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Cancerous tissue is a largely unexplored microbial niche that provides a unique environment for the colonization and growth of specific bacterial communities, and with it, the opportunity to identify novel bacterial species. Here, we report distinct features of a novel Fusobacterium species, F. sphaericum sp. nov. (Fs), isolated from primary colon adenocarcinoma tissue. We acquire the complete, closed genome of this organism and phylogenetically confirm its classification into the Fusobacterium genus. Phenotypic and genomic analysis of Fs reveal that this novel organism is of coccoid shape, rare for Fusobacterium members, and has species-distinct gene content. Fs displays a metabolic profile and antibiotic resistance repertoire consistent with other Fusobacterium species. In vitro, Fs has adherent and immunomodulatory capabilities, as it intimately associates with human colon cancer epithelial cells and promotes IL-8 secretion. Analysis of the prevalence and abundance of Fs in ~1,750 human metagenomic samples shows that it is a moderately prevalent member of the human oral cavity and stool. Intriguingly, analysis of ~1,270 specimens from patients with colorectal cancer demonstrate that Fs is significantly enriched in colonic and tumor tissue as compared to mucosa or feces. Our study sheds light on a novel bacterial species that is prevalent within the human intestinal microbiota and whose role in human health and disease requires further investigation.

Background: Fusobacterium nucleatum (Fn), an oral commensal involved in a wide spectrum of infections, has recently been implicated in colorectal cancer (CRC) etiology. However, the role of Fn in treatment-naïve CRC patients remains unclear. Therefore, we assessed whether Fn abundance is associated with clinicopathologic characteristics among treatment-naïve CRC patients enrolled in the prospective ColoCare Study. Methods: Quantitative real-time PCR was used to amplify and detect Fn DNA in fecal samples collected prior to surgery from 105 patients. We utilized multivariable regression analysis to investigate associations between Fn abundance and sex, age at surgery, BMI, tumor stage, tumor grade, tumor site, infection with H. pylori, microsatellite instability, alcohol consumption, and smoking history by adjusting for sex, age at surgery, cohort, and BMI. Results: Compared to patients with undetectable or low abundance of Fn, patients with higher abundance of Fn were more likely to be diagnosed with rectal cancer than colon cancer (Odds Ratio [OR] = 3.01, 95% CI 1.06-8.57 P=0.04). Categorizing the colon into right-sided (proximal) and left-sided (distal) showed that patients with a high abundance of Fn were also more likely to be diagnosed with rectal cancer compared to right-sided colon cancer (OR=5.32, 95% CI 1.23-22.98 P=0.03), thus suggesting an increasing risk of cancer diagnosis along the bowel towards the rectum. Conclusion: Our study sheds light on the association of high abundance of Fn in fecal biospecimen with colorectal carcinogenesis, which may support future preventive or diagnostic measures. Citation Format: Yannick Eisele, Patrick M. Mallea, Biljana Gigic, W. Zac Stephens, Christy A. Warby, Kate Buhrke, Tengda Lin, Petra Schrotz-King, Sheetal Hardikar, Lyen C. Huang, T. Bartley Pickron, Courtney Scaife, Torsten Koelsch, Anita R. Peoples, Maria A. Pletneva, Mary Bronner, Martin Schneider, Alexis B. Ulrich, Eric A. Swanson, Adetunji T. Toriola, Hans Hauner, June Round, Cornelia M. Ulrich, Andreana N. Holowatyj, Jennifer Ose. Fusobacterium nucleatum and clinicopathologic features of colorectal carcinoma: Results from the ColoCare Study [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A01.