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Poor Oral Health and Oral Dysbiosis: A Link to Systemic Diseases and Cancer

Poor Oral Health and Oral Dysbiosis: A Link to Systemic Diseases and Cancer

Scientists have discovered a significant link between poor oral health and systemic diseases, including specific cancers. This connection is centered around so-called oral dysbiosis, a condition where imbalanced oral bacteria can lead to a range of health issues. It also emphasizes the crucial role of oral hygiene in promoting overall health.

The oral cavity houses more than 700 types of bacteria. While some bacterial species are beneficial for dental and overall health, in some cases, they can play a role in the development of serious systemic illnesses.

Studies show that maintaining a balanced microbial ecosystem in the mouth is crucial for oral health and it has a significant impact on how the body responds to various diseases. Dysbiosis, or an imbalanced oral microbiome, or ecosystem, can lead to various health issues ranging from common dental problems like cavities and gum disease to severe conditions such as heart disease, Alzheimer’s disease, and diabetes. [1, 2]

Recent studies have revealed that oral dysbiosis may even be involved in the development of life-threatening digestive cancers. Digestive cancers include cancers located in the esophagus, stomach, liver, pancreas, colon, and rectum. Their incidence and related mortality are increasing worldwide, with the majority of new cases of digestive cancers (63%) and related deaths (65%) occurring in Asia, followed by Europe and North America. [3].  

Scientists believe that many digestive cancer forms are influenced by various environmental factors that can be potentially changed. These include tobacco smoking, diet, alcohol consumption, and obesity. Some recent evidence also suggests a role of the human oral microbiota in the development of digestive cancers. Fusobacterium nucleatum is one bacteria species found commonly in the mouth, which is a key member of colorectal cancer-associated bacteria. However, many other oral pathogens can play a role in the development of cancer as well. [4,5]

Exposing the oral bacteria-pancreatic cancer link

One study published in the British Journal of Cancer (BJC) reported that Trepenoma denticola (Td), the bacteria responsible for periodontitis, may cause pancreatic cancer [6,7]. Pancreatic cancer is one of the deadliest forms of cancer caused by the abnormal and uncontrolled growth of cells in the pancreas – a large gland that is part of the digestive system. Around half of all new cases are diagnosed in people aged 75 or over. [8]

–  The Treponema bacterium can enter the bloodstream through inflamed gums and spread to other parts of the body. If left untreated and undiagnosed, periodontal disease contributes to the development and spread of cancer and cancer deaths – not only from oral cancer, but especially pancreatic cancer, explains Timo Sorsa, Professor of Oral and Maxillofacial Diseases at the University of Helsinki, findings of the study.

Professor Sorsa points out that Treponema bacterium shares a specific enzyme with some cancer types in the gut. This enzyme is called Treponema denticola chymotrypsin-like proteinase – or dentilisin – and it is usually found in the mouth, where it is known to contribute to severe gum disease (periodontitis). However, this same enzyme has also been observed in malignant and life-threatening tumors. [6,7].

In the oral cavity, dentilisin not only contributes to gum disease but also triggers other enzymes that promote cancer. These enzymes are called matrix metalloproteinases (MMPs), and they break down the material between cells and cell membranes, making it easier for cancer to invade healthy tissue. This connection raises concerns about potential health issues related to dentilisin in the oral cavity, Prof. Sorsa stresses.

The BJC study from 2017 was the first to show that virulence factors from gum disease bacteria could spread from the mouth to other parts of the body and take part in central mechanisms of cancer-related tissue destruction.

Since then, supplementary research has supported the study’s findings.  One report released in the International Journal of Cancer – also by Prof. Sorsa’s team – examined registry data for over 10 years on over 68,000 adults in Finland who had made a primary dental healthcare visit. This revealed that periodontitis was associated with a 33% increased risk for overall cancer mortality. The mortality risk associated with gum disease among individuals with pancreatic cancer was far higher, with a more than twofold increased risk, the study shows [7].

