探討果寡醣、異麥芽寡醣對慣性便秘老人直結腸癌發生相關因子之調節作用

Effects of fructo-oligosaccharide and isomalto-oligosaccharide on the potential risk factors of colon cancer in constipated elders

尤宣文(Hsuan-Wen Yu)

指導教授 ： 陳曉鈴

中山醫學大學/健康管理學院/營養學研究所/碩士(2009年)

https://doi.org/10.6834/CSMU.2009.00120

摘要

一、果寡醣
目的：本實驗採飲食控制、單盲、自體比較的方法，觀察補充果寡醣後對慣性便祕老人之大腸癌發生的潛在危險因子之調節作用。
材料與方法：共計有九位受試者參與本實驗，實驗期間包含每天給予果糖水100 mL四週的控制期；接著給予四週果寡醣水(每天含10 g寡醣活性成分)；最後為四週淨空期，期間不再補充寡醣水。在每個時期的最後一週收集七天的糞便，並用來測試大腸癌發生的危險因子，包含糞便酵素活性(β-glucosidase、β-galactosidase、β-glucuronidase以及mucinase)、膽酸組成、短鏈脂肪酸濃度以及糞便水對Caco-2細胞的毒性影響。
結果：由糞便酵素得知，在補充果寡醣四週後可顯著降低β-glucosidase、β-glucuronidase以及mucinase的活性。與控制期相比，糞便膽酸濃度雖沒有顯著變化，卻可顯著改變一級/二級膽酸的組成，二級膽酸顯著下降10.4%，淨空期的二級膽酸雖有下降趨勢但未達顯著差異。補充果寡醣四週後，糞便乙酸及總短鏈脂肪酸的濃度與控制期相比有顯著增加，丙酸、正丁酸及異丁酸雖未達顯著差異但仍有增加的趨勢。與控制組相比，以糞便水處理Caco-2細胞3小時後的細胞存活率顯著上升，說明補充果寡醣四週後可顯著降低糞便水之細胞毒性；補充果寡醣四週後，可顯著降低Caco-2細胞與糞便水處理或合併使用FPG-protein誘發的DNA傷害與過氧化傷害，且此效果延續至淨空期。
結論：給予安養中心便秘老人果寡醣四週後，可顯著降低與直結腸癌相關的因子，包含降低糞便細菌酵素的活性，改變膽酸組成，增加短鏈脂肪酸濃度，並可能降低糞便物質對人類結腸表皮細胞的細胞毒性及基因毒性。

二、異麥芽寡醣
目的：本實驗採飲食控制、單盲、自體比較的方法，觀察補充異麥芽寡醣後對慣性便祕老人之大腸癌發生的潛在危險因子之調節作用。
材料與方法：共計有十二位受試者參與本實驗，實驗期間包含每天給予果糖水100mL (含3 g果糖)四週的控制期；接著給予兩次各四週的異麥芽寡醣水(含10 g寡醣活性成分)，分別為介入期1和介入期2；最後為四週淨空期，期間不再補充寡醣水。在每個時期的最後一週收集七天的糞便，並用來測試大腸癌發生的危險因子，包含糞便酵素活性(β-glucosidase、β-galactosidase、β-glucuronidase及mucinase)、膽酸組成、短鏈脂肪酸濃度及糞便水對Caco-2細胞的毒性影響。
結果：由糞便酵素得知，在補充異麥芽寡醣四週後可顯著降低β-glucuronidase及mucinase的活性，持續補充八週後仍有下降的趨勢，至淨空期mucinase仍達顯著下降。膽酸濃度雖沒有顯著變化，卻可顯著改變一級/二級膽酸的組成，補充四週後二級膽酸顯著下降10.1%，持續補充後更下降18.7%，且此效果延續至淨空期。短鏈脂肪酸的總濃度和乙酸與控制期相比有顯著增加，並持續增加至八週，至淨空期短鏈脂肪酸的總濃度雖有增加趨勢但未達顯著差異。與控制組相比，以糞便水處理Caco-2細胞3小時後的細胞存活率顯著上升，說明補充異麥芽寡醣四週及八週後可顯著降低糞便水之細胞毒性；且補充異麥芽寡醣四週後，可顯著降低Caco-2細胞與糞便水處理或合併使用FPG-protein誘發的DNA傷害與過氧化傷害，補充八週後更持續降低傷害，且此效果延續至淨空期。
結論：給予慣性便秘老人異麥芽寡醣四週及八週後，可顯著降低與直結腸癌相關的因子，包含降低糞便細菌酵素的活性，改變膽酸組成，增加短鏈脂肪酸濃度並降低細胞毒性及基因毒性，且這些效果隨著補充時間的延長更為顯著，說明異麥芽寡醣對於降低與直結腸癌相關因子的影響具有時間上的效應。

