Porphyromonas gingivalis promotes colorectal carcinoma by activating the hematopoietic NLRP3 inflammasome

Porphyromonas gingivalis (P. gingivalis) is a keystone periodontal pathogen associated with various digestive cancers. However, whether P. gingivalis can promote colorectal cancer (CRC) and the underlying mechanism associated with such promotion remain unclear. In this study, we found that P. gingivalis was enriched in human feces and tissue samples from CRC patients compared to those from colorectal adenoma patients or healthy subjects. Cohort studies demonstrated that P. gingivalis infection was associated with poor prognosis in CRC. P. gingivalis increased tumor counts and tumor volume in the ApcMin/+ mouse model and increased tumor growth in orthotopic rectal and subcutaneous carcinoma models. Furthermore, orthotopic tumors from mice exposed to P. gingivalis exhibited tumor-infiltrating myeloid cell recruitment and a proinflammatory signature. P. gingivalis promoted CRC via NLRP3 inflammasome activation in vitro and in vivo. NLRP3 chimeric mice harboring orthotopic tumors showed that the effect of NLRP3 on P. gingivalis pathogenesis was mediated by hematopoietic sources. Collectively, these data suggest that P. gingivalis contributes to CRC neoplasia progression by activating the hematopoietic NLRP3 inflammasome.