Mäkivuokko Harri, Nurmi Jussi, Nurminen Päivi, Stowell Julian, Rautonen Nina
Danisco Innovation, Enteromix Research, Kantvik, Finland.
Nutr Cancer. 2005;52(1):94-104. doi: 10.1207/s15327914nc5201_12.
A 4-stage colon simulator and a cell culture-based human intestinal epithelial function model were combined to study the effects of a soluble fiber, polydextrose (PDX), on intestinal microbes and mucosal functions relevant to the risk of colon cancer. We observed sustained degradation of PDX throughout the different stages of the model. The fermentation was characterized by gradual degradation of PDX, production of short-chain fatty acids, and no increasing in putrefactive markers. We observed less marked effects in the microbial densities. When we applied colon fermentation metabolites obtained from the simulators with PDX to Caco-2 colon cancer cell line, a significant dose-dependent decreasing effect on cyclooxygenase-2 (COX-2) and an increasing effect on COX-3 expression levels were observed. PDX concentration appeared not to have effect on the expression levels of COX-1. Overexpression of COX-2 and decreased expression of COX-1 have been suggested to be characteristics of colon cancer. The exact physiological role of COX-3, an intron-retaining splice variant of COX-1, is not known, but it is suspected to play a role in transcriptional regulation of COX-1 and COX-2. In vitro modulation of COX expression by colon microbial fermentation products of polydextrose offers an interesting starting point for further studies on possible risk-decreasing effect of PDX on the development of colon cancer.
将一个4阶段结肠模拟器和一个基于细胞培养的人类肠上皮功能模型相结合,以研究一种可溶性纤维——聚葡萄糖(PDX)对与结肠癌风险相关的肠道微生物和黏膜功能的影响。我们观察到在模型的不同阶段,PDX持续降解。发酵的特征是PDX逐渐降解、产生短链脂肪酸,且腐败标志物没有增加。我们观察到微生物密度的变化不太明显。当我们将从含PDX的模拟器中获得的结肠发酵代谢产物应用于Caco-2结肠癌细胞系时,观察到对环氧合酶-2(COX-2)有显著的剂量依赖性降低作用,对COX-3表达水平有增加作用。PDX浓度似乎对COX-1的表达水平没有影响。COX-2的过表达和COX-1的表达降低被认为是结肠癌的特征。COX-3是COX-1的一种保留内含子的剪接变体,其确切的生理作用尚不清楚,但怀疑它在COX-1和COX-2的转录调控中起作用。聚葡萄糖的结肠微生物发酵产物对COX表达的体外调节为进一步研究PDX对结肠癌发生可能的风险降低作用提供了一个有趣的起点。