The Australian Centre for Functional Medicine reports on a new study explaining how the microbiota of your mouth influences oral squamous cell carcinoma. The study also reports on a way to fight off bacteria and inhibit cancer growth. Learn what Modern Functional Medicine can do to protect you from oral cancer.
Many studies have shown correlations between oral bacteria and cancer, but few have demonstrated the mechanics of such correlation: how can oral bacteria influence cancer growth?
Today, the Australian Centre for Functional Medicine reports on a ground-breaking new study that not only discovers the mechanisms behind bacterial-induced cancer growth but also finds a potential cure. Cancer and human-associated bacteria have a long history, as we reported in a previous article.
The new study, published today in the open-access journal PLoS Pathogens, shows how three bacteria, Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum, promote the growth of oral squamous cell carcinoma(OSCC), the most common form of oral cancer (Kamarajan 2020).
The study also shows, for the first time, that the antibacterial nisin can inhibit the growth of these bacteria and effectively fight–off cancer growth. Nisin is an anti-bacterial chemical produced by the bacteria from the Lactococcus and Streptococcus genera, and it is commonly used as a food preservative.
The findings give hope for the development of a new and effective treatment for oral cancer and opens the door for further research elucidating the role of bacteria in cancer growth and treatment. According to the authors, their findings could “advance treatment for oral cancer and establish a novel paradigm for cancer treatment focused on antimicrobial-based therapies”.
These results show the importance of understanding the role of bacteria in cancer and other diseases. This is an approach that the Australian Centre for Functional Medicine has followed since our inception.
How bacteria promote cancer
A key finding of this study concerns how these three bacteria can promote the spread of oral squamous cell carcinoma. The study explored how T. denticola interacted with two specific cell signalling pathways called the integrin alpha V/FAK and the TLR/MyD88 signalling pathway.
At the heart of the integrin alpha V/FAK signalling pathway is the protein integrin alpha V, which is involved in fundamental cellular processes, such as cell migration and adhesion. For the TLR/MyD88 signalling pathway, a type of proteins called toll-like receptors are known for their involvement with periodontal disease and cancer pathogenesis.
Alterations to the function of integrin alpha V and toll-like receptors proteins are associated with different cancers. For example, upregulation of integrin alpha V (meaning that the protein is overproduced) is associated with prostate and colon cancer.
In this new study, researchers found that T. denticola had a direct influence in the expression of integrin alpha V. Cell-based experiments showed that when cancer cells were exposed to T. denticola, production of integrin alpha V was upregulated, meaning that higher levels of this protein were produced. The study found that these high levels of integrin alpha V proteins led to an enhanced growth of cancer cells.
The pathogens
The mouth is home to as many as 1000 different bacterial species, according to studies comparing the oral microbiota across different patients. In any one person, as many as 50 different bacterial species can normally live in the mouth. Read more about your oral microbiota in this article, where we give an overview of the microbiota across all your body.
When bacterial dysbiosis occurs, certain pathogenic bacteria can take over and cause disease. This is what happens with chronic periodontitis.
Porphyromonas gingivalis and Treponema denticola – these two bacterial species are the primary drivers for chronic periodontitis, a condition that causes inflammation of the gum, bone resorption, and can potentially lead to tooth loss. However, they are also associated with other conditions. For example, P. gingivalis has been identified as an important risk factor in the development of Aβ plaques, dementia, and Alzheimer’s disease (AD) (Dominy 2019). This pathogenic bacterium has also been found to affect the gut immune system and the gut microbiota composition, according to one recent study based on mice (Sato 2017).
Fusobacterium nucleatum – this bacterium is not a pathogenic species under normal oral conditions. F. nucleatum is a commensal oral bacterium, which means it is part of the normal oral flora. However, alterations of the normal oral microbiota, called dysbiosis, can cause an overgrowth of this bacterium, making it pathogenic. F. nucleatum is associated with a wide range of health conditions, including periodontitis, gingivitis, endodontic infections, adverse pregnancy outcomes, colorectal cancer, Inflammatory Bowel Disease, appendicitis, atherosclerosis, rheumatoid arthritis, Alzheimer’s disease and other conditions (Reviewed in Han 2015)
Are you at risk?
- gingivalis, F. nucleatum and T. denticola are commonly found in people with gingival or periodontal infections. However, a study has shown that as many as 25% of healthy people can carry P. gingivalis in their mouths (Griffen 1998). According to a recent report from the Australian Dental Association, periodontitis affects around 7% of Australian adults, but the risk increases with age. According to the report nearly 40% of all Australians over 55 years of age experience some degree of periodontitis. The condition is also associated with certain risk factors, like smoking, diabetes and obesity.
Modern Functional Medicine and Oral Cancer
At the Australian Centre for Functional Medicine, we keep track of research development on a wide range of health topics, including the role of microbes in health. In line with the findings of this new study, linking oral bacteria and cancer, our modern approach to functional medicine is focused on understanding the role of microbes in human health. At the heart of our approach to health, is our goal to test for microbial dysbiosis in the mouth or in other parts of the body, like the skin, gut, and any other part of the body that harbours a microbiota. Read more about microbes and health on our website.
At the Australian Centre for Functional Medicine, we perform comprehensive microbiome testing on our patients, with the goal of identifying instances of dysbiosis and microbial overgrowth. Patients at our clinic who have a confirmed case of dysbiosis are treated with a combination of anti-microbial treatments and probiotic therapies, which are guaranteed to eliminate the disease-causing pathogens and improve the diversity and richness of commensal, beneficial microbiota.
References
- Kamarajan P, Ateia I, Shin JM, Fenno JC, Le C, Zhan L, et al. (2020) Periodontal pathogens promote cancer aggressivity via TLR/MyD88 triggered activation of Integrin/FAK signaling that is therapeutically reversible by a probiotic bacteriocin. PLoS Pathog 16(10): e1008881 Read it!
- Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, Nguyen M, Haditsch U, Raha D, Griffin C, Holsinger LJ. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science advances. 2019 Jan 1;5(1):eaau3333. Read it!
- Sato K, Takahashi N, Kato T, Matsuda Y, Yokoji M, Yamada M, Nakajima T, Kondo N, Endo N, Yamamoto R, Noiri Y. Aggravation of collagen-induced arthritis by orally administered Porphyromonas gingivalis through modulation of the gut microbiota and gut immune system. Scientific reports. 2017 Jul 31;7(1):1-3. Read it!
- Griffen AL, Becker MR, Lyons SR, Moeschberger ML, Leys EJ. Prevalence of Porphyromonas gingivalisand periodontal health status. Journal of clinical microbiology. 1998 Nov 1;36(11):3239-42. Read it!
- Rafiei M, Kiani F, Sayehmiri K, Sayehmiri F, Tavirani M, Dousti M, Sheikhi A. Prevalence of anaerobic bacteria (P. gingivalis) as major microbial agent in the incidence periodontal diseases by meta-analysis. Journal of Dentistry. 2018 Sep;19(3):232. Read it!
- Han YW. Fusobacterium nucleatum: a commensal-turned pathogen. Current opinion in microbiology. 2015 Feb 1;23:141-7. Read it!
