Exploring the link between the oral microbe Porphyromonas gingivalis and pancreatic cancer

Porphyromonas gingivalis is a member of the dysbiotic oral microbiome associated with oral inflammation. Intriguingly, multiple epidemiological studies link P. gingivalis to an increased risk of pancreatic cancer. Given that oral bacteria are detected in PDAC, and both mouse and human pancreata harbor microbiota, we tested the ability of P. gingivalis to migrate from the oral cavity to the pancreas, and explored the involvement of P. gingivalis in pancreatic tumorigenesis using cell lines and a xenograft model. P. gingivalis was detected in the mouse pancreas following oral inoculation. In vitro, P. gingivalis induced proliferation of pancreatic cancer cells, however, surprisingly, this effect was independent of Toll-like receptor 2, the innate immune receptor engaged in response to P. gingivalis in the oral cavity. Instead, we found that P. gingivalis survives inside pancreatic cancer cells, a trait that is selectable and enhanced by hypoxia, a characteristic of pancreatic carcinoma. Intracellular P. gingivalis induces markers of cancer aggressiveness and epithelial-to-mesenchymal transformation. Increased tumor cell proliferation was related to the degree of intracellular persistence, and infection of tumor cells with P. gingivalis led to enhanced growth in vivo. To the best of our knowledge, this study is the first to demonstrate migration of P. gingivalis to the pancreas, and the direct effect of exposure to P. gingivalis on pancreatic tumor progression. Our findings shed light on potential mechanisms underlying the PDAC-periodontitis link, and may lead to better diagnosis and care.