DIET, INTESTINAL MICROFLORA AND COLORECTAL CANCER

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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.