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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 沈立言 | zh_TW |
| dc.contributor.advisor | Lee-Yan Sheen | en |
| dc.contributor.author | 張健威 | zh_TW |
| dc.contributor.author | Kent-Vui Chong | en |
| dc.date.accessioned | 2021-07-11T14:58:32Z | - |
| dc.date.available | 2024-12-31 | - |
| dc.date.copyright | 2020-01-21 | - |
| dc.date.issued | 2020 | - |
| dc.date.submitted | 2002-01-01 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78466 | - |
| dc.description.abstract | 根據世界衛生組織 (World Health Organization, WHO) 的統計，心血管疾病是 2016 年造成世界人口死亡原因的榜首。而台灣衛生福利部所公佈的 107 年國人十大死亡原因中，心血管疾病所造成的死亡人數居高不下，可見相關研究被探討的必要性。近期因腸道菌相關研究的興起，腸道菌及其代謝產物如氧化三甲胺 (Trimethylamine N-oxide, TMAO) 、短鏈脂肪酸 (Short chain fatty acids, SCFAs) 及次級膽酸都被證實與心血管疾病的發生有關 。其中 TMAO 已被許多研究證實具有致粥狀動脈硬化及血栓形成的潛力。先前本實驗室在動物實驗中發現大蒜素的介入能透過調節腸道菌相，降低肉鹼飲食所造成血漿 TMAO 濃度的提高，然而相關的人體試驗卻相當缺乏。因此本次實驗想要探討於 high TMAO producers 飲食中介入新鮮大蒜汁是否能透過調節腸道菌相，來降低其血漿 TMAO 濃度及血小板過度活化的現象，進而降低心血管疾病的風險。結果顯示，在介入了一週的大蒜汁後，high TMAO producers 的血漿 TMAO 濃度有下降的趨勢，血漿 γ -丁基甜菜鹼 (gamma-butyrobetaine, ϒ-BB) 則有顯著地上升，推測大蒜汁的介入可以抑制腸道菌利用 ϒ-BB 生成 TMA 的能力。此外，大蒜汁的介入顯著降低了受試者的尿液 TMAO 濃度，且與血漿 TMAO 濃度也有顯著相關性，暗示未來可以以非侵入性的尿液檢測代替血漿 TMAO 的檢測。 High TMAO producers 的血小板凝集反應在大蒜汁介入後並無顯著差異，與預期有落差，說明人體血小板凝集反應的複雜性，靠單一因子無法造成整體的影響。菌相分析的結果顯示，high TMAO producers α-多樣性中的 Shannon index 有顯著地上升，說明大蒜汁的介入提高了受試者腸道菌相的多樣性及均勻度。主座標分析 (PCoA) 的結果顯示大蒜汁的介入對於 high TMAO producers 整體的腸道菌相組成並無造成顯著地影響，但對於特定菌相的相對豐度仍造成顯著地改變。體外試驗的結果顯示 2.5% 的大蒜汁濃度為抑制腸道菌群利用 carnitine 生成 TMA 的最低有效劑量。綜上所述，本次研究的結論為飲食中大蒜汁的介入可以透過調節腸道菌相，抑制腸道菌利用 ϒ-BB 生成 TMA 的能力，藉此減少 TMAO 的產生，進而降低心血管疾病的風險。 | zh_TW |
| dc.description.abstract | According to the estimations made by World Health Organizations (WHO) in 2016, cardiovascular diseases (CVD) were the main cause of death worldwide. Taiwan Ministry of Health and Welfare also stated that CVD remained one of the greatest cause of death in Taiwan population. Recently, gut microbiota related metabolites, trimethylamine N-oxide (TMAO) has gain more attentions with its proatherogenic and prothrombic potentials. Many studies have showed that elevated plasma TMAO increased the risk of major adverse cardiovascular events (MACE). Recently, our laboratory works showed that synthesized allicin, a major bioactive compound in garlic can prevent the elevation of plasma TMAO caused by carnitine diet in animal studies. However, the effects of garlic on the production of TMAO in human studies were yet to prove. Therefore, the aim of this study is to investigate whether fresh garlic juice can decrease the elevation of plasma TMAO in high TMAO producers after consuming carnitine supplements and lower the platelet aggregation through modulation of gut microbiota. The results showed that garlic juice intervention reduced plasma TMAO and significantly increased plasma gamma-butyrobetaine (ϒ-BB) in high TMAO producers indicating the transformation of ϒ-BB into TMA in our gut microbiota was inhibited. Urine TMAO exhibited a strong correlation with plasma TMAO. Hence, urine can be an alternative non-invasive test for TMAO measurement. Platelet aggregation of high TMAO producers showed no significant differences after garlic juice intervention suggested that there are many other factors like thromboxane A2 and serotonin affecting platelet aggregation in human. Gut microbiota analysis of high TMAO producers showed that the Shannon index increased significantly after garlic juice intervention. Principal coordinate analysis (PCoA) showed