From fast diagnosis to a quick onset of treatment 

The links revealed so far between oral bacteria and cancer developments have inspired Prof. Sorsa’s team to search ways to help prevent cancerous developments. One potential solution is to detect gum infections in their initial stages through early diagnosis. By quickly identifying gum disease with a chair-side aMMP-8 rapid test, researchers believe that we might be able to prevent certain cancers because it allows for faster treatment of the underlying issue: gum inflammation. The test makes invisible visible, points out Prof. Sorsa. [9,10]

– Out of all MMP enzymes, especially active MMP-8 enzyme has been found to be elevated in patients suffering from gum disease leading to periodontal connective tissue destruction, Prof. Sorsa explains his team’s findings.

Periodontitis, or severe gingivitis, is a common disease that is estimated to affect as many as half of the global population – often without any symptoms at all. Early detection of these diseases is important because it allows for intervention and treatment before irreversible damage occurs. Traditional methods like check-ups and X-rays might, however, miss early signs of these diseases since they often show symptoms in later stages. Using biomarkers like aMMP-8, clinicians can spot subtle inflammation and tissue damage, allowing them to start treatment before the disease becomes visible.

–The aMMP-8 rapid test can measure and assess active periodontal adhesive tissue loss and the risk of its progression within five minutes in the dental chair non-invasively. The test complements the diagnosis, follow-up, and maintenance treatment of periodontitis and peri-implantitis, explains Prof. Sorsa. 

Advanced approaches for treating oral diseases

Periodontal and peri-implant diseases are conditions that affect the supporting structures of teeth and dental implants and can lead to tooth loss if left untreated. Gum infections can develop for various reasons. One key factor is the buildup of bacterial plaque, also known as biofilm, on the surfaces of teeth due to inadequate oral hygiene. [9]  

When discussing new treatment options and prevention of periodontitis, Prof. Sorsa emphasizes modern antibacterial methods for better oral hygiene and efficient plaque removal in periodontitis treatment and prevention. Also, research reveals that antibacterial photodynamic therapy (aPDT) is a promising approach to treat bacterial infections – even ones that do not respond well to antibiotics [12].

Lumoral treatment is the first aPDT treatment device designed for home use. It has been developed by Finnish scientists as a drug-free alternative for treating and preventing severe gum disease.

– Poor oral health is linked to over 200 chronic diseases. Lumoral is a product that enhances oral hygiene when used regularly at home, and research suggests that it can also enhance the effectiveness of professional dental care. What's more, it may reduce the need for conventional medications like antibiotics and chlorhexidine in the treatment of gum disease, according to Tommi Pätilä, a cardiac and organ transplant surgeon at the New Children's Hospital in Helsinki.

– Based on a light-activated antibacterial effect, Lumoral slows down plaque formation and significantly reduces the burden of harmful bacteria in the mouth, Pätilä explains further.

The product is suitable for patients of all ages, but it is particularly recommended for those with a history of problems with common oral diseases, tooth decay, and gum disease [9].

The crucial role of oral hygiene in cancer care

Brushing and flossing on a regular basis is key to maintaining a healthy mouth by removing dental plaque from the surfaces of teeth and interdental spaces. However, it is not always enough. Good oral hygiene requires adequate motor and mental skills. On the other hand, even when brushing teeth perfectly, studies show that even the most effective electric toothbrush only removes about 65% of harmful oral bacteria from the mouth [13].

– The key to overall well-being is good oral hygiene. For cancer patients, this is all the more important because they must maintain a high-calorie diet in order to fight the disease, notes Prof.  Dr. Tuomas Waltimo from the University of Basel.

Prof. Waltimo also acts as a private dentist at a clinic that offers dental services to patients with special dental needs, for example patients undergoing cancer treatments. He reminds that cancer treatments often bring along side-effects that can require special attention. Mucositis, as one example, can lead to generalised infection and even be life-threatening.

Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract. It can occur anywhere along the gastrointestinal (GI) tract, but oral mucositis refers to the inflammation and ulceration that occurs specifically in the mouth. Maintaining good oral hygiene habits is a prerequisite for treating oral mucositis. Lumoral supports regular mechanical dental hygiene, helps achieve gum health, and prevents inflammation when regular dental hygiene is insufficient. 

– Good oral hygiene is of paramount importance also in the management of oral mucositis. Initial findings suggest Lumoral treatment might help prevent and potentially treat oral mucositis, but this hypothesis requires further scientific research to confirm. We are, therefore, starting a new PhD study examining the topic at the University of Helsinki, Prof. Waltimo says.

