Tumor Biology

, Volume 34, Issue 3, pp 1285–1300 | Cite as

The role of gut microbiota in the pathogenesis of colorectal cancer

Review

Abstract

The human gastrointestinal tract harbors a complex and abundant microbial community that can reach levels as high as 1013–1014 microorganisms in the colon. These microorganisms are essential to a host’s well-being in terms of nutrition and mucosa immunity. However, numerous studies have also implicated members of the colonic microbiota in the development of colorectal cancer (CRC). While CRC involves a genetic component where damaged DNA and genetic instability initiates a malignant transformation, environmental factors can also contribute to the onset of CRC. Furthermore, considering the constant exposure of the colonic mucosa to the microbiome and/or its metabolites, the mucosa has long been proposed to contribute to colon tumorigenesis. However, the mechanistic details of these associations remain unknown. Fortunately, due to technical and conceptual advances, progress in characterizing the taxonomic composition, metabolic capacity, and immunomodulatory activity of human gut microbiota have been made, thereby elucidating its role in human health and disease. Furthermore, the use of experimental animal models and clinical/epidemiological studies of environmental etiological factors has identified a correlation between gut microbiota composition and gastrointestinal cancers. Bacteria continuously stimulate activated immunity in the gut mucosa and also contribute to the metabolism of bile and food components. However, the highest levels of carcinogen production are also associated with gut anaerobic bacteria and can be lowered with live lactobacilli supplements. In this review, evidence regarding the relationship between microbiota and the development of CRC will be discussed, as well as the role for microbial manipulation in affecting disease development.

Keywords

Gut microbiota Colorectal cancer Inflammation Bacterial enzymes Metabolites Probiotic 

Abbreviations

CRC

Colorectal cancer

PCA

Principle component analysis

IBD

Inflammatory bowel diseases

TGF-β

Transforming growth factor-β

ETBF

Enterotoxigenic Bacteroides fragilis

CECs

Colonic epithelial cells

BFT

B. fragilis toxin

PRRs

Pattern recognition receptors

PAMPs

Pathogen-associated molecular patterns

TLRs

Toll-like receptors

NLRs

Nod-like receptors

NF-κB

Nuclear factor κB

DMH

Dimethylhydrazine

SIGIRR

Single immunoglobulin IL-1 receptor-related molecule

STAT3

Signal transducer and activator of transcription

MAM

Metabolite methylazoxymethanol

DCA

Deoxycholic acid

LCA

Lithocholic acid

FBA

Fecal bile acid

PGE2

Prostaglandin E2

NOC

Nitroso compounds

IFN-γ

Interferon-γ

TNF-α

Tumor necrosis factor-α

CFU

Colony-forming units

GI

Gastrointestinal

ROI

Reactive oxygen intermediate

H2S

Hydrogen sulfide

Notes

Acknowledgments

We thank Dr. Huanlong Qin for his critical reading of this manuscript.

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Qingchao Zhu
    • 1
  • Renyuan Gao
    • 1
  • Wen Wu
    • 1
  • Huanlong Qin
    • 1
  1. 1.Department of SurgeryThe Sixth People’s Hospital Affiliated to Shanghai Jiao Tong UniversityShanghaiPeople’s Republic of China

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