Gut microbiota and cancer

The influence of the human gut microbiota on health has received increasing attention in recent years. In particular, the relationship between the gut microbiota and cancer is clearly found, and changes in the structure and function of the gut microbiota are sufficient to promote metabolic syndrome, inflammation and cancer.

1. Overview of gut microbiota

Rich and diverse members of the human gut microbiota play an important role in the maintenance of human health by assisting in the breakdown of food to release nutrients inaccessible to the host; by promoting host cell differentiation, protecting the host from invasion by pathogens, inhibiting the growth of pathogenic bacteria; and by stimulating/regulating the immune system.

The composition of the gut microbiota is very diverse including: bacteria, archaea, fungi, protozoa and viruses, of which bacteria is the main component. It was found that 85% of bacteria in the digestive system are beneficial bacteria, the remaining 15% are harmful microorganisms. The imbalance of microbiological components due to disruptive factors will lead to a state of “dysbacteriosis” – a decrease in the number of beneficial microorganisms (probiotics) and the growth of pathogenic microorganisms.

2. Mechanism of causing cancer when the microbiota is disordered

Distorted microbiota is a risk factor for cancer by three mechanisms: chronic inflammation, immunoregulatory dysregulation, and carcinogenic bacterial activity.

+ Chronic inflammation: Chronic inflammation is proven to be the cause of cancer. Inflammatory cytokines directly damage DNA, abnormal DNA methylation leads to promotion of tumor formation and growth, and accelerates invasion and metastasis. Inflammatory factors can inactivate tumor suppressor genes and activate oncogenic cells.

+ Immune disorders: Disturbances of the gut microbiota trigger a number of innate and adaptive immune responses involved in tumorigenesis.

+ The metabolites of carcinogenic microorganisms: lipoteichoic acid (LTA), secondary bile acids and lipopolysaccharide have a role in carcinogenesis: increase proinflammatory factors and intestinal cell proliferation, promote DNA damage leading to malignant changes, impair intestinal barrier function and increase permeability of toxins into the blood.

When harmful bacteria overgrow, resulting in accumulation of exotoxins and endotoxins such as cytotoxic toxin and colibactin from Escherichia coli, cytolethal toxin from Shigella dysenteriae, toxin B. fragilis from B. fragilis, extracellular superoxide and hydrogen peroxide from Enterococcus faecalis,… These bacterial toxins can directly or indirectly cause DNA damage, genomic instability, tumorigenesis, and adenocarcinoma invasion.

3. Anti-cancer mechanism of gut microbiota

+ Protect the integrity of the intestinal epithelium: Probiotics such as Bifidobacterium and the Bacteroidales family S24–7 protect against colon mucus depletion thereby reducing the penetration of inflammatory and cancerous agents.

+ Bacterial short-chain fat-producing (SCFA)- regulate the epigenetic expression of many cancer-related genes through inhibition of histone deacetylase activity, which suppresses inflammation by interacting with G protein-coupled receptors (eg, GPR43, GPR109a) on the surface of colon epithelial cells. They also support intestinal immune homeostasis by modulating the function of regulatory T cells (Tregs).

Tregs play a central role in inhibiting inflammatory and allergic responses by limiting the proliferation of effector CD4+ T cells.

+ In addition, beneficial bacteria in the gut can also support cancer treatment as a therapy to prevent tumor growth, increase treatment response and reduce side effects caused by therapy.

References:

[1]    Liu et al., “Gut microbiome in gastrointestinal cancer: a friend or foe?”, Int J Biol Sci, vol. 18, p.h 10, pp. 4101–4117, June 2022, doi: 10.7150/ijbs. 69331.

[2] C. Meng, C. Bai, T. D. Brown, L. E. Hood, and Q. Tian, “Human Gut Microbiota and Gastrointestinal Cancer”, Genomics Proteomics Bioinformatics, vol 16, p.h 1, pp. 33–49, February 2018 , doi: 10.1016/j.gpb.2017.06.002.

[3] M. Song and A. T. Chan, “Environmental factors, gut microbiota, and colorectal cancer prevention”, Clin Gastroenterol Hepatol, vol. 17, p.h 2, pp. 275–289, January 2019, doi: 10.1016/j.cgh .2018.07.012.

Article source: Nutrition Research and Development Institute (https://inrd.vn/)

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