<h3>Objective</h3> Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. <i>Fusobacterium nucleatum</i> may promote colorectal tumour growth and inhibit T cell-mediated immune responses against colorectal tumours. Thus, we hypothesised that the amount of <i>F. nucleatum</i> in colorectal carcinoma might be associated with worse clinical outcome. <h3>Design</h3> We used molecular pathological epidemiology database of 1069 rectal and colon cancer cases in the Nurses’ Health Study and the Health Professionals Follow-up Study, and measured <i>F. nucleatum</i> DNA in carcinoma tissue. Cox proportional hazards model was used to compute hazard ratio (HR), controlling for potential confounders, including microsatellite instability (MSI, mismatch repair deficiency), CpG island methylator phenotype (CIMP), <i>KRAS</i>, <i>BRAF</i>, and <i>PIK3CA</i> mutations, and LINE-1 hypomethylation (low-level methylation). <h3>Results</h3> Compared with <i>F. nucleatum</i>-negative cases, multivariable HRs (95% CI) for colorectal cancer-specific mortality in <i>F. nucleatum</i>-low cases and <i>F. nucleatum</i>-high cases were 1.25 (0.82 to 1.92) and 1.58 (1.04 to 2.39), respectively, (p for trend=0.020). The amount of <i>F. nucleatum</i> was associated with MSI-high (multivariable odd ratio (OR), 5.22; 95% CI 2.86 to 9.55) independent of CIMP and <i>BRAF</i> mutation status, whereas CIMP and <i>BRAF</i> mutation were associated with <i>F. nucleatum</i> only in univariate analyses (p&lt;0.001) but not in multivariate analysis that adjusted for MSI status. <h3>Conclusions</h3> The amount of <i>F. nucleatum</i> DNA in colorectal cancer tissue is associated with shorter survival, and may potentially serve as a prognostic biomarker. Our data may have implications in developing cancer prevention and treatment strategies through targeting GI microflora by diet, probiotics and antibiotics.

Fusobacterium nucleatumin colorectal carcinoma tissue and patient prognosis