Abstract 238: Evidence of early colorectal cancer risk and prevention pathways in the fecal microbiome of colonoscopy patients: associations with diet and circulating adipocytokines
Authors: Daniel Carrie R. , Hoffman Kristi L. , Raju G S. , Hanash Samir M. , Hutchinson Diane S. , Ajami Nadim J. , Fowler Richard G. , Browman Gladys J. , Sood Akhil , Scheet Paul , Wu Xifeng , Petrosino Joseph F. 
Published: July 2017

Abstract
Accumulating evidence suggests that the gut microbiome’s role in early colorectal cancer etiology extends beyond the pro-carcinogenic activities of specific pathogens and is largely influenced by the wider microbial community of commensal bacteria. To identify early microbiome-related pathways and potential dietary intervention targets, we conducted an epidemiologic study among cancer-free colonoscopy patients at known and varied risk of colorectal neoplasia. Sporadic patients undergoing colonoscopy screening provided consent and fasting blood. Polyps, if found, were removed at colonoscopy and ~1 month later (prior studies show the effect of the colonoscopy prep dissipates within this time period), eligible patients provided a stool sample via mail kit (n=47). Patients completed comprehensive dietary assessments and clinicopathologic factors, including screening history, were abstracted from electronic medical records. We characterized the fecal microbiome via whole genome shotgun sequencing (Illumina HiSeq) and circulating blood adipocytokines via Luminex multiplex assays (Millipore). Majority of the patients were female and recently diagnosed with precancerous polyps, primarily tubular and sessile serrated adenomas. Polyp patients were more likely to be obese and to not consume alcohol, but otherwise similar by age, diet composition, and other risk factors to patients with normal colonoscopy findings. We observed no effects of time interval between colonoscopy and fecal sample collection, or of recent polyp diagnosis/removal, on microbial alpha or beta diversity. Correlation networks between species revealed that Faecalibacterium prausnitzii inversely correlated with E. coli, the most abundant species in our sample, and co-occurred with other short chain fatty acid-metabolizing bacteria, including Anaerostipes hadrus and Roseburia hominis, known butyrate-producers. Among recurrent patients (n=14), Bacteroides fragilis co-occurred with Bilophila wadsworthia (r=0.6; P=0.02). Higher intake of fiber and/or overall diet quality, as defined by the Healthy Eating Index, was associated with several bacteria largely linked to butyrate production (e.g., Bifidobacterium animalis, F. prausnitzii, Roseburia intestinalis, Coprococcus eutactus, Eubacterium eligens). These same dietary factors were inversely correlated with Blautia hydrogenotrophica, an acetogen, and other bacteria implicated in inflammation and colorectal cancer (e.g., B. fragilis). Biologically plausible associations between microbial (functional gene content) pathways important to cancer risk (e.g., one-carbon, lysine, carbohydrate and fatty acid metabolism) with dietary factors and circulating adipocytokines involved in immunity, inflammation, and glucose metabolism support the functionality of these diet-microbe relationships.
Citation Format: Carrie R. Daniel, Kristi L. Hoffman, G S. Raju, Samir M. Hanash, Diane S. Hutchinson, Nadim J. Ajami, Richard G. Fowler, Gladys J. Browman, Akhil Sood, Paul Scheet, Xifeng Wu, Joseph F. Petrosino. Evidence of early colorectal cancer risk and prevention pathways in the fecal microbiome of colonoscopy patients: associations with diet and circulating adipocytokines [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 238. doi:10.1158/1538-7445.AM2017-238