Oral Pathogens Meet the Gut Microbiome in Systemic Diseases: Key Pathogens and underlying Mechanisms

Guowu Gan^1,2Ruonan Chen¹Peining Zheng¹Kekao Long²Kenneth, King-yip CHENG^2*Jordy Evan Sulaiman^2*Xiaojing Huang^1*

• ¹School of Stomatology, Fujian Medical University, Fuzhou, China
• ²The Hong Kong Polytechnic University, Hong Kong, Hong Kong, SAR China

The oral-gut microbiome axis plays a pivotal role in systemic health, bridging oral microbial communities to distant organ systems through complex interactions involving microbial translocation, metabolic signaling, and immune modulation. Emerging evidence underscores the systemic impact of oral pathogens such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans, which disrupt gut microbiota balance, perturb metabolic regulation (short-chain fatty acids production and bile acid metabolism), compromise intestinal barrier integrity, and propagate inflammation across multiple tissues. Advances in multi-omics technologies and biomarker discovery could be utilized to develop oral-based diagnostic tools for early disease detection. Future research could elucidate inter-species interactions between oral pathogens and the gut microbiota, which could be harnessed to develop next-generation treatment strategies for intestinal dysbiosis and metabolic diseases. This includes the design of live bacterial therapeutics to inhibit oral pathogens in the oral cavity or the gut environment, thus mitigating microbiome-driven systemic diseases. Overall, this review highlights the critical need to integrate oral and gut microbiome research into holistic disease management frameworks, emphasizing the oral-gut axis as a frontier for understanding and treating chronic inflammatory and metabolic disorders.