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Review
. 2020 Nov 9;12(1):1800898.
doi: 10.1080/19490976.2020.1800898.

Bacteria-related changes in host DNA methylation and the risk for CRC

Iradj Sobhani  1 , Hugo Rotkopf  2 , Khashayarsha Khazaie  3
Affiliations
Review

Bacteria-related changes in host DNA methylation and the risk for CRC

Iradj Sobhani et al. Gut Microbes. .

Abstract

Colorectal cancer (CRC) is the second most common cause of cancer deaths in men and women combined. Colon-tumor growth is multistage and the result of the accumulation of spontaneous mutations and epigenetic events that silence tumor-suppressor genes and activate oncogenes. Environmental factors are primary contributors to these somatic gene alterations, which account for the increase in incidence of CRC in western countries. In recent decades, gut microbiota and their metabolites have been recognized as essential contributing factors to CRC, and now serve as biomarkers for the diagnosis and prognosis of CRC. In the present review, we highlight holistic approaches to understanding how gut microbiota contributes to CRC. We particularly focus herein on bacteria-related changes in host DNA methylation and the risk for CRC.

Keywords: Colon; cancer; methylation; microbiota; mutation.

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Figures

Figure 1.
Figure 1.
Frequency and type of mutations in human CRC tissues.
Figure 2.
Figure 2.
Mechanisms of DNA demethylation. (a) Passive demethylation. This process occurs during replication, wherein one or more limiting factors (i.e., compromised DNMT function, absence of SAM) prevents methylation maintenance and results in the subsequent loss of 5mC residues. (b) Active demethylation. The figure shows TET enzymes (TET1, TET2, or TET3) (teal) catalyzing stepwise oxidation of 5mC, which is first converted into 5-hydoxymethylcytosine (5hmC), further oxidized into 5-formylcytosine (5fC), and finally converted into 5-carbocylcytosine (5caC). 5fC and 5caC intermediates can be recognized and removed by thymine DNA glycosylase (TDG) (violet). They are then replaced with an unmethylated cytosine nucleotide to complete the base excision repair (BER) process (figure from ref).
Figure 3.
Figure 3.
IEC: intestinal epithelial cell; SIEC: small; IECL: IEC large intestine; CV: conventional; GF: germ-free; IEC: intestinal epithelial cell; SIEC:small; LIEC: large intestine; CV:conventional; GF: germ-free; from Takashi et al Ref. .
See this image and copyright information in PMC

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