The Role of the Microbiome in Oral Squamous Cell Carcinoma with Insight into the Microbiome–Treatment Axis
Abstract
:1. Introduction
2. Role and Function of the Microbiome
3. Understanding the Microbiome First in Health, Then in Disease
4. Microbiome and Pathogenetic Mechanisms Underlying OSCC
5. Premalignant Lesions, the Story Before OSCC
6. Protumoural Bacterial Strains
7. Protective Bacterial Strains Against OSCC Development and Progression
8. Lactic Acid Bacteria, the Controversial Order
9. Microbiome as a Potential Diagnostic Tool
10. Effects of Smoking, Smokeless Tobacco and Alcohol on the Oral Microbiome
11. Oral Mycoplasma
12. Oral Archaea
Type of bacteria | Genera/Strains | Possible associated roles in OSCC development and/or progression |
Actinobacillus | Can upregulate the production of CCL20 in oral cancer cell lines [139] | |
Harmful-associated (pro-tumoural strains) bacteria | Aggregatibacter | Expression of proinflammatory cytokines [140] |
Capnocytophaga | May stimulate chronic inflammatory processes | |
C itrobacter | In murine models, strains of Citrobacter induce mucosal hyperplasia and inflammation [141] | |
C lostridia | Clostridial spores have been shown to have an affinity for hypoxic regions of solid tumours and may be factors in OSCC development Clostridial strains have however been used in cancer therapy [142] | |
Cutibacterium (Propionibacterium) | Induction of pro-inflammatory cytokines (IL-6 and IL-8). Strains have been associated with prostate cancer [143] | |
E nterococcus | Extracellular superoxide may produce genomic instability [144] Enterococcus strains associated with chronic inflammation and development of other cancers [145] | |
Eubacterium saburreum | Periodate-resistant antigen (PS L13) [146] may elicit immune reactions | |
Exiguobacterium oxidotolerans | High catalase activity may protect cancer cells [147] | |
Fusobacterium | Stimulation of pro-inflammatory cytokines (IL-6, IL-8) FadA adhesin of Fusobacterium nucleatum can increase transcription of Wnt, causing increased cell proliferation Fap 2 reduces immune cell activity Increases matrix metalloproteinase activity, leading to degradation of basement membrane | |
G emella | Associated with upregulation of interleukins (IL-23A) in cancer [148] | |
Johnsonella ignava | May stimulate chronic inflammatory processes | |
Leptotrichia buccalis | Contains a potent phenol-soluble lipopolysaccharide endotoxin that can stimulate inflammation [149] | |
Oribacterium | Production of acetate as a metabolic byproduct, a substrate quickly utilised by hypoxic growing OSCC tumours | |
Parvimonas | Associated with development of colorectal cancers [150] | |
Peptostreptococcus stomatitis | Has been associated with invading OSCC front | |
Porphyromonas gingivalis | Activation of complement system Pro-inflammatory cytokine release Prevents cell apoptosis (inhibition of cytochrome C, reduced caspase 3 activity and secretion of nucleoside diphosphate kinase) Further prevents apoptosis by upregulating anti-apoptotic genes BCL2 and surviving Upregulation of colon cancer-associated transcript 1 Increased enzyme production—nicotinamide N methyltransferase Gingipains activate matrix metalloproteinases Bacteria is a potent PD/1/PD- L1 activator, mediating immune bypass Induction of epithelial to mesenchymal transition FIMA adhesin molecule of bacteria affects cell cycle and alters tumour suppressor gene expression Acetaldehyde producer | |
P revotella | Increased Activation of Toll-like receptor 2 and promotion of T helper type 17 cells and associated mucosal inflammation Potent activators of pro-inflammatory mediators IL-6 and IL-8 as well as TNF-gamma [151] | |
Pseudomonas aeruginosa | Chronic inflammatory stimulation DNA cell damage May promote metastasis | |
R othia | Potent acetaldehyde producers | |
Staphylococcus aureus | Staphylococcal α-toxin can activate pro-inflammatory cytokines and activate nuclear factor-KB This bacterium has been found to be in increased abundance in squamous cell carcinoma of the skin (associated with actinic keratosis) [152] | |
Streptococcus gordonii, parasanguinis and salivarius | Streptococcal strains can produce acetaldehyde and show alcohol dehydrogenase enzyme activity [153] | |
Tannerella (forsythia) | Induces pro-inflammatory cytokine production Cysteine-like proteases may arrest cell cycle in G2 phase [154] | |
Type of bacteria | Genera/Strains | Role in OSCC prevention and/or cessation |
Protective bacteria | Streptococcus mitis | Their presence is very important in the prevention of colonisation of more virulent micro-organisms [155] |
Streptococcus gordonii | May have protective role, such that epithelial cells do not respond to Porphyromonas gingivalis-induced epithelial cell proliferation stimulation [156] | |
Streptomyces | Some species have been shown to inhibit cell growth [157], including apoptosis of cancer cell lines [158] | |
Neisseria | Can break down toxins of tobacco | |
Corynebacterium and Kingella | Can metabolise various toxic compounds by xenobiotic biodegradation | |
Veillonella | Naturally inhabits the dorsum of the tongue and thus may have more protective properties in this region [159] |
13. Oral Mycobiome
14. Viruses
14.1. Human Papilloma Virus, Epstein–Barr Virus and Herpes Simplex
14.2. The Prodigy of HIV and All Players of the Microbiome
15. The Microbiome–Treatment Axis in OSCC
16. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sami, A.; Elimairi, I.; Stanton, C.; Ross, R.P.; Ryan, C.A. The Role of the Microbiome in Oral Squamous Cell Carcinoma with Insight into the Microbiome–Treatment Axis. Int. J. Mol. Sci. 2020, 21, 8061. https://doi.org/10.3390/ijms21218061
Sami A, Elimairi I, Stanton C, Ross RP, Ryan CA. The Role of the Microbiome in Oral Squamous Cell Carcinoma with Insight into the Microbiome–Treatment Axis. International Journal of Molecular Sciences. 2020; 21(21):8061. https://doi.org/10.3390/ijms21218061
Chicago/Turabian StyleSami, Amel, Imad Elimairi, Catherine Stanton, R. Paul Ross, and C. Anthony Ryan. 2020. "The Role of the Microbiome in Oral Squamous Cell Carcinoma with Insight into the Microbiome–Treatment Axis" International Journal of Molecular Sciences 21, no. 21: 8061. https://doi.org/10.3390/ijms21218061