Recent metagenomic studies have discovered gut microbiome signatures in colonic
tissues from patients with colorectal cancer or adenomas, suggesting a potential causal link
between gut microbiome and the development of colorectal neoplasia. Diet clearly plays an
important etiological role in colon carcinogenesis. It is long believed that diet is a major
determinant of the human gut microbiota composition. Three recent landmark studies have
provided compelling evidence supporting this notion, each having found similar microbiome core
signatures. Furthermore, human gut microbiome signature or ?enterotype? is strongly associated
with an individual?s long-term diet pattern, but not with short-term dietary changes. To date, few
studies have comprehensively examined the complex interplay of fecal microbiome, diet, and
risk of colon adenoma. Therefore, we propose a metagenomic molecular epidemiology study to
address our hypothesis that diet-associated gut microbiome signatures are associated with risk
of colon adenoma. This proposal builds upon a relatively large cohort of patients undergoing
screening colonoscopy who are being recruited into the parent GI SPORE project for a stool-
based methylation biomarker study for early detection of colon adenomas. We aim to: 1)
indentify gut microbiome signatures associated with habitual diet; 2) examine the association of
gut microbiome signatures with risk of colon adenoma; and 3) assess direct and gut
microbiome-mediated effects of diet on risk of colon adenoma. These aims will be accomplished
by using the existing Cleveland Risk Factors and Early Detection of Colon Adenoma cohort
population, where rich dietary and epidemiological data and pre-screening stool samples are
being collected from 1,600 average-risk patients as part of parent Case GI SPORE program.
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