The gut microbiome in oral health and disease: evidence toward bidirectional oral-gut axis communication.

The oral-gut microbiome axis has largely been seen as a unidirectional framework, in which dysbiotic oral flora is considered to contribute to gastrointestinal and systemic disease. However, recent evidence now challenges this view, indicating that gut microbial imbalance can act upstream to modulate oral immune homeostasis and disease susceptibility. Therefore, in the current perspective paper, we present a structured narrative review that synthesizes recent evidence from human microbiome, immunological, and genetic studies to propose a hypothetical mechanistic model in which gut dysbiosis may contribute to oral pathology. The literature discussed was identified through a targeted keyword-based search of major databases and complemented by manual screening of reference lists to capture relevant studies. Analyzing the evidence from human case-control and longitudinal cohort studies, as well as Mendelian randomization analysis, we identify convergent pathways linking gut dysbiosis to oral disease. These include systemic immune priming in autoimmune disorders with oral manifestations, depletion of gut-derived metabolites, such as short-chain fatty acids, that regulate epithelial barrier function and inflammation, and dysbiosis-associated barrier disruption that facilitates the systemic dissemination of microbial products and inflammatory mediators. Through these mechanisms, gut microbial imbalance contributes to chronic inflammatory conditions, altering host response and susceptibility to dental and mucosal diseases. In contrast, studies in healthy individuals show minimal oral-gut microbial overlap, supporting a model in which physiological compartmentalization is maintained in health and disrupted primarily under dysbiotic conditions. This synthesis reframes oral disease as host-microbiome dysregulation, highlighting gut microbiota as a driver of oral immune pathology.