's link to colorectal neoplasia sequenced: A systematic review and future insights.

AIM

To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development.

METHODS

Two independent investigators systematically reviewed all original scientific articles published between January, 2000, and July, 2017, using PubMed, EMBASE, and MEDLINE. A total of 355 articles were screened at the abstract level. Of these, only original scientific human, animal, and in vitro studies investigating and its relationship with colorectal cancer (CRC) were included in the analysis. Abstracts, review articles, studies investigating other colonic diseases, and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates, resolving disagreements between the two reviewers, and applying the above criteria.

RESULTS

Studies have consistently identified positive associations between , especially (), and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and CpG island methylator phenotype (CIMP)-high CRCs. There was evidence of temporality and a biological gradient, with increased DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic enrichment; evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of DNA in CRC tissue. The pathophysiology of enrichment of and other species in colonic tissue is unclear; however, the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin (Gal-GalNAc) in the colonic epithelium may also mediate attachment to CRC and precursors through interaction with an protein, fibroblast activation protein 2 (FAP2). The clinical significance of detection or enrichment of in colorectal neoplasia is ambiguous, but data suggest a procarcinogenic effect of , likely due to activation of oncogenic and inflammatory pathways and modulation of the tumor immune environment. This is hypothesized to be mediated by certain strains carrying invasive properties and virulence factors such as FadA and FAP.

CONCLUSION

Evidence suggests a potential active role of , specifically , in CRC. Future prospective and experimental human studies would fill an important gap in this literature.