臺灣博碩士論文加值系統

慢性便秘為國人常見的慢性腸道疾病之一，在美國成年人中，報告發生率範圍從3-30％，平均約15％。便秘的婦女發生率是男生的兩倍，便秘更是中老年人常見的疾病。文獻報告指出發酵乳（Ferment milk）可調節腸道蠕動時間，降低因為長時間蠕動而引起某些大腸疾病的敏感性，而人體腸道內菌叢可藉由飲食型態的改變，使有益菌及有害菌數量改變，達到改善人體腸道菌叢的目的，本研究為市售的統一原味多多活菌發酵乳對慢性便秘女性之改善胃腸蠕動，減少便秘之臨床評估，以及對改善胃腸蠕動，減少便秘之動物試驗希望藉此達到方便有效又安全的治療效果，並評估臨床生理機轉。
此計畫之人體試驗乃規畫收集30位受試者，採用單盲試驗，實驗共分成穩定期、安慰劑期、實驗期及排空期。穩定期為10天，在於調整受試者之飲食習慣，以及觀察受試者之配合度等，配合度不佳者於此期即予以排除；安慰劑期10天，為飲用不含乳酸菌之多多安慰劑；實驗期則飲用20天含乳酸菌之多多活菌發酵乳（原味）200ml；排空期為受試者停喝10天之問卷及糞便分析。
此研究目的為評估統一多多活菌發酵乳（原味）產品是否具有改善便祕、促進排便之效果。此外，也進行糞便的菌相分析，以評估試驗產品是否有改善腸道菌相之作用。同時，也評估糞便中TGF-beta, IL-10, IL-6, IFN-gamma之細胞免疫激素濃度。
動物試驗部份的實驗內容主要參考行政院衛生署公布的「健康食品之胃腸功能改善評估方法」進行試驗，試驗分為離體及體內實驗二部分進行。
第一部分為消化器官之組織收縮試驗，此為離體實驗，將SD大鼠的胃、小腸、結腸組織取出後，加入不同劑量之測試樣品，測試樣品包括：安慰劑、一倍（1X）多多活菌發酵乳（正常劑量）及三倍（3X）多多活菌發酵乳（高劑量），樣品加入後監控各組織的收縮情況並計算組織張力。
第二部分為體內實驗，將ICR小鼠隨機分成四組，每組12隻小鼠，分別為生理食鹽水組、安慰劑組、一倍（1X）多多活菌發酵乳（正常劑量組）及三倍（3X）多多活菌發酵乳（高劑量組）。各組小鼠皆進行餵食各樣品四週，餵食期間定時收集且觀察各組小鼠糞便之粒數、濕重、乾重及形狀，並記錄之。接著於隔日再管灌餵食以上四組樣品，且樣品中皆加入微量的紅色色素，經一段時間後立刻斷頭將小鼠犧牲，取出胃及腸道器官，以測量組織長度及色素前進距離，再依公式計算胃腸排空率。
根據本實驗結果證實，統一多多活菌發酵乳（原味）每日200ml確實可改善年輕女性便秘患者之排便情況，且可增加排便頻率、雙叉桿菌和乳酸桿菌群之數量（p < 0.05）。因此整體而言，此統一多多活菌發酵乳（原味）產品具有相當良好之促進排便作用，且對雙叉桿菌及乳酸桿菌的菌群有顯著提升的效果存在，但並無法有效地降低壞菌的數量。在不同實驗期間之細胞激素雖有變化，但因個體間之差異變化極大，因此統計分析結果皆無顯著差異存在。
動物試驗部份實驗結果顯示，第一部份之離體試驗，SD大鼠的胃、小腸、結腸肌肉組織在加入劑量大於120 μl/ml劑量一倍的多多發酵乳樣品後，即開始出現微弱的組織收縮現象，並隨著添加多多樣品的劑量增加而增強收縮，因此有劑量依賴性，而添加三倍多多樣品的組織，其刺激效果大於一倍劑量的多多。在小鼠的體內實驗中，餵食一倍及三倍多多發酵乳二週之後，小鼠之糞便粒數及水份含量皆較餵食生理食鹽水或安慰劑組之小鼠有顯著性增加的現象（p < 0.05）。在胃腸排空率試驗中，也證實餵食一倍及三倍多多發酵乳小鼠的胃腸道，其色素移動距離皆較生理食鹽水或安慰劑組遠，即餵食多多後小鼠之胃腸排空率在統計上有顯著性提高的現象（p < 0.05）。
綜合以上人體實驗及離體實驗及體內試驗結果，本研究證實統一多多活菌發酵乳確實具有促進腸道蠕動及改善年輕女性便秘患者之排便情況的效果。

