Intest Res.  2018 Jul;16(3):346-357. 10.5217/ir.2018.16.3.346.

Impact of microbiota in colorectal carcinogenesis: lessons from experimental models

Affiliations
  • 1Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
  • 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • 3Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan. yhni@ntu.edu.tw

Abstract

A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC.

Keyword

Colorectal neoplasms; Microbiota dysbiosis; Mucosa-associated bacteria; Pathobiont; Virulence

MeSH Terms

Adenoma
Animals
Bacteria
Bacteroides fragilis
Carcinogenesis*
Colon
Colorectal Neoplasms
Enterotoxins
Escherichia coli
Fecal Microbiota Transplantation
Fusobacterium nucleatum
Gastrointestinal Microbiome
Healthy Volunteers
Humans
Mice
Microbiota*
Models, Theoretical*
Mutagens
Rats
Virulence
Virulence Factors
Enterotoxins
Mutagens
Virulence Factors
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