Screening metatranscriptomes for toxin genes as functional drivers of human colorectal cancer

• Published in: Baillière's best practice & research. Clinical gastroenterology Vol. 27; no. 1; pp. 85 - 99
• Main Authors: Dutilh, Bas E., Ph.D, Backus, Lennart, M.Sc, van Hijum, Sacha A.F.T., Ph.D, Tjalsma, Harold, Ph.D
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2013; Elsevier Limited
• Subjects: Bacteria; Bacterial driver-passenger model; Biomarkers; Colorectal cancer; Colorectal Neoplasms - genetics; Disease; DNA damage; E coli; Enterotoxigenic Bacteroides fragilis; Enterotoxins - genetics; Escherichia coli colibactin; Gastroenterology and Hepatology; Gastrointestinal Tract - microbiology; Gene Expression - physiology; Genes; Host-Pathogen Interactions; Humans; Intestinal Mucosa - microbiology; Metagenome - physiology; Metagenomics; Microbiology; Transcriptome - genetics; Tumors; Metagenomics; Bacterial driver-passenger model; Escherichia coli colibactin; Enterotoxigenic Bacteroides fragilis; Colorectal cancer
• ISSN: 1521-6918; 1532-1916
• DOI: 10.1016/j.bpg.2013.03.008

Abstract The colonic mucosa is in constant physical interaction with a dense and complex bacterial community that comprises health-promoting and pathogenic microbes. Here, we highlight important clinical studies and experimental models that have linked the intestinal microbiota to the development of colorectal cancer (CRC). Moreover, we use recently published metatranscriptome sequencing data to test whether potentially carcinogenic toxin genes exhibit higher expression levels in human CRC tissue compared to adjacent non-malignant mucosa. Our analyses show a large variation in expression of toxin(-related) genes from different species. Surprisingly, Enterobacterial toxins were among the highest expressed, while Enterobacteria were not among the most abundant species in these samples. Although we can differentiate on- and off-tumour sites based on toxin reads, the read depth profiles are quite similar and show only limited coverage of the toxin genes. Thus, extended metagenomic studies are needed to obtain a high-resolution picture of host–pathogen interactions during human CRC.