• Understanding the Gut Microbiome's Impact on Colorectal Cancer: From Development to Treatment Response
  • Elahe Roohbakhsh amoli moghadam,1 Erfan Shapourgan,2 Ali Asghar Fallah,3 Hassan Borji,4,*
    1. Department of Clinical Science,faculty of Vetrinary Medicine,Ferdowsi Universuty of Mashhad
    2. Department of medicine,Tehran University of Medical Science
    3. Department of Biology,Faculty of basic sciences,Islamic Azad University, Mashhad Branch,Iran
    4. Department of Pathobiology of Vetrinary Medicine,Ferdowsi University of Mashhad


  • Introduction: As one of the most common cancers in the world and the leading cause of cancer-related death in the world, colorectal cancer is the third most common cancer worldwide. Recent research has revealed that the gut microbiota has a significant impact on both the susceptibility to colorectal cancer (CRC) as well as the progression of the disease. Through the modulation of processes such as inflammation and DNA damage, as well as the production of metabolites that are capable of inhibiting or promoting tumor growth, this influence is attained. It has been reported that patients with CRC have dysbiosis of their gut microbiota, which is manifested by a reduction in beneficial butyrate-producing bacteria; the number of harmful opportunistic pathogens causing inflammation has increased. Metabolism is altered in CRC due to the altered production of bacterial metabolites, among them are polyamines and short-chain fatty acids. This review summarizes data on how gut microbiota influences colorectal cancer development. In addition, bacterial metabolites impact CRC development, and specific dietary factors affect the gut microbiota as well as the likelihood of developing colorectal cancer.
  • Methods: Four global databases (PubMed, Web of Science, Scopus, and Google Scholar) were searched. The search process was accomplished using keywords such as “colorectal cancer”, “gut microbiota”, “bacterial metabolites” and ” dietary mediators”, and 750 studies were funded. After removing duplicates and excluding ineligible reports, 100 articles were eligible to be included in this systematic review. Forty-four relevant articles with complete abstracts were included in the study.
  • Results: Research suggests that the gut microbiota might play a substantial role in colorectal cancer development by generating metabolites that interact with the immune system and release genotoxic(factor of virulence). Research has shown that colorectal cancer patients have a reduced diversity of microorganisms and reduced bacterial richness in fecal samples and intestinal mucosa compared to their healthy counterparts. Moreover, colorectal cancer patients exhibit notable differences in distinct groups of bacteria, potentially influencing mucosal immunity. The prevalence of Streptococcus gallolyticus, Escherichia coli, Peptostreptococus, Shigella, Enterococcaceae or Campylobacter, Enterococus faecalis, Fusobacterium nucleatum, Enterococcaceae or Campylobacter, and Bacteroides fragilis in CRC patients is particularly high, while the prevalence of Clostridium, Roseburia, Faecalibacterium, Blautia, and Bifidobacterium decreases as well. The decline in bacteria that produce Butyrate can result in an increased number of pro-inflammatory opportunistic pathogens and imbalanced intestinal homeostasis (dysbiosis), leading to tumor formation. It has been shown that SCFAs (especially butyrate) Keep the intestinal barrier intact in colon cancer by regulating the immune response. The large intestinal fermentation of soluble fiber into SCFAs has been demonstrated to have anti-carcinogenic effects in colon cancer models in vivo. The consumption of high fiber can promote the growth of gut bacteria that produce butyrate. The addition of PUFAs, polyphenols, and probiotics to a primary prevention program may also be helpful in reducing the risk of CRC. Aside from enhancing treatment response and minimizing toxicity, intestinal microbiota can assist in cancer treatment. In the absence of dietary PUFA, polyphenols, and probiotics, fiber intake promotes butyrate-producing bacteria, which may reduce CRC risks. Adjuvants that improve and alleviate the toxicity of conventional CRC treatments can be derived from intestinal microbiota.
  • Conclusion: Colorectal carcinogenesis may be impacted by dysbiosis of the gut microbiota in several ways. By disrupting cell cycle regulation, synthesizing genotoxins, and generating harmful metabolites, pathogenic bacteria compromise the integrity of the intestinal epithelial barrier. It is also possible that some lysogenic bacteriophages found in the gut microbiota would indirectly contribute to tumor progression through bacterial lysis in the colon by affecting the bacterial population there. The gut mycobiota may also play a role in colorectal cancer development, as ecological analyses have revealed synergistic interactions among fungi, as well as antagonistic interactions between bacteria and fungi.
  • Keywords: colorectal cancer,gut microbiota,bacterial metabolites,dietary mediators