Mayo Clinic - Fecal Microbiota and Adenomas

Background: Adenomatous polyps are the most common precursor to colorectal cancer (CRC), the second leading cause of cancer death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. Methods: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n=233) and without (n=547). Results: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, pro-inflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Many of our findings were consistent with previously reported shifts in the gut microbiota of CRC patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. Conclusions: These data suggest that diets rich in refined sugar, protein, and lipids may lead to increased bile acid production, creating a colonic environment that promotes the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio. In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, catalyzing adenoma development and eventually CRC. Impact: This study suggests a plausible biological mechanism to explain the links between diet, shifts in the microbiota, and CRC. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of CRC and may facilitate personalized therapeutics focused on the microbiota.]]>
Inclusion critera: Adults 50-80 years old undergoing standard screening colonoscopy Exclusion criteria: Premenopausal women Hematochezia or melena within the month prior to enrollment Prior colorectal resection Coagulopathy or anticoagulant use Chemotherapy within 3 months of enrollment Contraindications to colonoscopy Inability to desist from therapeutic doses of nonsteroidal anti-inflammatory drugs Aerodigestive cancer within 5 years of enrollment A fecal occult blood test within the year prior to enrollment Colorectal evaluation (e.g., sigmoidoscopy or colonoscopy) within 10 years of enrollment Patients at high risk for CRC-including patients with familial adenomatous polyposis, cancer syndromes, inflammatory bowel disease, prior CRC or adenomas, or ≥2 first-degree relatives with CRC ]]>
The original study (fecal collection) was conducted between 2001-2005 at multiple medical centers around the United States. Patients who presented for standard colonoscopic screenings submitted self-collected fecal samples that were shipped on ice overnight to Mayo Clinic, Rochester, MN. After sample collection, patients went on to colonoscopy and were included in the study if they were diagnosed as having healthy (polyp-free) colons, adenomas (>1cm), or colorectal cancer. Fecal samples were stored at -80C until processing. In 2014, DNA from fecal samples was extracted and submitted for 16S sequencing.]]>