Oral Micro-Biome and Their Role in Developing Oral Cancer

Khan Z, Khan A and Malik K

Published on: 2024-11-23

Abstract

Cancer is the most notorious and devastating disease of the mankind. In most of the cases it doesn't show any symptoms until it reaches to the chronic stage that might be fatal in most of the obvious cases. Researches are being done to show the relationship between the causative agent and the diseases. There is an obvious relationship between the micro-biome and the occurrence of cancer. The most commonly studied micro-biome is the oral micro-biome. The balance in the micro-biome is important. Sometimes the balance is disturbed due to many reasons like environmental factors, poor hygienic conditions, chronic Inflammation and many more conditions. In case of oral micro-biome Dysbiosis the result is the oral cancer commonly known as Oral Squamous Cell Carcinoma. It is the multi-factorial and thus has many causes but we will here only discuss the imbalance in the oral micro-biome and its effect on OSCC.

Keywords

Dysbiosis; Micro-biome; Oral squamous cell carcinoma; Cell invasion and proliferation

Introduction

Timeline of Micro-Biome Research

The study of microorganism started with the discovery microscope by the Leeuwenhoek and thus cultivation and starting techniques were developed in 1800 and advances in this field were done with the developing of genome sequencing in 1900. In 1900 human genome project was launched and then Human Micro-biome Project was launched in 2008. In 2010 the Human Oral Micro-biome Project was launched and increase our understanding of the oral micro-biome its up-regulation factors and down regulation aspects [1,2].

Human Oral Micro-Biome Database

It enlist the microorganisms based on the 16sRNA sequencing and thus gives us the information about the cultured and the recently discovered microorganism so we can best known about the strain that cause more disturbance when it comes to the oral cancer [3,4].

Dysbiosis

Maintaining the casual balance between the microorganisms is most important mainly in the development of the immunity which is the major barrier in preventing the effects of the hazardous disease like cancer [5]. One should best make check of the proper oral hygiene first of all as healthy gut leads to the healthy body and thus leads us in developing the good immunity against the notorious diseases [6].

Oral Squamous Cell Carcinoma

It is a type of cancer that affects mucosal lining of buccal cavity, cheeks, inner lining of the lips, upper third part of tongue, gums and the underlying bones, hard palate (that form roof of the tongue), retro molar trigon (the area below the wisdom teeth) [7].

Symptoms

It may include sores or blisters that might heal in few days

Redness in mouth
Loose teeth
White patches around gum area
Pain associated with gums,teeth ,ears and jawline.
Difficulty in chewing and swallowing food
Coughing up blood
Bad breadth

Etio-Pathogenesis Of Oral Cancer

It is a multiple step phenomenon like viral carriage of a person, immunity, environment in which individual lives, medication that might develop the resistance by overuse, in female most common are the hormonal changes that might be due to pregnancy, menopause and some related phenomenon [8]. Immune system gets weak essentially after transplant surgeries like in renal and bone marrow transplant surgeries .Person own microbiota composition may play profound role in developing cancer [9].

Virus Carriage

This phenomenon can increase the risk of oral cancer by three basic steps

Insertional Mutagenesis

It is the process by which virus injects its DNA in the host cell leading to the mutation and cancer development.

Chronic Inflammation

Immune Suppression

Apart from this Kaposi sacrcoma is also associated with these factors.

Oral Bacteria and Oral Carcinogenesis

Oral Bacteria and Oral Carcinogenesis

Chronic Inflammation

It is the first step that might lead to the further cancer prognosis. This inflammation lasts much longer leads from months to years and results in mutation in the cells at genetic and epigenetic level [10]. There are more than 20 known causes of chronic inflammation that might finally lead to the development of cancer. Although inflammation is not only associated with cancer but also with autoimmune diseases like rheumatoid arthritis, lupus and neurodegenerative diseases like Alzheimer's [11]. Cardiovascular disease like stroke and high blood pressure and oral diseases like gingivitis and periodontitis.

Cell proliferation

It is the normal process that leads to cell growth, cell elongation and finally to the cell division that is controlled by the apoptosis and the associated phenomenon but sometimes pathological proliferation that may occur due to the mutation, environmental factors and by Dysbiosis takes place that results in cancer and tumour but physiological proliferation is involved in repair of injury and growth processes. Studies suggest the proliferation of pancreatic bacteria may result in development of oral carcinoma [12,13]. Metabolism of potentially carcinogenic substances Oral microbiota plays a crucial role in the metabolism of potentially pathogenic substances like they can convert nitrates to the nitrosamine which is carcinogenic. In the case the person consuming the alcohol these bacteria can convert it into acetaldehyde which is also carcinogenic. In the cigarette smokers micro biome convert nicotine of tobacco into carcinogenic compound. In people consuming a lot of meat these micro biome convert it into amine which is also carcinogenic [14].

