Genomic analysis identifies association of Fusobacterium with colorectal carcinoma

Abstract

The tumor microenvironment of colorectal carcinoma is a complex community of genomically altered cancer cells, nonneoplastic cells, and a diverse collection of microorganisms. Each of these components may contribute to carcinogenesis; however, the role of the microbiota is the least well understood. We have characterized the composition of the microbiota in colorectal carcinoma using whole genome sequences from nine tumor/normal pairs. Fusobacterium sequences were enriched in carcinomas, confirmed by quantitative PCR and 16S rDNA sequence analysis of 95 carcinoma/normal DNA pairs, while the Bacteroidetes and Firmicutes phyla were depleted in tumors. Fusobacteria were also visualized within colorectal tumors using FISH. These findings reveal alterations in the colorectal cancer microbiota; however, the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation.

Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome

“…The results of this study confirm for the first time in European cohorts previous reports from North America [20,21] that Fn is over-represented in tumour tissue compared to normal tissue in colorectal cancers. More strikingly this work indicates that Fn load increases with disease progression from adenoma to cancer and may also be related to survival from cancer.…”

“…showed over-representation of Fusobacterium nucleatum (Fn) in CRC tumours versus surrounding normal tissue [20,21]. Fn is a highly invasive, gram-negative anaerobic bacterium and part of the oral and gut commensal flora [22] that has been linked to several diseases, such as periodontitis [23], appendicitis [24], Lemierre's disease [25], and inflammatory bowel disease [26].…”

Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features

“…In relatively recent publications, authors have described associations between species of bacteria, such as Streptococcus bovis subtypes, 33 and Fusobacterium spp. 34 and colorectal neoplasia. Importantly, the composition of the gut microbiota also varies with gender, 34 and this may be reflected in the distinct distributions of molecular colorectal carcinoma subtypes seen in male and female subjects.…”

“…34 and colorectal neoplasia. Importantly, the composition of the gut microbiota also varies with gender, 34 and this may be reflected in the distinct distributions of molecular colorectal carcinoma subtypes seen in male and female subjects. A possible explanation for the bimodal distribution of colorectal carcinoma, we observed is that the contact of the large bowel mucosa with luminal contents may last longer in both extremities of the colon than in the mid-colon.…”

Human Fecal Microbiome–Based Biomarkers for Colorectal Cancer

“…In recent years, several groups have appreciably expanded the evidence linking infectious agents to colonic disease development (reviewed in ref. 10). These microorganisms are thought to create a microenvironment more favorable to colorectal cancer development.…”