Study Finds Gum Disease Bacteria Related To Colon Cancer

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States, according to the Centers for Disease Control and Prevention (CDC), whose US Cancer Statistics Working Group reported in 2012 that 134,784 people in the United States were diagnosed with CRC, including 70,204 men and 64,580 women, AND that 51,516 people in the United States died from CRC, including 26,866 men and 24,650 women.¹

Even with improved detection…CRC can still be deadly

According to the American Cancer Society, in 2015 this type of cancer is expected to be responsible for about 47,700 deaths — or 131 people per day. While the death rate has been dropping in the last 20 years thanks to better screening, and earlier, better treatment, it is still a deadly diagnosis.²

There are a number of well-known risk factors for CRC, which are listed on a variety of cancer information websites. In general, CRC is thought to result from a combination of genetic and epigenetic factors and diet. However, research is showing that there is one other important factor that should also be considered – your oral health, and whether or not you have periodontal disease and specific bacteria associated with it.

Gum disease bacteria related to colon cancer?

Up until very recently, no one had ever thought to consider studying the various strains of bacteria that are located in the mouth, and look at the implications of where they may also be found in the rest of the body. When one of these, Fusobacterium nucleatum, ends up in the colon — recent research is suggesting it’s a possible cause of CRC.

Dr. Yiping Han, PhD is currently Professor of Microbial Sciences in Dental Medicine and Microbiology & Immunology at Columbia University College of Dental Medicine in New York, NY, and specializes in periodontal disease, the human microbiome, and oral-systemic connections. Over the past decade, Dr. Han and her team at Case Western Reserve University’s School of Dental Medicine had done extensive research on a specific type of bacteria that’s found in nearly everyone’s mouth, Fusobacterium nucleatum.

Over a period of more than a decade prior to the discovery of the CRC connection (2012),³ Dr. Han and her teams have not only led the research into F. nucleatum‘s interactions with periodontal and extraoral cells,^4-6 but have also connected this bacterial species to preterm birth, stillbirth and death of newborn animals.^{7, 8}.

In recent research, they also confirmed specific features of how F. nucleatum — which is directly associated with periodontitis (gum) disease – is also associated with colon cancer.⁹ While exactly how F. nucleatum interacts with normal colon cells — and exactly how that may lead to CRC – is as yet unknown, the study showed a direct and specific association between the two.

F. nucleatum is coated with a unique, adhesive-like substance, FadA, which causes the bacteria to stick to a specific type of receptor on various cells — including normal colon cells — allowing it to invade those cells. This causes inflammation, which can then lead to the cells becoming cancerous, resulting in CRC. Importantly, inflammation is a common denominator in diverse disease processes that often span multiple body systems.⁹

This all-too-common denominator of inflammation has been identified by yet another team of researchers at Harvard Medical School and the Harvard School of Public Health in connection with F. nucleatum and bacteria like it—by recruiting cells from the patient’s own immune system and using their tumor-infiltrating properties to promote CRC development¹⁰—read the summary abstract from Cancer Discovery here (which also discusses Dr. Han’s work with fadA):

http://cancerdiscovery.aacrjournals.org/content/early/2013/10/08/2159-8290.CD-NB2013-145.full

Analysis of the FadA within F. nucleatum shows that it its gene expression levels are 10 to 100 times higher in patients with pre-cancerous and cancerous tumors, as compared to normal individuals. This discovery opens the door for more research into the workings of FadA.⁹

Results from other researchers have also identified significantly increased amounts of F. nucleatum DNA in CRC-positive biopsy specimens, versus those from normal colon tissue, AND significantly increased F. nucleatum DNA in high-grade pre-cancerous colon tissue.¹¹ Both this team¹¹ and another team¹² also found lower levels of F. nucleatum to be associated with longer cancer survival times in CRC patients.

Further research and testing will probably result in new diagnostic tools, not only for colon cancer, but also for other areas (including other cancers) where F. nucleatum has been associated with adverse outcomes.

Unfortunately, nearly all of us have F. nucleatum in our mouths – including the FadA that’s part of it. That’s why you, your doctor and your dentist should be talking about this nasty bug.

There’s even a salivary DNA test available right now that your dentist or periodontist can perform to tell you if you have F. nucleatum. Check out the Oral DNA Labs website for further info:

http://www.oraldna.com/pdf/OralDNALabs-MyPerioPath-report.pdf

You can’t order the test online, but you can print out a .pdf of a sample MyPerioPath® test panel (which shows F. nucleatum as part of the test), take it to your hygienist, dentist or periodontist, discuss it, and ask to have the test done.

With enough of these conversations, further research into isolating the FadA factor will ultimately lead to ways to neutralize or eliminate it from the mouth — preventing these problems in the first place. Identification of the FadA portion of F. nucleatum could also be used to develop diagnostic tools for earlier identification of CRC in those who are most at risk.

In 2010 Dr. Han published a paper on the first documented case of a human term stillbirth caused by F. nucleatum, which was isolated from the placenta and fetus—AND in plaque below the gumline in the mother’s mouth.⁸

So, until our understanding of this bug’s threats to your health–and your baby’s–improves, treating periodontal disease, especially for those who are at high risk for CRC, or are pregnant or planning to become pregnant, is something you should discuss with your physician, hygienist and dentist.

Stay tuned for my upcoming post on oral bacteria and pregnancy–and why a healthy mouth is a prerequisite for having a healthy baby!

 

REFERENCES

 

1. CentersforDiseaseControlandPrevention. Colorectal Cancer Statistics. Atlanta: CDC; 2015 [cited 2015 September 29]; Available from: http://www.cdc.gov/cancer/colorectal/statistics/index.htm.
2. Society AC. 2015 [cited 2015 September 29]; Available from: http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-key-statistics.
3. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012 Feb;22(2):299-306.
4. Han YW, Shi W, Huang GT, Kinder Haake S, Park NH, Kuramitsu H, et al. Interactions between periodontal bacteria and human oral epithelial cells: Fusobacterium nucleatum adheres to and invades epithelial cells. Infect Immun. 2000 Jun;68(6):3140-6.
5. Han YW. Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol. 2015 Feb;23:141-7.
6. Han YW, Wang X. Mobile microbiome: oral bacteria in extra-oral infections and inflammation. J Dent Res. 2013 Jun;92(6):485-91.
7. Han YW, Redline RW, Li M, Yin L, Hill GB, McCormick TS. Fusobacterium nucleatum induces premature and term stillbirths in pregnant mice: implication of oral bacteria in preterm birth. Infect Immun. 2004 Apr;72(4):2272-9.
8. Han YW, Fardini Y, Chen C, Iacampo KG, Peraino VA, Shamonki JM, et al. Term stillbirth caused by oral Fusobacterium nucleatum. Obstet Gynecol. 2010 Feb;115(2 Pt 2):442-5.
9. Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe. 2013 Aug 14;14(2):195-206.
10. Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013 Aug 14;14(2):207-15.
11. Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T, Liska V, et al. Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis. 2014 Aug;33(8):1381-90.
12. Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y, Nowak JA, et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. 2015 Aug 26.