Intest Res 2018; 16(3): 346-357  https://doi.org/10.5217/ir.2018.16.3.346
Impact of microbiota in colorectal carcinogenesis: lessons from experimental models
Linda Chia-Hui Yu1, Shu-Chen Wei2, Yen-Hsuan Ni3
1Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Departments of 2Internal Medicine and 3Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
Correspondence to: Yen-Hsuan Ni, Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei 100, Taiwan. Tel: +886-2-23123456 (ext. 71516), Fax: +886-2-23938871, E-mail: yhni@ntu.edu.tw
Received: March 26, 2018; Revised: May 28, 2018; Accepted: May 29, 2018; Published online: July 30, 2018.
© Korean Association for the Study of Intestinal Diseases. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: Colorectal neoplasms; Microbiota dysbiosis; Mucosa-associated bacteria; Pathobiont; Virulence


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