Fusobacterium nucleatum is a common oral bacterium that is enriched in colorectal adenomas and adenocarcinomas (CRC). In humans, high fusobacterial CRC abundance is associated with chemoresistance and poor prognosis. In animal models, fusobacteria accelerate CRC progression. Targeting F. nucleatum may reduce fusobacteria cancer progression and therefore determining the origin of CRC F. nucleatum and the route by which it reaches colon tumors is of biologic and therapeutic importance. Arbitrarily primed PCR performed previously on matched same-patients CRC and saliva F. nucleatum isolates, suggested that CRC F. nucleatum may originate from the oral cavity. However, the origin of CRC fusobacteria as well as the route of their arrival to the tumor have not been well-established. Herein, we performed and analyzed whole genome sequencing of paired, same-patient oral, and CRC F. nucleatum isolates and confirmed that CRC-fusobacteria originate from the oral microbial reservoir. Oral fusobacteria may translocate to CRC by descending via the digestive tract or using the hematogenous route during frequent transient bacteremia caused by chewing, daily hygiene activities, or dental procedures. Using the orthotropic CT26 mouse model we previously showed that IV injected F. nucleatum colonize CRC. Here, we compared CRC colonization by gavage vs. intravenous inoculated F. nucleatum in the MC38 and CT26 mouse orthotropic CRC models. Under the tested conditions, hematogenous fusobacteria were more successful in CRC colonization than gavaged ones. Our results therefore provide evidence that the hematogenous route may be the preferred way by which oral fusobacteria reach colon tumors.

核梭菌是一种常见的口腔细菌，富含大肠腺瘤和腺癌（CRC）。在人类中，高浓度的梭菌CRC与化学耐药性和不良预后有关。在动物模型中，梭菌会加速CRC进程。指定目标核 可能会减少梭菌的癌症进展，因此确定CRC的起源 核它到达结肠肿瘤的途径具有生物学和治疗意义。先前对匹配的相同患者CRC和唾液进行了任意引物PCR核 分离株，提示CRC 核可能来自口腔。然而，CRC梭菌的起源以及它们到达肿瘤的途径还没有被确定。在这里，我们进行并分析了配对，同病患者口服和CRC的全基因组测序核分离并证实CRC融合细菌起源于口腔微生物库。在因咀嚼，日常卫生活动或牙科操作引起的频繁的短暂菌血症期间，口腔融合细菌可能会通过消化道下降或使用血源性途径而易位为CRC。使用正交各向异性CT26小鼠模型，我们先前已经证明了静脉注射核殖民CRC。在这里，我们比较了管饲法和静脉接种法对CRC的定植核在MC38和CT26小鼠正交各向异性CRC模型中。在测试条件下，血源性梭菌在CRC定植中比在空袭中更成功。因此，我们的结果提供了证据，即血源性途径可能是口腔fusobacteria通过细菌到达结肠肿瘤的首选途径。