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Review
. 2020 Jul;27(4):9-21.
doi: 10.21315/mjms2020.27.4.2. Epub 2020 Aug 19.

The Mechanism of Bacteroides fragilis Toxin Contributes to Colon Cancer Formation

Wai Teng Cheng  1 , Haresh Kumar Kantilal  2 , Fabian Davamani  1
Affiliations
Review

The Mechanism of Bacteroides fragilis Toxin Contributes to Colon Cancer Formation

Wai Teng Cheng et al. Malays J Med Sci. 2020 Jul.

Abstract

The Bacteroides fragilis (B. fragilis) produce biofilm for colonisation in the intestinal tract can cause a series of inflammatory reactions due to B. fragilis toxin (BFT) which can lead to chronic intestinal inflammation and tissue injury and play a crucial role leading to colorectal cancer (CRC). The enterotoxigenic B. fragilis (ETBF) forms biofilm and produce toxin and play a role in CRC, whereas the non-toxigenic B. fragilis (NTBF) does not produce toxin. The ETBF triggers the expression of cyclooxygenase (COX)-2 that releases PGE2 for inducing inflammation and control cell proliferation. From chronic intestinal inflammation to cancer development, it involves signal transducers and activators of transcription (STAT)3 activation. STAT3 activates by the interaction between epithelial cells and BFT. Thus, regulatory T-cell (Tregs) will activates and reduce interleukin (IL)-2 amount. As the level of IL-2 drops, T-helper (Th17) cells are generated leading to increase in IL-17 levels. IL-17 is implicated in early intestinal inflammation and promotes cancer cell survival and proliferation and consequently triggers IL-6 production that activate STAT3 pathway. Additionally, BFT degrades E-cadherin, hence alteration of signalling pathways can upregulate spermine oxidase leading to cell morphology and promote carcinogenesis and irreversible DNA damage. Patient with familial adenomatous polyposis (FAP) disease displays a high level of tumour load in the colon. This disease is caused by germline mutation of the adenomatous polyposis coli (APC) gene that increases bacterial adherence to the mucosa layer. Mutated-APC gene genotype with ETBF increases the chances of CRC development. Therefore, the colonisation of the ETBF in the intestinal tract depicts tumour aetiology can result in risk of hostility and effect on human health.

Keywords: Bacteroides fragilis; Bacteroides fragilis toxin; STAT3 pathway; colon cancer; inflammation.

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Conflict of interest statement

Conflict of Interest None.

Figures

Figure 1
Figure 1
The mechanism of carcinogenesis through abnormal intestinal immune system
Figure 2
Figure 2
The role of the signalling pathways when epithelial cells contact BFT
Figure 3
Figure 3
Normal condition of the SMO and ROS that helps in immune response and cell signalling pathways
Figure 4
Figure 4
The adverse effect of SMO contacted BFT
See this image and copyright information in PMC

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