Homing of Oral Fusobacteria to Colon Cancer

Introduction

Fusobacterium nucleatum is an oral anaerobe that rise in numbers during the development of periodontal disease. Recent studies found fusobacterial enrichment in colorectal adenocarcinoma (CRC). Fusobacterial presence in CRC is associated with tumor acceleration, drug resistance and poor disease outcome. We showed previously that fusobacteria use the Fap2 lectin to specifically attach to CRC-displayed Gal-GalNAc. However, the source and route enabling fusobacteria localization to CRC have been unclear.

Materials and methods

For investigating the oral origin of CRC fusobacteria, Fusobacterium nucleatum was isolated from saliva collected one day before resection and from colonic adenocarcinomas obtained from the same patient. Genomic DNA was extracted from the oral and matching CRC isolates, sequenced and compared.

For comparison of CRC colonization by fusobacteria inoculated by oral gavage versus intravascularly inoculated, the C57BL/6 mouse MC-38 colon orthotopic rectal cancer model was used.

Results and discussion

Genomic sequences of fusobacteria isolated from matched oral and CRC samples indicated that CRC fusobacteria are from oral origin. Quantification of CRC colonization of orally or IV inoculated fusobacteria demonstrate that oral fusobacteria translocate to CRC via the hematogenous route.

Transient bacteremia by oral bacteria is frequent during periodontal disease, enabling easy access of oral fusobacteria to the blood.

Conclusion

Our results indicate that CRC-fusobacteria originate from the oral microbial reservoir and provide evidence that they reach colon tumors via the bloodstream. Our results also suggest that fusobacteria have potential as a tumor-homing vehicle to treat colon cancer.