, acetate, glutamate, methionine with high content of Yang deficiency. Defluviita leaceae_incertae_sedis and Butyric imonas with high content of Yang deficiency substance are related to metabolites such as acid, succinate, TMA, lysine, arginine and glucose; Megasphaera with high content of neutral substance is related to metabolites such as alpha-glucose, and snail with high content of neutral substance is related to Defluviita leaceae_incertae_sedis and Butyric imonas with high content of alpha-glucose. Lachnospira is associated with glucose, alpha-glucose, beta-glucose and other metabolites. Ruminococcus, which is high in the serum, is associated with glucose, alpha-glucose, beta-glucose, butyrate, lactic acid, alanine, acetate, glutamate, methionine, succinate, TMA, lysine, arginine and other metabolites. These enlightenments may include It has profound practical significance to fully tap the cognition of the correlation between the flora and various complex influencing factors. Conclusion: 1. The Yang-deficiency constitution and the peaceful constitution have their unique personality differences in amino acid metabolism, energy metabolism, glucose metabolism, neurotransmitters, physiological function changes of viscera, etc. The objective classification of Yang-deficiency constitution provides clear and accurate metabonomic support. There are some differences between the NMR metabolic profiles of the two constitutions. Compared with the placid constitution, the typical comprehensive characteristics of the metabolic products of Yang-deficiency constitution are that the content of metabolic markers decreases, and some markers show slightly increased stress feedback. In order to understand the molecular basis of the relationship between intestinal flora and host metabolism, and to help promote host health and better diagnosis and treatment of diseases, the specific metabolite markers were identified from metabolomic analysis. 2. Typical metabolic markers of Yang deficiency were obtained. The characteristic functional microflora related to the host and affecting the host's co-metabolism can preliminarily verify the inference that the alteration of intestinal flora structure in the patients with Yang deficiency constitution affects the host's metabolic function and there are characteristic functional microflora associated with metabolism. It promotes the health of the host and provides medical support.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R229
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