Abstract

BackgroundNumerous cancers have been linked to microorganisms. Given that colorectal cancer is a leading cause of cancer deaths and the colon is continuously exposed to a high diversity of microbes, the relationship between gut mucosal microbiome and colorectal cancer needs to be explored. Metagenomic studies have shown an association between Fusobacterium species and colorectal carcinoma. Here, we have extended these studies with deeper sequencing of a much larger number (n = 130) of colorectal carcinoma and matched normal control tissues. We analyzed these data using co-occurrence networks in order to identify microbe-microbe and host-microbe associations specific to tumors.ResultsWe confirmed tumor over-representation of Fusobacterium species and observed significant co-occurrence within individual tumors of Fusobacterium, Leptotrichia and Campylobacter species. This polymicrobial signature was associated with over-expression of numerous host genes, including the gene encoding the pro-inflammatory chemokine Interleukin-8. The tumor-associated bacteria we have identified are all Gram-negative anaerobes, recognized previously as constituents of the oral microbiome, which are capable of causing infection. We isolated a novel strain of Campylobacter showae from a colorectal tumor specimen. This strain is substantially diverged from a previously sequenced oral Campylobacter showae isolate, carries potential virulence genes, and aggregates with a previously isolated tumor strain of Fusobacterium nucleatum.ConclusionsA polymicrobial signature of Gram-negative anaerobic bacteria is associated with colorectal carcinoma tissue.

Highlights

  • Numerous cancers have been linked to microorganisms

  • After quality filtering of the raw sequence data and removal of human sequences, microbial sequence diversity was assessed by counting read pairs having unique alignments to genomes of specific bacterial genera, using an in-house database populated with all microbial genome sequences available from GenBank [22] and the Human Microbiome Project [35]

  • A high-throughput sequence screen of Metatranscriptome data from CRC and matched control tissues has revealed differently abundant microbial genome sequence signatures of significance in tumor samples, including those belonging to the Fusobacterium, Campylobacter and Leptotrichia genera

Read more

Summary

Introduction

Numerous cancers have been linked to microorganisms. Given that colorectal cancer is a leading cause of cancer deaths and the colon is continuously exposed to a high diversity of microbes, the relationship between gut mucosal microbiome and colorectal cancer needs to be explored. A link between H. pylori infection and Metagenomic analysis, whereby the presence of a microbe in a sample is inferred from the presence of its sequence signature, has become a sensitive method for identifying novel tumor-associated microbes in a culture-independent manner [2,3]. We used this method to evaluate 11 subjects with colorectal carcinoma and identified substantial over-representation of sequences mapping to Fusobacterium nucleatum (F. nucleatum) in colorectal carcinoma (CRC) tissue compared to adjacent non-tumor gut mucosal control tissue from the same subjects [4]. An association between Fusobacterium spp. abundance and metastasis was observed in the above studies [4,5], and a new study has found an association between Fusobacterium spp. and colorectal adenomas [6]

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call