The Gum-Gut Axis: Periodontitis and the Risk of Gastrointestinal Cancers

Simple Summary Periodontitis, a chronic inflammatory disease of the gums, and the oral microbiome have been recently implicated in the development of various cancers. Due to the mounting interest in the oro-intestinal axis, this review summarizes the current evidence linking periodontitis and oral bacteria to digestive tract cancers. The oral microbiome is a diverse ecosystem consisting of a variety of bacteria, some of which can move down to the gastrointestinal tract through enteral and hematogenous routes and contribute to multi-step carcinogenesis. Periodontitis and specific oral bacteria have been epidemiologically associated with an increased risk of esophageal, stomach, pancreatic, and colorectal cancers. The underlying mechanisms are still being investigated but may involve the production of carcinogenic metabolites by oral bacteria or immune evasion, as well as systemic inflammation triggered by periodontitis. These findings may have relevant implications for oral health and gastrointestinal cancer prevention, highlighting the importance of maintaining good oral hygiene and treating periodontitis.Abstract Periodontitis has been linked to an increased risk of various chronic non-communicable diseases, including gastrointestinal cancers. Indeed, dysbiosis of the oral microbiome and immune-inflammatory pathways related to periodontitis may impact the pathophysiology of the gastrointestinal tract and its accessory organs through the so-called "gum-gut axis". In addition to the hematogenous spread of periodontal pathogens and inflammatory cytokines, recent research suggests that oral pathobionts may translocate to the gastrointestinal tract through saliva, possibly impacting neoplastic processes in the gastrointestinal, liver, and pancreatic systems. The exact mechanisms by which oral pathogens contribute to the development of digestive tract cancers are not fully understood but may involve dysbiosis of the gut microbiome, chronic inflammation, and immune modulation/evasion, mainly through the interaction with T-helper and monocytic cells. Specifically, keystone periodontal pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum, are known to interact with the molecular hallmarks of gastrointestinal cancers, inducing genomic mutations, and promote a permissive immune microenvironment by impairing anti-tumor checkpoints. The evidence gathered here suggests a possible role of periodontitis and oral dysbiosis in the carcinogenesis of the enteral tract. The "gum-gut axis" may therefore represent a promising target for the development of strategies for the prevention and treatment of gastrointestinal cancers.