Fig. 2

The proposed intricate nexus between the mouth and the gut during the gut inflammation: A microbial and immunological perspective. Bacteria-mediated pathway: certain oral pathobionts can be expanded in the inflamed oral cavity and reach the gut when colonization resistance given by gut commensals is perturbed. Upon entry of oral pathobionts into the intestine, they first penetrate the intestinal epithelium. Specific pathobionts can adhere to, and subsequently invade, epithelial cells. In the lamina propria, pathobionts can come across the immune cells such as macrophages, and activate inflammasome thereby fueling the gut inflammation via the release of proinflammatory cytokines (e.g., IL-1β). Host-cell mediated pathway: Concurrently with the direct migration of oral pathobionts to the gut as a result of co-existing oral and gut dysbiosis (as outlined in the above microbial pathway), the migration of oral immune cells to the gut is pivotal in the oral-gut axis during the pathogenesis of oral pathobiont-induced colitis. Mechanistically, during periodontal inflammation, Th17 cells primed orally can identify oral pathobionts (e.g., K. aerogenes) in the oral draining lymph nodes. These oral pathobiont-specific Th17 cells display gut-targeting molecules, including CCR9 and α4β7. Upon arrival in the gut, Th17 cells of oral origin can be stimulated by the translocated pathobionts, contributing to colitis. Given the phenotypic transition of oral Th17 cells to Th1 cells (evidenced in mice with periodontitis) and the simultaneous presence of the Th1-promoting factor IL-1β (produced by intestinal macrophages upon exposure to oral K. aerogenes, as shown in the above microbial pathway), it is plausible that both microbial and immunological pathways collectively exacerbate the intestinal pathology during oral pathobiont-driven gut inflammation