Colonic Bacterial Synthesis of Butyric Acid

描述(申请人提供)：大肠细菌发酵 碳水化合物会导致丁酸(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 对菌落粘膜有毒性。关于BA是如何生产的，人们知之甚少 受碳水化合物发酵的影响，尤其是在 婴儿。目前对BA的结肠合成的理解是基于 底物与结肠液的孵育或对肠腔的测量 浓度，这两者都不能反映实际的合成。基于 使用稳定同位素技术的初步数据，调查人员 假设BA供应到婴儿的结肠可以通过 双糖发酵这种婴儿的饲料中存在的双糖的发酵 低聚果糖，如菊糖，会有益地增加 结肠中的双歧杆菌(益生菌效应)，但目前尚不清楚是否喂食 菊粉能促进BA的形成。初步数据表明，菊粉饲喂 可能会缓解严重的二糖吸收不良的一些不良影响 关于结肠的结构和功能。据推测，温和的 二糖吸收不良刺激盲肠和肠腔内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)和菊糖 会减弱这一效果。为了长期评估这些总体假设， 将研究18-19日龄导尿仔猪的结肠BA合成 将进行量化，以解决三个具体目标：目标1.确定 二糖吸收不良(0-5g/小时)和菊粉饲喂对BA的影响 对盲肠和左半结肠远端肠腔内BA浓度的影响。 目的2.确定二糖吸收不良或菊粉喂养是否导致 结肠炎症或损伤或影响细胞动力学(隐窝细胞 增殖率和细胞凋亡率)和促凋亡基因Bax的表达 蛋白。目的3.确定盲肠内注入BA对结肠的影响 结构和细胞动力学。使用Aim I关于高利率和正常利率的数据 BA生产，将评估高BA灌注率的效果，在 正常仔猪的两个时间点及BA供应正常化的影响 严重二糖期仔猪低BA输注率的研究 吸收不良也将被研究。

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.