Linking Periodontitis with Inflammatory Bowel Disease through the Oral-Gut Axis: The Potential Role of Porphyromonas gingivalis

Abstract

Periodontitis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases that are characterized by abnormal host immune responses and microbiota dysbiosis. Emerging evidence implies potential associations between periodontitis and IBD. Porphyromonas gingivalis (P. gingivalis), a primary cause of periodontitis, is thought to play a role in the development of IBD through the oral-gut disease axis. However, the precise mechanisms of its involvement remain enigmatic. In this narrative review, we begin with a discussion of the bidirectional relationship between periodontitis and IBD and the involvement of P. gingivalis in each of the two diseases. Further, we summarize the possible routes by which P. gingivalis links periodontitis and IBD through the oral-gut axis, as well as the underlying mechanisms of its involvement in the pathogenesis of IBD. Collectively, P. gingivalis participates in the progression of IBD through gut dysbiosis, impairment of the intestinal barrier, release of inflammatory mediators, and disturbance of the immune response. The above findings may provide new insights for exploring novel biomarkers and potential therapeutic approaches for IBD.

Keywords: Porphyromonas gingivalis; inflammatory bowel disease; oral–gut axis; periodontitis.

Figure 1

Mechanisms of P. gingivalis involvement in IBD (created with BioRender.com). (1) Gut dysbiosis: The reduced diversity of gut microbiota, accompanied by the increased ratio of Bacteroidetes to Firmicutes, leads to decreased production of SCFAs and inhibits the conversion of BAs. (2) Impairment of intestinal barrier: P. gingivalis decreases the expression level of the tight junction proteins ZO-1 and occludin, disrupting the epithelial barrier; meanwhile, gut dysbiosis contributes to the impairment of the intestinal barrier, increasing the invasion of conditioned pathogens. (3) Release of inflammatory mediators: P. gingivalis-derived LPS induces a semi-Th2-like response; in addition, P. gingivalis secretes gingipains that evade the intrinsic immune response by inhibiting DCs and causing the destruction of the intestinal barrier. (4) Disturbance of immune response: P. gingivalis induces the expression of proinflammatory cytokines; in addition, it upregulates the Th17/Treg ratio by regulating the transcription factors RoRγt and Foxp3. (SCFAs, short-chain fatty acids; BAs, bile acids; LPS, lipopolysaccharides; DCs, dendritic cells).