Yannick Eisele

interaction with cancer epithelial cells suggests that its role in human health and disease warrants further investigation.

Abstract 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 and associated methylome of this organism and phylogenetically confirm its classification into the Fusobacterium genus, with F. perfoetens as its closest neighbor. Fs is phenotypically and genetically distinct, with morphological analysis revealing its coccoid shape, that while similar to F. perfoetens is rare for most Fusobacterium members. 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 >20,000 human metagenomic samples shows that it is a low-prevalence member within human stool with variable relative abundance, found in both healthy controls and patients with colorectal cancer (CRC). Our study sheds light on a novel bacterial species isolated directly from the human CRC tumor niche, and given its interaction with cancer epithelial cells suggests that its role in human health and disease warrants further investigation.

Abstract 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.