Inhibition of Apoptosis

Actually it is natural phenomenon but when it is inhibited then cell may grow up to tumour and leads to mutagenesis. Microbiota do it by releasing the cytokines and growth factors. They also block tumour necrotic factor alpha and trail-pathway. They prevent immune mediated apoptosis of tumour cells [15].

Promotion of Cellular Invasion

Oral microbiota results in cellular invasion by destruction of extra cellular matrix and cause adhesion by integrin and cadherin, induction of epithelial to mesenchymal transition, creation of micro-environment that foster the release of chemokines and cytokines and release of metalloproteinase that degrade matrix and causes the invasion of tumour cells [16].

Role of Oral Fungi in Oral Carcinogenesis

Fungi are not primary pathogens of human race they only cause diseases in the human under the circumstances when the body immunity is weak due to some conditions like organ transplant or immunosuppression medicines that weakens the immune system making it venerable for diseases so they are secondary pathogens [17].

Candida Albicans

Candida albicans is the most common specie that is associated with oral cancer. It causes the disruption of mucosal barrier by the release of chemical toxins like acetaldehyde and nitrosamine. These chemicals result in pathogenesis by the production of biofilms, tissue inflammation and invasion. Apart from this this fungi also secrete enzymes that lead to the development of oral cancer [18,19].

Opportunistic Fungi

These fungi normally don't cause any disease because they are not able to hijack the immune system. But when the immunity is weak due to the viral disease like AIDS and when suffering from diabetes. These group of fungi then results in colonizing themselves in the oral cavity and result in the formation of resistant biofilm along with bacteria and then they also secrete the mycotoxins that finally ends in developing the cancer. These might be detected by fungi profiling which helps in developing the novel therapeutic strategies [20].

Role of Viruses in Oral Carcinogenesis

There are many viruses that have a lot of contributions in developing the oral cancer. Most common among them are herpes simplex virus, human papilloma virus, hepatitis C virus, retro virus, human T Lymphocyte virus and recently discovered Merkel cell polyomavirus [21].

Herpes Simplex Virus

There is a strong evidence of the role of herpes simplex virus-1 in the development of oral cancer. It is estimated that 80 out of 100 people suffer from this virus in their lifetime. The viral proteins have been found in oral cancer

Patients. Although the cancer is multi-factorial and causes the alterations from genetic to epigenetic level. The viral genes of herpes simplex virus causes the change in normal cellular process that lead to uncontrollable cell division and cell proliferation [22].

Human Papilloma Virus

There are more this 40 different viruses in this family that causes the tonsillitis (the inflammation of para-tonsils gland located at the back of the mouth). The most common is the HPV16 that causes the sores, redness, inflammation and finally results in physical change in the cell. When the immune system is unable to tackle these changes then result in tumour leading to the oral cancer. One of the best way to overcome the effect of this virus is by being vaccinating one-selves and avoiding the oral sex with the person who is already suffering with it and following the good hygienic conditions [23-35].

Study of Inter-Specific and Intra-Specific Variations in Salivary Micro-Biome

There is great variation in the micro-biome within and among the different species that may be because of environmental conditions, lifestyle, phenotypic effect and mutations. The interaction between the host and micro-biome also results in shaping the microbiota and sometimes pH may also influence it. Adequate methodological procedures must be applied in taking the sample and in sequencing microbiota of individual [35-45].

Changes in Abundance of Oral Micro-Biome Associated With Oral Cancer

These may include:

Firmicutes and Actinobacteria

Decreased abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) in oral cancer samples.

Fusobacteria

Increased abundance of Fusobacteria in oral cancer samples.

Bacteroidetes

Increased abundance of Bacteroidetes (especially Prevotella) in oral cancer and pre-cancer samples. Rothia in oral cancer and pre-cancer samples.

These changes in abundance may be associated with the development and progression of oral cancer.

Streptococcus and Rothia

Decreased abundance of Streptococcus and Rothia.

Using Oral Micro-Biome Profiles Methodology

This approach has been used to develop personalized medication by determining the individual micro-biome.To know the bacterial communities involved in cancer [46-51]. Impact of lifestyle on microbiota and how microbiota impacts the progress of oral cancer. To identify biomarkers for early diagnosis and prognosis. Development of techniques for early diagnosis of cancer and new therapeutic approaches to treat cancer. Most common techniques involve

16srRNA method
Proteonomics
Meta genomics
Bio-informatics and statistical analysis
Culturomics
Shot gun meta-genomics

These approaches helps in developing understanding association between microbiota and oral cancer [52].

Conclusion

This information have increased our insight about the invasion, diagnosis, prognosis of cancer and how human own micro-biota can be the reason behind the cancer. Association between the lifestyle, environment, Dysbiosis and molecular mechanisms of cancer.

Journal of Medical and Clinical Studies