Gagnière, J. et al. Gut microbiota imbalance and colorectal cancer. World J. Gastroenterol.22, 501–518 (2016).
     This 2016 review paper investigated the body of research investigating human gut microbiome imbalances and it's related to colorectal cancer (CRC). The paper investigates 7 bacterial species linked to any stage of CRC, (S. bovis, H. pylori, B. fragillis E. faecalis, C. septicum, Fusobacterium, and E. coli). The two that the paper highlights as the most researched are H. Pylori and S. bovis.
      The paper also details the four suspected mechanisms through which these gut imbalances increase the risk of CRC.
  • Bacterial -derived genotoxins and other bacterial virulence factors:
    • The production of some toxins affect the bacteria's virulence, or the measured pathogenicity by pervasiveness of the host's tissues and organs.
    • Other toxins can affect some host derived signalling pathways which in turn develops environment optimal for carcinogenesis (Inflammation, cell proliferation and DNA damage)
    • Others affect the cell cycle or resist cell-programmed death.
  • MIcrobial -derived metabolism
    • Increased fat intake -> increases bile secretion -> increased risk of CRC
  • Host defense modulation and inflammation
    • Activation of Toll Like Receptors and Nod Like Receptors leads to an pro-inflammatory response
  • Oxidative Stress and anti-oxidative defenses modulation
    • The imbalance of pro-oxidative molecules and anti-oxidative defenses. The imbalances stem primarily from bacterial infection that affect DNA repair systems

The author’s last section talks about what clinical solution could be developed from the current information known about gut imbalances. The authors briefly talk about epigenetics and DNA methylation, in relation to the effectiveness of administering probiotics in decreasing gastrointestinal disease risk. The conclusions also talk about future studies should look on expanding the possible connections between molecular pathways leading to carcinogenesis and methylation in CpG islands.

     The discussion about DNA methylation is a good start but looking at DNA methylation as a possible factor in carcinogenesis would have allows some more balance instead of looking at its therapeutic benefits. The therapeutic benefits are importance and add the “so what” to the investigation of DNA methylation and CRC, however more balance is expected in a review paper to look at all possibilities.