no significant differences of overall gut microbiota composition after garlic juice intervention in high TMAO producers. However, the relative abundances of specific gut microbiota like Akkermansia, Lachnospiraceae and Christensenellaceae in genus level showed significant differences after garlic juice intervention. In vitro study showed that 2.5% of garlic juice concentration would inhibit the growth of bacteria and thus prevent the formation of TMA. In conclusion, fresh garlic juice reduced production of TMAO by preventing the transformation of ϒ-BB to TMA through modulation of gut microbiota indicating garlic as a potential food therapy to decrease CVD risk. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:58:32Z (GMT). No. of bitstreams: 1 ntu-109-R06641040-1.pdf: 4997309 bytes, checksum: a29660788476957100e0336303a1cf9c (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 中文摘要 I
Abstract II 目錄 III 圖次 VI 表次 IX 縮寫表 X 第一章 前言 1 第二章 文獻回顧 3 第一節 心血管疾病 3 一、心血管疾病之流行病學 3 二、心血管疾病之危險因子 3 三、紅肉與心血管疾病 4 第二節 腸道菌相 5 一、人體腸道菌相的形成 5 二、人體腸道菌的功用 6 第三節 氧化三甲胺 9 一、氧化三甲胺 (Trimethylamine, TMAO) 的生成 9 二、氧化三甲胺具提高心血管疾病風險的潛力 9 第四節 大蒜素 13 一、大蒜 13 二、大蒜素 (Allicin) 抗微生物之作用及其對於腸道菌相的影響 14 第三章 研究假說與目的 16 一、研究背景 16 二、研究假說 17 三、研究目的 17 第四章 實驗架構 18 一、大蒜汁製備及 allicin 含量之鑑定 18 二、人體試驗之設計 19 三、體外試驗設計 20 第五章 實驗材料與方法 22 第一節 實驗材料 22 一、大蒜 22 二、實驗藥品 22 三、實驗設備及器材 24 第二節 實驗方法 25 一、大蒜汁製備 25 二、大蒜汁中大蒜素 (Allicin) 的含量鑑定 25 三、人體試驗之設計 26 四、血液及尿液樣本生化數值之檢測 27 五、液相層析串聯質譜儀 (liquid chromatography-tandem mass spectrometry, LC-MS/MS) 27 血液樣本 27 六、血小板凝集試驗 (Platelet aggregation test) 28 七、菌相分析 28 八、體外試驗 (In vitro study) 之設計 29 第三節 統計分析 31 第六章 實驗結果 32 一、大蒜汁中大蒜素 (allicin) 含量的檢定 32 二、High TMAO producers 之篩選 32 三、大蒜汁介入後對於血液生化數值的影響 33 四、大蒜汁對於 High TMAO producers 血漿 TMAO 的影響 34 五、大蒜汁對於 high TMAO producers 血漿 carnitine 及 ϒ-BB 的影響 34 六、大蒜汁對於 high TMAO producers 血小板凝集反應的影響 35 七、大蒜汁對於 high TMAO producers 尿液 TMAO、 carnitine 及 ϒ-BB 的影響 35 八、腸道菌相分析 36 第一節 菌相多樣性分析 (Diversity analysis) 36 第二節 菌相相對豐度分析 (Relative abundance) 36 九、體外試驗 (In vitro study) 37 第一節 大蒜汁對於菌種將 ϒ-BB 轉換至 TMA 的能力之影響 37 第二節 大蒜汁對於菌群將 carnitine 轉換至 ϒ-BB 的能力之影響 37 第二節 大蒜汁對於 high TMAO producers 糞便菌群產 TMA 能力的影響 38 第七章 實驗討論 40 一、大蒜汁劑量設計及其大蒜素的穩定性 40 二、High TMAO producers 的篩選依據 40 三、大蒜汁對於人體血清生化指標的影響 41 四、大蒜汁對於 high TMAO producers 血漿 TMAO、 carnitine 及 ϒ-BB 的影響 41 五、大蒜汁對於 high TMAO producers 血小板凝集反應的影響 42 六、大蒜汁對於 high TMAO producers 尿液 TMAO、 carnitine 及 ϒ-BB 的影響 43 七、大蒜汁對於 high TMAO producers 腸道菌相的影響 44 第一節 腸道菌相多樣性 (Gut Microbiota Diversity) 44 第二節 腸道菌相組成 (Gut Microbiota Composition) 45 八、大蒜汁對於菌群產 TMA 能力的影響 46 第八章 實驗結論 48 第九章 未來研究方向 50 第十章 實驗結果圖表 51 第十一章 參考文獻 82 第十二章 附錄 91 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 探討大蒜汁對於人體腸道菌相與氧化三甲胺 (TMAO) 生成的影響 | zh_TW |
| dc.title | Investigation on chemopreventive effects of garlic juice on human gut microbiota and TMAO production | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 108-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 朱永麟;莊曉莉 | zh_TW |
| dc.contributor.oralexamcommittee | Yung-Lin Chu;Hsiao-Li Chuang | en |
| dc.subject.keyword | 心血管疾病,氧化三甲胺,肉鹼,腸道菌,大蒜素,血小板凝集, | zh_TW |
| dc.subject.keyword | CVD,gut microbiota,TMAO,allicin,?-BB,platelet aggregation, | en |
| dc.relation.page | 109 | - |
| dc.identifier.doi | 10.6342/NTU202000091 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2020-01-16 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 食品科技研究所 | - |
| dc.date.embargo-lift | 2024-12-31 | - |
| 顯示於系所單位： | 食品科技研究所 | |
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