Ligature-Induced Periodontitis Drives Colorectal Cancer: An Experimental Model in Mice.

Area of Science:

• Oral Health and Disease
• Oncology
• Microbiology

Background:

• Periodontitis is a common oral inflammatory condition linked to increased colorectal cancer (CRC) risk.
• Experimental models are crucial for understanding the mechanisms connecting periodontitis and CRC.
• The specific impact of ligature-induced periodontitis on CRC development requires further investigation.

Purpose of the Study:

• To investigate the role of experimental periodontitis, induced by silk ligation, in promoting colorectal cancer.
• To analyze the effects of periodontitis on oral and gut microbiota composition.
• To explore the impact of periodontitis on the tumor immune microenvironment.

Main Methods:

• Utilized ligature-induced experimental periodontitis in murine models of colitis-associated CRC and spontaneous CRC.
• Analyzed oral and gut microbial communities using 16S ribosomal RNA gene sequencing.
• Assessed tumor progression, immune cell infiltration (PD-1+ CD8+ T cells, INF-γ+ CD8+ T cells), and microbiota transplantation.

Main Results:

• Ligature-induced periodontitis significantly promoted colorectal cancer growth, evidenced by increased tumor number, size, and load.
• Experimental periodontitis induced significant alterations in both oral and gut microbial communities.
• Periodontitis led to increased programmed death 1 (PD-1)-positive CD8+ T-cell infiltration in tumors and suppressed INF-γ+ CD8+ T-cell infiltration in a microbiota transplantation model.

Conclusions:

• Experimental periodontitis, specifically when induced by silk ligation, promotes colorectal cancer development.
• Microbiota remodeling in both the oral cavity and gut plays a key role in periodontitis-associated CRC promotion.
• Periodontitis may promote CRC by suppressing crucial anti-tumor immune responses.