Abstract 234: Association between fecal microbiome, diet, and colon adenomas and hyperplastic polyps
Authors: Yu Yang , Millstein Joshua , Hwang Amie E. , Ma Bing , Yu Guoqin , Buchanan Laura H. , Humphreys Michael , Hamilton Ann S. , Zadnick John , Cockburn Myles G. , Buxbaum James , Lenz Heinz-Josef , Mack Thomas M. , Ravel Jacques , Cozen Wendy 
Published: July 2017

Abstract
Background: Colorectal cancer arises from adenomatous and serrated colon polyps that are identifiable with colonoscopy. Generally, a healthy gut is characterized by higher fecal microbiota. We conducted a study to determine whether fecal microbiota composition and structure are associated with colon adenomas and hyperplastic polyps in a set of identical (MZ, monozygotic) twins.
Methods: We enrolled 83 individual twins from the California Twin Program. Of these, 56 (representing 38 twin pairs) had documented past colonoscopy and no gastrointestinal diseases, cancer or recent antibiotic use. Body mass index (BMI) and food frequency information was collected 15 years before stool collection and again at the time of stool collection. The V4 region of the 16S rRNA gene was sequenced using the HiSeq 2500 system. Alpha diversity measures including number of OTU (operational taxonomic units) and Shannon index were calculated for each sample. Mixed ANOVA models with a random effect accounting for twin pair status, were used to examine the association of alpha diversity with polyp status.
Results: Alpha diversity measured by Shannon index and number of unique OTUs was inversely associated with obesity and high beef consumption and positively associated with yogurt consumption. Surprisingly, we found that fecal microbiota alpha diversity was higher in subjects with adenomas and hyperplastic polyps compared to subjects with no polyps. When restricted to subjects with colonoscopy in the 3 years prior to stool collection, differences were stronger and statistically significant (mean OTUs for subjects with adenoma, hyperplastic polyps and no polyps = 908, 850, and 801, respectively; Padenoma vs. no = 0.017, Phyperplastic vs no = 0.007; Plinear trend= 0.018). In order to determine whether diet changes may have played a role, we examined dietary change from food frequency questionnaires collected 15 years apart. We found that subjects with no polyps increased yogurt consumption by 50% over the 15 year period, whereas subjects diagnosed with adenomas and hyperplastic polyps increased their yogurt consumption more (140% and 130%, respectively).
Conclusion: Participants diagnosed with adenomas and hyperplastic polyps had higher fecal microbiota alpha diversity compared to those without polyps. The timing of measurement of fecal microbiota years after colonoscopy obscures the causal relationship between adenoma and fecal microbiome. One possibility is that subjects may have increased their yogurt consumption after a polyp diagnosis, resulting in increased fecal alpha diversity, compared to subjects who were not diagnosed with polyps. Alternatively, polyp removal may alter microbial diversity. A third possibility is that polyp susceptibility is associated with an outgrowth of deleterious bacteria, still present after polyp removal, reflected as increased alpha diversity. Twin comparisons will be presented.
Citation Format: Yang Yu, Joshua Millstein, Amie E. Hwang, Bing Ma, Guoqin Yu, Laura H. Buchanan, Michael Humphreys, Ann S. Hamilton, John Zadnick, Myles G. Cockburn, James Buxbaum, Heinz-Josef Lenz, Thomas M. Mack, Jacques Ravel, Wendy Cozen. Association between fecal microbiome, diet, and colon adenomas and hyperplastic polyps [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 234. doi:10.1158/1538-7445.AM2017-234