Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Mar 1;74(5):1311-8.
doi: 10.1158/0008-5472.CAN-13-1865. Epub 2014 Jan 2.

Fusobacterium in colonic flora and molecular features of colorectal carcinoma

Tomomitsu Tahara  1 , Eiichiro Yamamoto, Hiromu Suzuki, Reo Maruyama, Woonbok Chung, Judith Garriga, Jaroslav Jelinek, Hiro-o Yamano, Tamotsu Sugai, Byonggu An, Imad Shureiqi, Minoru Toyota, Yutaka Kondo, Marcos R H Estécio, Jean-Pierre J Issa
Affiliations

Fusobacterium in colonic flora and molecular features of colorectal carcinoma

Tomomitsu Tahara et al. Cancer Res. .

Abstract

Fusobacterium species are part of the gut microbiome in humans. Recent studies have identified overrepresentation of Fusobacterium in colorectal cancer tissues, but it is not yet clear whether this is pathogenic or simply an epiphenomenon. In this study, we evaluated the relationship between Fusobacterium status and molecular features in colorectal cancers through quantitative real-time PCR in 149 colorectal cancer tissues, 89 adjacent normal appearing mucosae and 72 colonic mucosae from cancer-free individuals. Results were correlated with CpG island methylator phenotype (CIMP) status, microsatellite instability (MSI), and mutations in BRAF, KRAS, TP53, CHD7, and CHD8. Whole-exome capture sequencing data were also available in 11 cases. Fusobacterium was detectable in 111 of 149 (74%) colorectal cancer tissues and heavily enriched in 9% (14/149) of the cases. As expected, Fusobacterium was also detected in normal appearing mucosae from both cancer and cancer-free individuals, but the amount of bacteria was much lower compared with colorectal cancer tissues (a mean of 250-fold lower for Pan-fusobacterium). We found the Fusobacterium-high colorectal cancer group (FB-high) to be associated with CIMP positivity (P = 0.001), TP53 wild-type (P = 0.015), hMLH1 methylation positivity (P = 0.0028), MSI (P = 0.018), and CHD7/8 mutation positivity (P = 0.002). Among the 11 cases where whole-exome sequencing data were available, two that were FB-high cases also had the highest number of somatic mutations (a mean of 736 per case in FB-high vs. 225 per case in all others). Taken together, our findings show that Fusobacterium enrichment is associated with specific molecular subsets of colorectal cancers, offering support for a pathogenic role in colorectal cancer for this gut microbiome component.

PubMed Disclaimer

Figures

Fig.1
Fig.1
Over-representation of F. nucleatum (left) and pan-fusobacterium (right) in CRC tissues relative to adjacent normal colonic mucosa in 89 paired cases. Statistical analysis was performed using the Wilcoxon signed-rank test.
Fig. 2
Fig. 2
Distribution of Fusobacterium in CRC patients (n=149). The cases were ranked according to the amount of pan-fusobacterium (right=high amount, left=low amount). Note that all F. nucleatum high cases (n=8) were included in pan-fusobacterium high cases (n=14) and there is clear separation of FB high group (n=14, 9.4%) and FB low/negative group (n=135, 90.6%). Red, CIMP1, MLH1 methylated, BRAF, KRAS and TP53 mutated; blue, CIMP2; grey CIMP-negative, MLH1 unmethylated, BRAF, KRAS and TP53 wild type; white, not determined;
Fig. 3
Fig. 3
Number of mutated genes determined by whole exome sequencing analysis in 11 CRCs. (2 FB-high, 6 FB-low/negative CIMP1 and 3 FB-low/negative CIMP2/CIMP-negative). Statistical analysis was performed using One-way ANOVA.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Signat B, Roques C, Poulet P, Duffaut D. Fusobacterium nucleatum in periodontal health and disease. Curr Issues Mol Biol. 2011;13:25–36. - PubMed
    1. Swidsinski A, Dörffel Y, Loening-Baucke V, et al. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum. Gut. 2011;60:34–40. - PubMed
    1. Strauss J, Kaplan GG, Beck PL, et al. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis. 2011;17:1971–1978. - PubMed
    1. Neut C, Bulois P, Desreumaux P, et al. Changes in the bacterial flora of the neoterminal ileum after ileocolonic resection for Crohn’s disease. Am J Gastroenterol. 2002;97:939–946. - PubMed
    1. Ohkusa T, Sato N, Ogihara T, Morita K, Ogawa M, Okayasu I. Fusobacterium varium localized in the colonic mucosa of patients with ulcerative colitis stimulates species-specific antibody. J Gastroenterol Hepatol. 2002;17:849–853. - PubMed

Publication types

MeSH terms