The correlation between gut microbiota imbalance and colorectal cancer.

According to a report from the American Journal of Clinical Oncology, colorectal cancer is the second leading cause of cancer death in the United States. In 2014, there were 370,000 new cases of colorectal cancer in mainland China, ranking behind lung cancer and stomach cancer. By 2018, the incidence in China (including Taiwan) had reached as high as 520,000, far surpassing stomach cancer, making it the second most common cancer overall. By 2020, the number of new cases of colorectal cancer in China exceeded 600,000 for the first time, gradually approaching lung cancer. Among all colorectal cancer patients, hereditary colorectal cancer accounts for less than 25%, while sporadic colorectal cancer accounts for over 75%. Lifestyle is considered one of the most important environmental risk factors for colorectal cancer, especially in sporadic cases.

Gut microbiota

The human gut is a nutrient-rich environment that houses up to 100 trillion microorganisms, most of which live in the colon, with a density close to 10^11 to 10^12 cells per milliliter.^[1]. Based on the relationship between gut microbiota and the human body, bacteria can be roughly divided into three categories: beneficial bacteria, harmful bacteria, and pathogenic bacteria under specific conditions.

There are many factors that lead to dysbiosis of the gut microbiota, including early use of antibiotics, immune system deficiencies, production of genotoxic substances, changes in lifestyle, and dietary structure changes. Dysbiosis has been identified as the root cause of an increasing number of medical issues, including allergies, irritable bowel syndrome, autoimmune diseases, Clostridium difficile diarrhea, inflammatory bowel disease, obesity, diabetes, and colorectal cancer.

Application of gut microbiota regulation in the treatment of colorectal cancer

1. Dietary component metabolism

A recent study showed that 38.3% of early-stage colorectal cancer patients were associated with poor dietary habits, such as low intake of whole grains and dairy products and high consumption of processed meats. Animal saturated fats can increase bile secretion, and bile acid metabolites can induce DNA oxidative damage and promote the formation of colorectal cancer. Intake of fiber and resistant starch can promote the fermentation of gut microbiota to produce short-chain fatty acids, such as butyrate and propionate. Butyrate, as an anti-inflammatory molecule, can inhibit histone deacetylation in colon-forming cells and immune cells, inducing apoptosis in colorectal cancer cell lines.^[2]. In addition, butyrate and propionate have been shown in animal models to exert effective anti-inflammatory effects by regulating colonic regulatory T cells.^[3].

2. Probiotics

Beneficial live microorganisms for humans are collectively referred to asprobiotics, with the most widely used being lactic acid bacteria, bifidobacteria, and butyrate-producing bacteria. Bultman et al.^[4]found that probiotics can stimulate the host's immune response by enhancing macrophage activity and promote the anti-tumor effects of cytokines such as tumor necrosis factor α, interleukin 12, and interferon γ. Probiotics can also intervene to improve the gut microbiota of colorectal cancer patients, help eliminate carcinogens, and improve gut permeability.^[5]. However, not all probiotic strains exhibit anti-colorectal cancer activity, and future research needs to screen effective strains and develop probiotic preparations to control and prevent the occurrence of colorectal cancer.

3. Fecal microbiota transplantation technology

About two thousand years ago, Chinese people made 'yellow soup' from the feces of healthy individuals to orally administer to patients to treat severe diarrhea. Fecal microbiota transplantation technology has shown good safety in the treatment of benign diseases, even in individuals with impaired immune function. In the efficacy of the first administration, the highest response rate was achieved through colonoscopy or enema, followed by nasogastric tube administration and oral capsules.^[6]. Due to issues such as the acquisition and preservation of fecal microbiota from healthy volunteers and how to effectively enhance anti-tumor efficacy, research on the application of this technology in colorectal cancer patients is relatively limited.

Conclusion

Dysbiosis of the gut microbiota has been confirmed to be closely related to the pathogenesis of colorectal cancer. Nowadays, there have been preliminary findings on using gut microbiota as predictive and/or prognostic markers for colorectal cancer. It is expected that in the near future, the potential of gut microbiota can be translated into real clinical applications, and we look forward to using this method to help colorectal cancer patients achieve precise medication.

[References]

[1] Perez-Chanona E, Trinchieri G. The role of microbiota in cancer therapy [J]. Curr Opin Immunol, 2016, 39(1): 75-81. Translational Medicine Journal, Vol.10 No.1, Feb 2021 ·59·

[2] Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis [J]. Immunity, 2014, 40(1): 128-139.

[3] Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis [J]. Science, 2013, 341(6145): 569-573.

[4] Bultman SJ. The microbiome and its potential as a cancer preventive intervention [J]. Semin Oncol, 2016, 43(1): 97-106.

[5] Hendler R, Zhang Y. Probiotics in the treatment of colorectal cancer [J]. Medicines (Basel), 2018, 5(3): 101.

[6] Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection [J]. Clin Infect Dis, 2011, 53(10): 994-1002.

Note: This article is for informational purposes only and should not be considered medical advice.