關鍵字

果寡醣 ； 異麥芽寡醣 ； 老人 ； 糞便細菌酵素 ； 膽酸 ； 短鏈脂肪酸 ； 細胞毒性 ； 基因毒性

並列摘要

A. Fructo-oligosaccharide study

Rationale & Objectives: This diet-controlled, single-blind, self-comparison study was designed to examine effects of fructo-oligosaccharides (FO) on the potential risks of colon cancer in constipated elders in nursing care unit.
Materials & Methods: Nine constipated subjects participated in this study that consisted of a 4-wk placebo period, a 4-wk FO-supplemented period (10 g active components/d), and a 4-wk post period. Stools were collected during the last week of each period to determine the potential risk factors of colon cancer. Fecal bacterial enzymes (β-glucosidase, β-galactosidase, β-glucuronidase, and mucinase) activities, the bile acid profile, short-chain fatty acid (SCFA) and fecal water cytotoxicity and genotoxicity on Caco-2 cell were determined.
Results & Findings: The activity of fecal β-glucosidase, β-glucuronidase and mucinase were significantly decreased in FO period by 59.1%, 33.7% and 36.7% respectively, as compared to that in the placebo period. The ratio of secondary bile acid to total bile acids significantly decreased by FO supplement for 10.40% as compared to that in the placebo period and the effect didn’t sustain through the post period. The concentration of total SCFA and acetate were significantly increased in FO period, as compared with placebo period. FO significantly increased cell survival when cells were treated with fecal water for 3 hrs, as compared to that with DMEM only. The tail moment, an index of the DNA damage, induced by fecal water only or fecal water combined with FPG-protein were significantly lowered by FO supplement, and these effects lasted through to the post period.
Conclusion: Supplementation of FO effectively decreased the potential risk factors of colon cancer in constipated elders, including decreased fecal bacterial enzymes, change the profile of bile acid, increased SCFA, and decreased the fecal water cytotoxicity and genotoxicity on Caco-2 cell.

B. Isomalto-oligosaccharide study

Rationale & Objectives: This diet-controlled, single-blind、self-comparison study was designed to examine effects of isomalto-oligosaccharides (IO) on the potential risks of colon cancer in constipated elders.
Materials & Methods: Twelve constipated subjects participated in this study that consisted of a 4-wk placebo period, two 4-wk IO-supplemented (IO1 and IO2) period (10 g active components/d), and a 4-wk post period. Stools were collected during the last week of each period to determine the potential risk factors of colon cancer. Fecal bacterial enzymes (β-glucosidase, β-galactosidase, β-glucuronidase, and mucinase) activities, the bile acid profile, short-chain fatty acid (SCFA) and fecal water cytotoxicity and genotoxicity on Caco-2 cell were determined.
Results & Findings: The decrease in fecal β-glucuronidase and mucinase activity by IO supplement were significant in both IO periods while β-glucuronidase and mucinase activity were decreased by nearly 40%, respectively, only in IO2 period, as compared to that in the placebo period. The ratio of secondary bile acids (lithocholic acid and deoxycholic acid) to total bile acids significantly decreased in IO1 and IO2 by 10.1% and 18.7%, respectively, as compared to that in the placebo period and the effects lasted through the post period. The concentration of total SCFA significantly increased in IO1 and IO2 by 34.8% and 63.1% while acetate was significantly increased in both IO periods, as compared with placebo. IO significantly increased cell survival when cells were treated with fecal water for 3 hrs, as compared to that with DMEM only. The tail moment, an index of the DNA damage, induced by fecal water only or fecal water combined with FPG-protein were significantly lowered by IO supplement, and these effects lasted through to the post period.
Conclusion: Supplementation of IO effectively decreased the potential risk factors of colon cancer in constipated elders, including decreased fecal bacterial enzymes, change the profile of bile acid, increased SCFA, and decreased the fecal water cytotoxicity and genotoxicity on Caco-2 cell and these results have the time effect.

並列關鍵字

fructo-oligosaccharides ； isomalto-oligosaccharides ； elders ； fecal bacterial enzyme ； bile acid ； short-chain fatty acid ； cytotoxicity ； genotoxicity

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