Cancer has long been considered a genetic disease. However, accumulating evidence supports the involvement of infectious agents in the development of cancer, especially in those organs that are continuously exposed to microorganisms, such as the large intestine. Recent next-generation sequencing studies of the intestinal microbiota now offer an unprecedented view of the aetiology of sporadic colorectal cancer and have revealed that the microbiota associated with colorectal cancer contains bacterial species that differ in their temporal associations with developing tumours. Here, we propose a bacterial driver–passenger model for microbial involvement in the development of colorectal cancer and suggest that this model be incorporated into the genetic paradigm of cancer progression.
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Cell Communication and Signaling Open Access 28 June 2023
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Identification of a novel gut microbiota signature associated with colorectal cancer in Thai population
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The authors thank R. Roelofs, G. Kortman and I. Kato for inspiring discussions and the three anonymous referees for their excellent suggestions, which were very useful in shaping the final article. This work was in part supported by the Dutch Cancer Society (KWF; Project KUN 2006–3591) and the Dutch Digestive Diseases Foundation (MDLS; project WO 10–53). B.E.D. was supported by the Dutch Science foundation (NWO; Veni grant 016.111.075). The funding bodies had no role in the study design, data collection and analysis, the decision to publish or the preparation of the manuscript.
The authors declare no competing financial interests.
- Colonic dysbiosis
A local or disseminated change in the composition of the colonic microbiota, often leading to impaired health. Dysbiosis may be either the cause or the consequence of intestinal disease.
- Commensal bacteria
Bacteria living in a mutually advantageous relationship with a host (for example, in the lumen of the gastrointestinal tract).
- COX2 pathway
The regulatory pathway responsible for the formation of important biological regulator molecules, including prostaglandins. The enzyme COX2 is not detectable in most healthy tissues but is upregulated during inflammation and in carcinomas. Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, inhibit the COX2 pathway and decrease the risk of colorectal cancer development.
A subfamily of chemokines that contain a Cys-Xaa-Cys motif. Chemokines are small secreted molecules that function in leukocyte recruitment and activation, and react to different pathological processes, including infectious disease, inflammation and tumorigenesis.
An abnormal proliferation of immature cells.
- Epigenetic mutations
Functionally relevant modifications of the genome that do not involve a change in the nucleotide sequence; for example, changes in DNA methylation or histone deacetylation.
A compound that is capable of causing damage to, or genetic mutations in, DNA; also known as a mutagenic or carcinogenic compound.
A site (within an organ) that has an increased number of cells or an increase in cell proliferation, representing the early phases of a tumour; also known as a neoplasia, a pre-malignant lesion or a benign tumour.
All of the genetic transcripts (RNA) within a microbiota.
All of the genetic material (DNA) within a microbiota. This can also be referred to as the metagenome of the microbiota.
The complete setof microorganisms that are present in a particular environment or community.
- Probiotic organisms
Microorganisms that have effects which are thought to be beneficial to the health of the host when the microorganism in question is present in adequate amounts.
Growth substrates that are preferentially (or ideally, exclusively) metabolized by a single probiotic genus or species and may thus be used as dietary supplements to promote targeted growth of these microorganisms.
The process by which a new tumour is produced.
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Tjalsma, H., Boleij, A., Marchesi, J. et al. A bacterial driver–passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol 10, 575–582 (2012). https://doi.org/10.1038/nrmicro2819
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