How Colorectal Cancer is Affected by the Microbiome

colorectal cancer

That dreaded time is coming up. You SO don’t want to do this.

WHY IS THIS EVEN NECESSARY?

You need to see your doctor to get that awful test done.

It’s so uncomfortable.

Why do you have to go?

No family history, no personal history, not having any problems.

Do you really need to go?

It’s time for your colonoscopy to check for colorectal cancer.

With last month being March, colorectal cancer awareness month, we wanted to share some information with you on exactly why it’s so crucial to get this test done regularly — and how the microbiome can affect your chances of getting this terrible disease.

What is Colorectal Cancer?



 

Colorectal cancer (CRC) is the 3rd most common cancer in the United States in both men and women.

Most think that it is more common in men, but actually, there is an equal for both genders to get CRC.

CRC is found in either the colon or rectum.

It is called colorectal cancer since both the colon and rectum make up the large intestine and both present in a similar fashion.

The large intestine mostly consists of the colon. Different parts of the colon include:

  • Ascending colon- right side going from bottom to top of the abdomen
  • Transverse colon- going across the top of your abdomen from right to left
  • Descending colon- going from the top of the left abdomen to the bottom
  • Sigmoid colon- the “s” shaped part of your colon that joins the rectum

The proximal colon is made up of the ascending and transverse colons, while the distal colon consists of the descending and sigmoid colons.

Colorectal Polyps

CRC often starts with a polyp in the lining of either the colon or rectum. Colon cancer is completely preventable if the polyps are found early.

There are two different classes of polyps: adenomatous and hyperplastic/inflammatory.

Adenomas can be pre-cancerous or cancerous. Hyperplastic polyps are typically not pre-cancerous.

When a polyp is found there are a few different things that may make your doctor think they can be cancerous.

These include:

  • Size- larger than 1 cm
  • Quantity- 2 or more
  • Dysplasia- a pre-cancer condition where cells found are abnormal but not quite cancerous

CRC polyps can spread cancer to other places in the body by attaching to and growing into the colon or rectal walls.

Once they grow in deeper, they affect the blood and lymph vessels where the cancerous tissues can be circulated throughout the body.

There are different outcomes between left and right tumors. Right-sided colorectal tumors are found to come from the midgut.

The midgut includes the ascending colon, cecum, and first ⅔ of the transverse colon.

Left-sided colorectal tumors are found to come from the hindgut.

The hindgut consists of the last third of the transverse colon, splenic flexure, descending colon, sigmoid colon, and rectum.

Since each part of the gastrointestinal tract — including the large intestines — contains different bacteria, it will cause differences in tumor growth and prognosis.

Gut Bacteria and Colorectal Cancer

Colorectal Cancer

Higher class societies are having higher and higher numbers of CRC cases.

There are numerous reports on how diet and CRC have a high correlation. Research was done to see how the environment affects the chances for people to get CRC.

African Americans and rural South Africans were tested in a diet swap.

For two weeks each consumed the typical diet of the other.

African Americans are used to consuming a Western diet and have a much higher rate of CRC at approximately 65 out of 100,000.

South Africans typically consume a diet high in fiber and low in fat and have a rate of less than 5 out of 100,000 people with CRC on average.

African Americans were given a diet low in fat and high in fiber while the South Africans were given a diet high in fat and low in fiber.

After two weeks the mucosal biomarkers were retested.

It was found that not only the diets were swapped but also the chances of contracting CRC.

Bacteria B. fragilis was significantly higher in South Africans after the study. This is a good indicator that the microbiome does have an important role in CRC.

Along with B. fragilis, there are a few other gut bacteria that have been linked to CRC.

Bacteria Connected to CRC

Sulfidogenic bacteria are the main type of bacteria currently known to be connected to CRC.

Sulfidogenic bacteria produce hydrogen sulfide. Hydrogen sulfide negatively impacts DNA since it is a genotoxic compound.

It is believed — but needs to be further investigated — that hydrogen sulfide affects the functionality of the mitochondria when it is diffused into the epithelial cells.

This is how the DNA becomes affected and mutates to become cancerous.

1. Bacteroides fragilis (B. fragilis)

  • fragilis has two subtypes: nontoxigenic and enterotoxigenic.

Enterotoxigenic Bacteroides fragilis has been found to be a strong influence in the development of CRC.

  • fragilis toxin (BFT) is created by ETBF. BFT has been noticed in diarrhea, inflammatory bowel disease, and CRC.

BFT is encoded by the bft gene. It was found that all late stage cancers are positive of the bft gene. Stages I & II of CRC were found significantly less at 72.7% positivity of the bft gene.

2. Streptococcus bovis (S. bovis)

  1. bovis was actually one of the first bacteria found to be linked to CRC back in 1966.

Patients suffering from S. bovis related bacteremia — otherwise known as bacteria in your blood — don’t always necessarily get CRC.

The ranges are anywhere from 6-71% across different studies.

However, Streptococcus gallolyticus (S. gallolyticus) — a subtype of S. bovis — increases those percentages to 33-71%.

DNA from S. gallolyticus was found in 71% of cancer patients in one study, as opposed to 8% in healthy tissues.

Along with CRC, S. gallolyticus also has been noticed with endocarditis cases. 94% of patients with S. gallolyticus related bacteremia also suffer from endocarditis.

Only 18% of CRC patients end up with endocarditis when infected with other S. bovis bacteremia cases.

3. Fusobacterium nucleatum (F. nucleatum)

CRC patients tend to have higher concentrations of F. nucleatum in fecal samples and lower microbial diversity.

  • nucleatum is found more frequently in patients that have proximal CRC as opposed to those with distal CRC.

Fusobacterium types are part of the sulfidogenic bacteria group. F. nucleatum releases hydrogen sulfide.

Both IL-10 and TNF-α are inflammatory cytokines messaging cells — and are increased with the presence of F. nucleatum.

  • nucleatum is typically found in oral diseases like gingivitis and periodontal disease. Studies are currently going on to see the correlation between this particular oral bacteria and how it travels to the colon.

4. Clostridium septicum (C. septicum)

  • septicum is a special — but very dangerous — bacteria that is typically found within the gastrointestinal (GI) tract.

57% of malignant tumors related to C. septicum originate in the cecum. The highly acidic environment of the GI tract — especially the cecum —  is the perfect place for C. septicum to begin and maintain its growth.

When there is colorectal inflammation there can be ulcerations that lead to bacteremia and gas gangrene — AKA myonecrosis. Myonecrosis has a mortality rate of 79% within the first 48 hours.

  • septicum is not found to be a cause of CRC, however, it is found to affect already beginning tumors and create the perfect storm for them to become cancerous.

How Can You Protect Your Microbiome From Developing Colorectal Cancer

Microbiome

1. Diet

2. Diet

3. Diet

Your diet has been shown — in numerous ways — to affect your microbiome and entire body tremendously.

Keeping a high fiber and low-fat diet will keep your bacteria happy and healthy and help to prevent dangerous diseases like CRC.

For some other tips on how to prevent CRC, check out our other article on how to prevent colon cancer.

It may be your least favorite thing to go and get colonoscopies, but it is painless and so worth it to know you aren’t suffering from these bacterial terrorists.

It is recommended to start getting them between 45-50, but there is evidence that younger people are now starting to get CRC.

If you have a family history of CRC you should talk with your doctor about when to start getting screenings.

If you found this article helpful in understanding the bacteria behind CRC give it a “Share” or comment and let us know what you think!