Oral‑gut axis in systemic disease: A barrier‑metabolism‑immunity three‑dimensional regulatory model (Review)

The oral‑gut axis is an interorgan regulatory network connecting the two core microbial niches in the human body. It sustains systemic homeostasis through bidirectional microbial translocation, metabolite signaling and immune crosstalk. The present review presented a novel barrier‑metabolism‑immunity three‑dimensional regulatory framework that clarifies the core mechanisms of oral‑gut axis dysregulation: Bidirectional translocation of oral and gut microbiota disrupts microbial homeostasis; key metabolites, including short‑chain fatty acids and trimethylamine N‑oxide, mediate interorgan signaling; immune cell migration and barrier damage collectively constitute the pathological basis, which drives multisystem disorders through secondary axes. The present study classified oral‑gut axis imbalance into three quantifiable subtypes: Barrier‑dominant, metabolism‑dominant and immunity‑dominant, each linked to distinct diseases such as inflammatory bowel disease, type 2 diabetes mellitus and rheumatoid arthritis. Accordingly, a stratified, personalized intervention strategy was proposed. Current challenges include difficulties in causal verification, substantial interindividual variability in intervention efficacy and limited tools for real‑time interorgan tracking. Future research will benefit from microbiota gene editing, multi‑omics integration and in vivo imaging to advance mechanistic understanding and clinical translation. This three‑dimensional model provides a standardized theoretical foundation and practical guidance for the diagnosis and treatment of oral‑gut axis‑related diseases.