Colonic Bacterial Synthesis of Butyric Acid

描述（由申请方提供）： 碳水化合物将导致丁酸（BA）的结肠腔合成。 向结肠细胞持续供应BA对于促进正常的 细胞增殖和凋亡的平衡，但过多的BA可能 对结肠粘膜有毒。关于BA的生产如何 在结肠腔中的碳水化合物的发酵，特别是在 婴儿。目前对BA的结肠合成的理解是基于以下两种情况： 底物与结肠液的孵育或对管腔的测量 浓度，两者都不能反映实际合成。基于 研究人员利用稳定同位素技术获得了初步数据， 假设可以通过以下方式维持对婴儿结肠的BA供应 这些婴儿的食物中存在的双糖的发酵。 低聚果糖如菊糖可有益地增加 肠道中的益生菌（益生元效应），但尚不清楚是否喂养 菊粉促进BA的形成。初步数据表明， 可以改善严重的二糖吸收不良的一些副作用 结肠的结构和功能据推测， 二糖吸收不良刺激盲肠中的管腔BA合成， 盲肠细胞增殖，但也假设严重的二糖 吸收不良抑制BA合成（和细胞增殖）， 减弱这种影响。为了评估这些总体假设， 将对18-19日龄的插管仔猪进行研究， 将被量化，以实现三个具体目标：目标1。以确定 二糖吸收不良（0- 5g/hr）或菊粉饲喂对BA的影响 产生和盲肠和远端左结肠腔浓度的BA。 目标二。为了确定是否二糖吸收不良或菊粉喂养导致 结肠炎症或损伤或影响细胞动力学（隐窝细胞 增殖率和凋亡）和Bax，一种促凋亡蛋白的表达。 蛋白目标3：为了确定盲肠灌注BA对结肠的影响， 结构和细胞动力学。利用目标一的数据， BA生产，将评估高速率BA输注的效果， 两个时间点，在正常仔猪和正常BA供应的影响 在严重双糖血症期间， 还将研究吸收不良。

DESCRIPTION (provided by applicant): Colonic bacterial fermentation of carbohydrate will result in the colonic luminal synthesis of butyric acid (BA). A consistent supply of BA to the colonocyte is necessary to promote a normal balance of cell proliferation and apoptosis in this organ, but excessive BA may be toxic to the colonie mucosa. Little is known about how the production of BA in the colonic lumen is affected by fermentation of carbohydrate, especially in infants. Current understanding about colonic synthesis of BA is based either on incubations of substrates with colonic fluid or on measurements of luminal concentrations, neither of which may reflect actual synthesis. Based on preliminary data using a stable isotope technique, the investigators hypothesize that BA supply to the colon of the infant can be maintained by fermentation of disaccharides present in the feedings of such infants. Fructooligosaccharides such as inulin cause a beneficial increase in bifidobacteria in the colon (prebiotic effect), but it is not clear if feeding inulin enhances BA formation. The preliminary data suggest that inulin feeding may ameliorate some of the adverse effects of severe disaccharide malabsorption on colonic structure and function. it is hypothesized that moderate disaccharide malabsorption stimulates luminal BA synthesis in the cecum and cecal cell proliferation, but it is also hypothesized that severe disaccharide malabsorption depresses BA synthesis (and cell proliferation) and that inulin attenuates this effect. To assess these overall hypotheses, chronically catheterized piglets, aged 18-19 d, will be studied and colonic BA synthesis will be quantified in order to address three Specific Aims: Aim 1. To determine the effects of disaccharide malabsorption (0-5 g/hr) or inulin feeding on BA production and on cecal and distal left colonic luminal concentrations of BA. Aim 2. To determine whether disaccharide malabsorption or inulin feeding cause colonic inflammation or injury or affect cell kinetics (crypt cell proliferation rate and apoptosis) and the expression of Bax, a pro-apoptotic protein. Aim 3. To determine the effect of cecal infusion of BA on colonic structure and cell kinetics. Using data from Aim I on high and normal rates of BA production, the effects of a high rate of BA infusion will be evaluated, at two time points, in normal piglets and the effects of normalizing BA supply with a low rate of BA infusion in piglets during severe disaccharide malabsorption also will be studied.