DIET, INTESTINAL MICROFLORA AND COLORECTAL CANCER

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。中心假设：饮食定义和调节肠道微生物区系，饮食和肠道微生物区系都是结肠癌发生的可改变的危险因素。理论基础：大多数(2/3或更多)的结肠癌病例似乎与非遗传的环境因素有关。然而，到目前为止，很少有研究纳入关于人类大肠内容物的全面数据，尽管每克约有1011个细菌，占总粪便固体的55%。微生物生态系统是已知的最复杂的生态系统之一，有数百个物种和亚种。使用传统微生物学技术进行的研究表明，来自不同地理区域的人群的粪便菌群模式不同，他们食用不同类型的饮食，并具有不同的癌症风险。其他研究表明，粪便样本中有一些细菌菌株/形式在显微镜下可以看到，但不能在培养物上生长，也就是说，它们不能使用标准的微生物培养基和技术进行培养。分子技术的出现为我们提供了快速、全面地分析细菌群落的工具，包括可培养和不可培养的细菌。DGGE可以有效地分析肠道微生物区系，而16S rDNA测序既可以对最常见的肠道细菌进行半定量计数，也可以检测迄今未知的肠道微生物。有了这些工具，我们第一次能够寻找饮食、肠道菌群和结肠癌之间的联系。这项拟议的60名受试者的初步研究是一项更大规模研究的一部分，该研究将在总共500名受试者中调查这些关联。这项更大规模的研究是由美国癌症协会指导的研究学者资助的。试点研究将使我们能够更深入地调查拟议的关联，并优化更大规模研究的分析方法。60名受试者试点研究的结果也将成为重新向NCI提交雄心勃勃的PPG的基础，从而有望获得额外的外部资金。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Central hypothesis: Diet defines and modulates the intestinal microflora, with both diet and intestinal microflora serving as modifiable risk factors for the occurrence of colon cancer. rationale: The majority (2/3 or more) of colon cancer cases appear to be associated with non-hereditary, environmental factors. However, few studies to date have incorporated comprehensive data on the contents of the human large bowel, despite the approximately 1011 bacteria per gram that constitute 55% of total stool solids. The microbial ecosystem is one of the most complex known, with several hundred species and subspecies. Studies conducted using traditional microbiologic techniques have suggested that patterns of fecal flora differ among groups from different geographic areas, who are consuming different types of diets, and who have different cancer risks. Additional studies suggest that there are a number of bacterial strains/forms in stool samples that are visible by microscopy but that do not grow on cultures i.e., they non-culturable using standard microbiologic media and techniques. The advent of molecular technology has provided us with tools that permit rapid, comprehensive analysis of bacterial communities including both the culturable and +non-culturable+ bacteria. Whereas DGGE allows for an efficient profiling of the intestinal microflora, 16S rDNA sequencing allows for both the semiquantitative enumeration of the most prevalent gut bacteria and the detection of hitherto unknown gut microbes. With such tools, we are in a position, for the first time, to look for linkages among diet, intestinal flora, and colon cancer. The proposed pilot study with 60 subjects is part of a larger study that will investigate these associations in a total of 500 subjects. The larger study is funded by an ACS mentored research scholar grant to the PI. The pilot study will allow us to investigate the proposed associations in more depth and optimize the analysis approach for the larger study. The results from the 60 subject pilot study will also form the basis for the resubmission of an ambitious PPG to the NCI and thus hopefully lead to additional extramural funding.