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November is Stomach Cancer Awareness Month, and the goals of stomach cancer awareness primarily include: Raising public awareness and supporting educational efforts about stomach cancer, including risk factors, prevention, and early detection.

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References:

  1.   Maier, T. Oral Microbiome in Health and Disease: Maintaining a Healthy, Balanced Ecosystem and Reversing Dysbiosis. Microorganisms 2023, 11, 1453. https://doi.org/10.3390/microorganisms11061453
  2.   Silva DNdA, Casarin M, Monajemzadeh S, Bezerra BdB, Lux R and Pirih FQ (2022) The Microbiome in Periodontitis and Diabetes. Front. Oral. Health 3:859209. doi: 10.3389/froh.2022.859209
  3.     https://dceg.cancer.gov/news-events/news/2020/global-burden-gastro
  4.   Pignatelli, P.; Nuccio, F.; Piattelli, A.; Curia, M.C. The Role of Fusobacterium nucleatum in Oral and Colorectal Carcinogenesis. Microorganisms 2023, 11, 2358. https://doi.org/10.3390/microorganisms11092358
  5.   Reitano E, de'Angelis N, Gavriilidis P, Gaiani F, Memeo R, Inchingolo R, Bianchi G, de'Angelis GL, Carra MC. Oral Bacterial Microbiota in Digestive Cancer Patients: A Systematic Review. Microorganisms. 2021 Dec 14;9(12):2585. doi: 10.3390/microorganisms9122585. PMID: 34946186; PMCID: PMC8707512.
  6.   Nieminen, M., Listyarifah, D., Hagström, J. et al. Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation. Br J Cancer 118, 428–434 (2018). https://doi.org/10.1038/bjc.2017.409
  7.   Heikkilä, P., But, A., Sorsa, T. and Haukka, J. (2018), Periodontitis and cancer mortality: Register-based cohort study of 68,273 adults in 10-year follow-up. Int. J. Cancer, 142: 2244-2253. https://doi.org/10.1002/ijc.31254
  8.     https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/pancreatic-cancer/
  9.   Pakarinen, S.; Saarela, R.K.T.; Välimaa, H.; Heikkinen, A.M.; Kankuri, E.; Noponen, M.; Alapulli, H.; Tervahartiala, T.; Räisänen, I.T.; Sorsa, T.; Pätilä, T. Home-Applied Dual-Light Photodynamic Therapy in the Treatment of Stable Chronic Periodontitis (HOPE-CP)—Three-Month Interim Results. Dent. J. 2022, 10, 206. http://hdl.handle.net/10138/350606
  10. Sorsa T, Gursoy UK, Nwhator S, Hernandez M, Tervahartiala T, Leppilahti J, Gursoy M, Könönen E, Emingil G, Pussinen PJ, Mäntylä P. Analysis of matrix metalloproteinases, especially MMP-8, in gingival creviclular fluid, mouthrinse and saliva for monitoring periodontal diseases. Periodontol 2000. 2016 Feb;70(1):142-63. doi: 10.1111/prd.12101. PMID: 26662488.
  11. Sorsa T, Nwhator SO, Sakellari D, Grigoriadis A, Umeizudike KA, Brandt E, Keskin M, Tervahartiala T, Pärnänen P, Gupta S, Mohindra R, Bostanci N, Buduneli N, Räisänen IT. aMMP-8 Oral Fluid PoC Test in Relation to Oral and Systemic Diseases. Front Oral Health. 2022 Jun 10;3:897115. doi: 10.3389/froh.2022.897115. PMID: 35757444; PMCID: PMC9226345.
  12. Liu Y, Qin R, Zaat SAJ, Breukink E, Heger M. Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections. J Clin Transl Res. 2015 Dec 1;1(3):140-167. PMID: 30873451; PMCID: PMC6410618.
  13. 1 Neha Aggarwal, Sunil Gupta, Rashu Grover, Gunmeen Sadana, and Karan Bansal; Plaque Removal Efficacy of Different Toothbrushes: A Comparative Study, Int J Clin Pediatr Dent. 2019 Sep-Oct; 12(5): 385–390.  doi: 10.5005/jp-journals-10005-1669