DIET, INTESTINAL MICROFLORA AND COLORECTAL CANCER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。中心假设：饮食定义并调节肠道菌群，饮食和肠道菌群都是结肠癌发生的可改变的危险因素。基本原理：大多数（2/3或更多）结肠癌病例似乎与非遗传、环境因素有关。然而，迄今为止，很少有研究纳入了人类大肠内容物的全面数据，尽管每克大肠约有1011个细菌，占粪便固体总量的55%。微生物生态系统是已知最复杂的生态系统之一，有数百种和亚种。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、饮食类型不同以及癌症风险不同的人群的粪便菌群模式不同。其他研究表明，粪便样本中有许多细菌菌株/形式在显微镜下可见，但不能在培养物上生长，即使用标准微生物培养基和技术无法培养。分子技术的出现为我们提供了快速、全面分析细菌群落的工具，包括可培养和不可培养的细菌。DGGE允许对肠道微生物群进行有效的分析，而16S rDNA测序允许对最普遍的肠道细菌进行半定量枚举和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。这项有60名受试者的初步研究是一项规模更大的研究的一部分，该研究将在总共500名受试者中调查这些关联。更大的研究是由美国癌症学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所提出的关联，并为更大规模的研究优化分析方法。60个主题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.