The Role of Oral Microbiome in Oral Cancer Development

Key Bacterial Species Associated with Oral Cancer Progression

Porphyromonas gingivalis

P. gingivalis is an anaerobic bacterium frequently associated with periodontitis and has been implicated in various cancers, including OSCC. It promotes inflammation and tissue destruction, creating a tumor-promoting microenvironment. Elevated levels of P. gingivalis have been detected in OSCC tissues, correlating with tumor aggressiveness and poor prognosis (Mivehchi et al., 2025).

Fusobacterium nucleatum

F. nucleatum is another bacterium often found in dysbiotic oral microbiomes and is linked to various cancers. It enhances the invasiveness of cancer cells by inducing epithelial-mesenchymal transition (EMT), facilitating tumor metastasis (Sun et al., 2023). F. nucleatum has been shown to activate signaling pathways that promote cancer cell survival and proliferation.

Parvimonas micra

Recent studies have demonstrated that P. micra plays a critical role in the progression of OSCC through mechanisms involving the TmpC-CKAP4 axis. The interaction between P. micra and CKAP4 in OSCC cells promotes metabolic alterations, such as enhanced glycolysis and autophagy, leading to increased tumor growth and metastasis (Qi et al., 2025).

Mechanisms Linking Oral Bacteria to Tumor Metastasis

The mechanisms by which oral bacteria contribute to tumor progression are multifaceted. Chronic inflammation induced by bacterial infections leads to the activation of various oncogenic pathways, including:

NF-κB Pathway: This pathway is activated by bacterial lipopolysaccharides (LPS) and promotes the expression of inflammatory cytokines and growth factors that facilitate tumor progression (Mivehchi et al., 2025).
HIF-1α Activation: Bacterial infections can lead to hypoxia within the tumor microenvironment, stabilizing HIF-1α and promoting glycolysis and autophagy, critical processes for tumor survival and metastasis (Qi et al., 2025).
EMT Induction: Bacterial components can modulate the expression of EMT markers, promoting the invasive characteristics of cancer cells (Sun et al., 2023).

Table 1: Mechanisms of Bacterial Influence on OSCC Pathogenesis

Mechanism	Bacterial Species	Effect on OSCC
NF-κB Activation	P. gingivalis	Promotes tumor inflammation
HIF-1α Stabilization	P. micra	Enhances glycolysis and autophagy
EMT Induction	F. nucleatum	Increases metastatic potential

Impact of Oral Infections on Cancer Treatment Outcomes

Oral infections significantly affect the efficacy of cancer treatments. The presence of specific bacteria can lead to altered drug metabolism, reduced therapeutic efficacy, and increased resistance to treatment. For instance, F. nucleatum has been shown to enhance resistance to chemotherapy by modulating the tumor microenvironment and promoting survival pathways in cancer cells (Yu et al., 2023).

Therapeutic Potential of Targeting Oral Microbiota in OSCC

Targeting the oral microbiome presents a novel approach for OSCC treatment. Strategies include:

Antibiotic Therapy: The use of specific antibiotics to reduce pathogenic bacterial populations may enhance the effectiveness of conventional cancer treatments (Mivehchi et al., 2025).
Probiotics: Introducing beneficial bacteria may help restore a healthy oral microbiome, potentially reducing inflammation and improving treatment outcomes (Mivehchi et al., 2025).
Targeting Bacterial Pathways: Developing therapeutics that inhibit the bacterial factors involved in tumor progression, such as the TmpC-CKAP4 interaction, offers a promising avenue for research (Qi et al., 2025).

Table 2: Therapeutic Strategies for Targeting Oral Microbiota

Strategy	Mechanism	Potential Outcome
Antibiotic Therapy	Reduces pathogenic bacteria	Enhances treatment efficacy
Probiotics	Restores healthy microbiome	Reduces inflammation
Targeting Bacterial Pathways	Inhibits cancer-promoting interactions	Reduces tumor growth and metastasis

FAQ

What is the role of the oral microbiome in cancer development?

The oral microbiome can influence cancer development by promoting chronic inflammation, altering immune responses, and producing oncogenic metabolites.

Which bacteria are most commonly associated with oral cancer?

Key bacteria include Porphyromonas gingivalis, Fusobacterium nucleatum, and Parvimonas micra, all of which have been linked to increased tumor progression and metastasis.

How do oral infections affect cancer treatment?

Oral infections can alter drug metabolism, reduce the efficacy of cancer treatments, and increase resistance to therapies, complicating treatment outcomes.

What therapeutic strategies are available for targeting the oral microbiome in cancer treatment?

Strategies include antibiotic therapy to reduce pathogenic bacteria, probiotics to restore healthy microbiota, and developing drugs that inhibit bacterial factors involved in cancer progression.

References

Mivehchi, H., Eskandari-Yaghbast, A., Pour Bahrami, P., Elhami, A., Faghihinia, F., Nejati, S. T., Kazemi, K. S., & Nabi Afjadi, M. (2025). Exploring the role of oral bacteria in oral cancer: a narrative review. Discover Oncology, 27(1), 2. https://doi.org/10.1007/s12672-025-01998-2
Qi, H., Gao, H., Li, M., Sun, T., Gu, X., Wei, L., Zhi, M., & Feng, Q. (2025). Parvimonas micra promotes oral squamous cell carcinoma metastasis through TmpC-CKAP4 axis. Nature Communications, 14(1), 1-15. https://doi.org/10.1038/s41467-025-57530-1
Sun, J., et al. (2023). F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production. EBioMedicine, 88, 104444. https://doi.org/10.1016/j.ebiom.2023.104444
Yu, T., et al. (2023). Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell, 170(5), 548-563.e516. https://doi.org/10.1016/j.cell.2017.07.008