<i>Porphyromonas gingivalis</i> Promotes Colorectal Carcinoma by Activating the Hematopoietic <i>NLRP3</i> Inflammasome

Abstract

<i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) is a keystone periodontal pathogen associated with various digestive cancers. However, whether <i>P. gingivalis</i> can promote colorectal cancer and the underlying mechanism associated with such promotion remains unclear. In this study, we found that <i>P. gingivalis</i> was enriched in human feces and tissue samples from patients with colorectal cancer compared with those from patients with colorectal adenoma or healthy subjects. Cohort studies demonstrated that <i>P. gingivalis</i> infection was associated with poor prognosis in colorectal cancer. <i>P. gingivalis</i> increased tumor counts and tumor volume in the <i>Apc^Min/+</i> mouse model and increased tumor growth in orthotopic rectal and subcutaneous carcinoma models. Furthermore, orthotopic tumors from mice exposed to <i>P. gingivalis</i> exhibited tumor-infiltrating myeloid cell recruitment and a proinflammatory signature. <i>P. gingivalis</i> promoted colorectal cancer via NLRP3 inflammasome activation <i>in vitro</i> and <i>in vivo</i>. NLRP3 chimeric mice harboring orthotopic tumors showed that the effect of NLRP3 on <i>P. gingivalis</i> pathogenesis was mediated by hematopoietic sources. Collectively, these data suggest that <i>P. gingivalis</i> contributes to colorectal cancer neoplasia progression by activating the hematopoietic NLRP3 inflammasome. SIGNIFICANCE: This study demonstrates that the periodontal pathogen <i>P. gingivalis</i> can promote colorectal tumorigenesis by recruiting myeloid cells and creating a proinflammatory tumor microenvironment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/10/2745/F1.large.jpg.