Oral bacteria accelerate pancreatic cancer development in mice

Area of Science:

• Microbiology
• Oncology
• Gastroenterology

Background:

• Epidemiological studies suggest a link between pancreatic ductal adenocarcinoma (PDAC) and oral carriage of Porphyromonas gingivalis.
• Porphyromonas gingivalis is a key species associated with periodontal disease.

Purpose of the Study:

• To investigate the role of Porphyromonas gingivalis in promoting pancreatic cancer development.
• To explore the underlying mechanisms of Porphyromonas gingivalis-induced pancreatic carcinogenesis.

Main Methods:

• Tracking Porphyromonas gingivalis translocation from the oral cavity to the pancreas in a mouse model.
• Utilizing a genetically engineered mouse model (iKC mice) with inducible Kras mutation to study cooperative effects with Porphyromonas gingivalis.
• Investigating the in vitro effects of Porphyromonas gingivalis on pancreatic acinar cells and PDAC cell lines.

Main Results:

• Porphyromonas gingivalis was detected in the pancreas of mice and in human PanIN lesions.
• Repetitive administration of Porphyromonas gingivalis induced pancreatic acinar-to-ductal metaplasia (ADM) and altered the pancreatic microbiome in wild-type mice.
• Porphyromonas gingivalis accelerated PDAC progression in iKC mice and induced ADM markers in vitro, while protecting PDAC cells from nutrient stress-induced cell death.

Conclusions:

• The study demonstrates a causal role for Porphyromonas gingivalis in the development of pancreatic cancer in a mouse model.
• Findings suggest Porphyromonas gingivalis as a potential contributor to PDAC pathogenesis.