EFFECT OF FAT AND FIBER ON COLONIC INTESTINAL EPITHELIAL CELLS

脂肪和纤维对结肠肠上皮细胞的影响

• 批准号: 6246952
• 负责人: STEVEN J SHIFF
• 金额: $ 5.86万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-27 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6246952
• 关键词: biopsy; blood chemistry; butyrates; clinical research; colon neoplasms; dietary fiber; dietary lipid; endoscopy; feces analysis; gastrointestinal epithelium; gene mutation; human subject; nutrition related neoplasm /cancer; nutrition related tag; oncogenes

Colon cancer is a common human malignancy. Dietary fat and fiber have been shown to affect the incidence of colorectal cancer. Populations consuming diets high in fat and low in fiber overall have greater incidence rates of colorectal cancer, compared to populations consuming less fat and more fiber. It is not entirely clear whether dietary fat and fiber are independent variables with respect to colon carcinogenesis. Sodium butyrate, a short chain fatty acid, is generated in the colon in large quantities as dietary fiber is fermented by colonic bacteria. Sodium butyrate, in vitro, reduces the proliferation and induces apoptosis in cultured colon cancer cells. This research examines the effect of different levels of dietary fat and fiber on the proliferation and death of colonic epithelial cells. Subjects are given a well-controlled diet (weight maintaining, metabolic), with fat/fiber combination (high, normal or low fat and high, normal or low fiber) as the independent variable. Upon admission, after baseline endoscopic biopsy (by flexible sigmoidoscopy), subjects are placed on a low fat, high fiber diet for 4 wks. Assessment of colonic epithelium, sodium butyrate, and Ki-ras oncogene mutations are performed using endoscopic biopsy, blood, and stool samples. During the funding period 12/01/95 - 11/30/96 a total of 2 subjects have completed the study. Both subjects received a high fiber/low fat diet for 30 days (21.5% fat P/S ratio 1.5, 15.4% protein, 63.2% CHO, 47 g dietary fiber/2400Cal). Both subjects tolerated the study and the procedures involved without event. All subjects have had multiple colonic biopsies taken without difficulty or side effects. There are no definitive scientific results to report at this time. However, several important general conclusions can be made from these studies. First, multiple weekly flexible sigmoidoscopy examinations can be done safely in human volunteers with minimal, if any, adverse effects over 4 weeks. There are no major effects on the microscopic structure of the colonic mucosa after multiple repeated mucosal biopsies. There is early indication based on purely qualitative data on 2 subjects that high fiber in the diet affects the extent of apoptosis in the colon mucosa.

结肠癌是人类常见的恶性肿瘤。饮食中的脂肪和纤维 已被证明会影响结直肠癌的发病率。人口 食用高脂肪和低纤维的饮食总体上有更大的 与消费人群相比，结直肠癌的发病率 脂肪较少，纤维较多。目前还不完全清楚饮食中的脂肪和 纤维是结肠癌发生的独立变量。 丁酸钠是一种短链脂肪酸，在结肠中产生。 大量的膳食纤维是由结肠菌发酵的。 丁酸钠在体外可抑制细胞增殖并诱导细胞凋亡 在培养的结肠癌细胞中。这项研究考察了 不同水平的膳食脂肪和纤维对细胞增殖和死亡的影响 结肠上皮细胞。受试者的饮食控制得很好 (保持体重，代谢)，脂肪/纤维组合(高，正常 或低脂肪和高、正常或低纤维)作为自变量。 入院时，基线内窥镜活检后(通过灵活的 乙状结肠镜检查)，受试者被安排低脂肪、高纤维饮食，共4次 每周。结肠上皮、丁酸钠和Ki-ras的评价 癌基因突变是使用内窥镜活检、血液和粪便进行的。 样本。 在资助期12/01/95-11/30/96期间，共有2个科目 完成了研究。两名受试者都接受了高纤维/低脂肪饮食 30日龄(脂肪21.5%，P/S比1.5，蛋白质15.4%，CHO 63.2%，日粮47g 光纤/2400Cal)。两名受试者都接受了这项研究和程序 在没有事件的情况下参与。所有受试者都做了多次结肠活检 服用时没有困难或副作用。目前还没有确定的 在这个时候报告科学结果。然而，几个重要的 从这些研究中可以得出一般性的结论。第一，多个 每周可弯曲乙状结肠镜检查在人体内是安全的 志愿者在4周内不良反应最小，如果有的话。确实有 术后对结肠粘膜的显微结构无明显影响 多次重复的粘膜活检。有早期迹象表明， 关于饮食中高纤维影响的两个受试者的纯定性数据 结肠粘膜中细胞凋亡的程度。