How Does the Microbiota Affect the Development of Colon and Rectal Cancer?

Colon and rectal, large bowel, cancers are, in both men and women, the 3rd most common cancer type. They also rank fourth among cancers causing the most deaths. Older age, inflammatory bowel disease (IBS), inherited syndromes, a family history of bowel cancer, personal polyp history, obesity, diet, environmental factors, and lifestyle habits are among factors increasing the risk of colorectal cancers . Colon and rectal cancers usually cause no early symptoms. Colonoscopy is the most effective method for early diagnosis. Everyone aged 45 or older is advised to undergo colonoscopy for early detection of colon and rectal cancers.

What Is the Relationship Between Gut Bacteria (Microbiota) and Large Bowel Cancers?

Large bowel, colon and rectal, cancers are among cancers increasing in incidence worldwide. Obesity, dietary choices, sedentary living, alcohol, smoking, and other environmental factors and lifestyle habits affect their development.

Gut microbiotais shaped by diet and lifestyle habits. Increasing evidence in recent years shows a strong relationship between gut microbiota and colon and rectal cancers.

Today, taxonomic (bacterial 16S ribosomal RNA), metagenomic (comprehensive gene sequencing analyses), and high-throughput sequencing technology allow more detailed investigation of microbiota in the human gut. Samples required for microbiome analyses can be taken from feces and from the mucosa by biopsy .

The most valuable recommendation for healthy microbiota is the diet currently proven to be the world's best eating pattern, the Mediterranean diet:

What Is Dysbiosis?

A change in normal gut microbiome composition is called dysbiosis . Our body is full of colonies of harmless bacteria, viruses, fungi, and parasites called microbiota. Environmental influences can alter one or more bacterial colonies beneficial to our health. Many studies show that bacterial dysbiosis is associated with the development in the colon and rectum of adenomas and cancer.

What Disrupts the Balance of Gut Bacteria?

Any disruption in microbiota balance can cause dysbiosis. Factors causing it include:

• a dietary change increasing protein, sugar, or food additive intake (see processed foods)
• chemicals accidentally consumed, remaining on unwashed fruit, such as pesticides and similar chemicals
• daily alcohol consumption (two or more a day)
• newly started medications
• poor oral hygiene
• high stress or anxiety
• unprotected sexual intercourse, which can expose people to harmful bacteria.

- Related topic: Probiotics – health benefits, facts, and current scientific research

Which Bacteria Are the Usual Suspects?

Among bacteria contributing to the process beginning with dysbiosis and progressing to cancer, Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli stand out.

1. Fusobecterium nucleatumis a Gram (-), anaerobic bacterium particularly common in the mouth and saliva. Alongside dental and gum infections, it has invasive and proinflammatory effects in infections outside the mouth. F. nucleatum has been found in excessive amounts in tumors and fecal samples from patients with colon and rectal cancer. Studies show F. nucleatum levels increasing alongside carcinogenesis, from healthy intestinal tissue through adenoma to large bowel cancer. F. nucleatum levels in cancer tissue have also been shown to be a prognostic indicator, affecting disease course.
2. Escherichia coliis normally found in the gut. Certain E. coli strains can trigger inflammation in the intestine. They can also produce colibactin toxin and other toxins with oncogenic, cancer-triggering potential. Levels of mucosa-associated E. coli in cancerous bowel tissue have been observed to correlate with tumor stage and prognosis.
3. Bacteroides fragilismakes up %1-2 of human microbiota. Enterotoxin-producing B. fragilis (ETBF) may contribute to inflammation-associated tumor formation in the gut, such as colitis.

Many studies show a relationship between microbiota, intestinal adenoma formation, and subsequent cancer development. Although some bacteria are described as cancer-causing, the specific bacteria responsible and possible cancer mechanisms have not yet been fully defined. More studies are needed to understand the relationship between human gut microbiota and large bowel cancer development.

- Related topic: How does diet, the eating pattern, affect tumor metabolism?

FURTHER READING...

What Microbial Mechanisms Affect Cancer Development?

The tumor-associated luminal environment, impaired barrier function, and a group of commensal bacteria involved in tumor initiation and progression are represented.

The FadA antigen of Fusobacterium nucleatum binds E-cadherin to intestinal epithelial cells (IECs) to activate β-catenin. This leads to uncontrolled cell growth, a stem cell-like state, loss of cell polarity, and possibly MSI instability . With TLR4 and MyD88 involvement, Fusobacterium nucleatum has proinflammatory effects on the tumor microenvironment . Fusobacterium nucleatum has also been shown to activate regulatory micro-RNAand thereby modulate autophagy in IECs.

E. coli strains harboring the polyketide synthase (pks) island encoding the genotoxin colibactin are frequently observed in human colorectal tumors. Alongside colibactin's genotoxic activity, cell growth is sustained by cellular senescence associated with hepatocyte growth factor (HGF) expression.

Enterotoxigenic Bacteroides fragilis (ETBF) causes inflammation and tumors in animal models. ETBF produces reactive oxygen species (ROS) and spermine oxidase (SPO), thereby triggering DNA damage. ETBF is associated with Th17 responses.

Some sulfate-reducing bacteria, such as Bilophila wadsworthia or Alistipes spp., may exert genotoxic triggering by producing hydrogen sulfide (H2S). Both strains increase inflammation in susceptible animals.