?? The research is the subsidiary plan that the Uni-President Enterprises consign “Uni-President Yakult series: Original Yakult, Milk Yakult, Uni-President Yakult probiotic drink(original)and AB fermented powders improve and evaluate the bowel’s function along with the test for the fungus safety.
?? The Second one evaluate clinically that: Uni-President Yakult probiotic drink (original) ameliorate the slight constipated women’s enterogastric peristalsis to reduce the Constipation disease.
?? The human experimentation of the subsidiary plan arrange thirty experimenter and adopt the single-blinded experiment. They are divided into the stable phase, placebo phase, experiment phase and removal phase. The stable phase maintains ten days. It regulates the experimenters’ eating habit and observes the cooperation degree of these ones. It will exclude the low cooperated degree ones from the phase experiment. The stable phase maintains ten days and they drink the Yakult placebo without the actobacillus. The experiment phase is that the experimenters drink 200ml Yakult probiotic drink (original) with the actobacillus for twenty days. The removal phase is that the experimenters stop to drink for ten days and do the questionnaires and the analysis of the excrement.
?? The purpose is to evaluate whether the Uni-President Yakult probiotic drink(original) has the effect of improving Constipation and enhance defecation. Besides, it does the analysis of the excrement’s microflora to evaluate whether the testing products enhances the bowel’s microflora. Meanwhile, it also evaluates the dense of cells’ Immune hormone for the TGF-beta, IL-10, IL-6, IFN-gamma of the excrement.
?? According to the experiment result proved that Uni-President Yakult probiotic drink (original) with daily -200ml really can ameliorate the constipated young women’s evacuation condition. Further it can also increase the frequency of evacuation, the quantity in the bifid bacterium and the lactobacillus ensemble (p<0.05). As a result for the general condition, the Uni-President Yakult probiotic drink (original) does benefits with the evacuation condition and has the effect of promoting the bifid bacterium and the lactobacillus ensemble. However, it cannot reduce effectively the magnitude of the pernicious.

中文摘要………………………………………………………………………… 1
第一章 前言…………………………………………………………………… 4
第二章 文獻探討……………………………………………………………… 5
2.1益生菌和中醫觀點………………………………………………….......... 5
2.2便祕診斷標準…………………………………………………………….. 5
2.3益生菌對腸胃道近期相關的研究成果………………………………….. 7
2.4益生菌相關生理現象的影響…………………………………………….. 7
2.5益生菌對疾病研究的應用……………………………………………….. 8
第三章 實驗方法……………………………………………………………… 10
3.1實驗內容及實驗樣品之基本資料……………………………………….. 10
3.2實驗設計………………………………………………………………….. 10
3.3試驗之主要納入與排除條件…………………………………………….. 11
3.4試驗執行流程…………………………………………………………….. 12
3.5統計方法………………………………………………………………….. 17
第四章 結果…………………………………………………………………… 19
4.1受試者基本資料分析…………………………………………………….. 19
4.2受試者身體質量指數(BMI)變化………………………………………… 19
4.3受試者便祕指數變化及排便頻率……………………………………….. 20
4.4受試者腸道菌叢變化…………………………………………………….. 21
4.5糞便細胞免疫激素分析………………………………………………….. 27
4.6大鼠消化器官之組織收縮試驗………………………………………….. 27
4.7小鼠排便試驗…………………………………………………………….. 30
4.8小鼠之胃腸排空率試驗………………………………………………….. 31
第五章 討論…………………………………………………………………… 33
第六章 結論…………………………………………………………………… 37
參考資料………………………………………………………………………… 38
附錄1、統計分析………………………………………………………………. 40
附錄2、中國醫藥大學附設醫院施行人體試驗計畫同意書…………………. 44
附錄3 、ROMO III and IBS-C criteria…………………………………………. 45
附錄4、問卷……………………………………………………………………. 46
英文摘要………………………………………………………………………… 52
感謝辭…………………………………………………………………………… 54


圖 目 錄

圖3.1…………………………………………………………………………….. 12
圖4.1…………………………………………………………………………….. 20
圖4.2…………………………………………………………………………….. 22
圖4.3…………………………………………………………………………….. 23
圖4.4…………………………………………………………………………….. 24
圖4.5…………………………………………………………………………….. 25
圖4.6…………………………………………………………………………….. 25
圖4.7…………………………………………………………………………….. 26
圖4.8…………………………………………………………………………….. 28
圖4.9…………………………………………………………………………….. 29
圖4.10……………………………………………………………………….. 29-30
圖4.11…………………………………………………………………………… 31
圖4.12…………………………………………………………………………… 32





















表 目 錄

表3.1…………………………………………………………………………….. 13
表4.1……………………………………………………………………………. 19
表4.2……………………………………………………………………………. 20
表4.3……………………………………………………………………………. 27

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中文：
15. 陳建甫、徐美菁、謝昌成、吳克恭：益生菌的臨床應用現況。基層醫學1996;22(8):290-293.
16. 吳國豪：糙米發酵飲品之製造與抗氧化性質研究。中興大學食品暨應用生物科技學系碩士論文2007.