Abstract:
Colorectal cancer (CRC) is a major burden for the Public Health worldwide. It has been proposed that CRC has an infectious aetiology but no statistical association has been observed between disease and microbial species. On the other hand, modification of the relative prevalence of the micro-organisms present in the patient’s gut (dysbiosis) has been shown to be linked to an increased risk of CRC. Nevertheless, the connection between dysbiosis and CRC is still poorly recognized, thus there is the need for further investigation.
I analysed collectively 24 patients with matched normal/cancer tissues using Illumina-based massively parallel sequencing (MPS). I used Fisher’s exact test (FET) to assess the direct association between the presence of a viral species of family and the risk of CRC. I then estimate the viral richness, that is the number of viral species in a sample, using the Shannon index.
I identified 773 viral species present only in the abnormal tissues out of the 1,218 identified (63.4%); this corresponded to 30 families present only in abnormal samples out of the 73 identified (41.1%). There was a high preponderance of Siphoviridae and Myoviridae families (both including bacteriophage species) in cancerous tissues. There was no association between presence of a viral species or family with CRC (FET p-val >0.05) but cancerous tissues displayed a higher Shannon index than the normal tissues (6.5 vs 4.5). Rarefaction analysis confirmed the higher viral richness in abnormal tissues compared to the normal tissues.
Collectively, these data supported the notion that it is not the infection per se that is linked to CRC but rather the relative modification of the the viral species resident in the patient’s gut. I confirmed the relevance of bacteriophages, rather than human oncogenic viruses such as Human Papillomavirus or JC virus, in cancerous samples and I observed an enrichment of Myoviridae in CRC. In conclusion, these data supported and extend the notion that dysbiosis is associated with an increased risk of CRC and strengthened the case for further investigation of the role of bacteriophages in human cancer.
