Invasive guests: the role of non-oral bacteria in oral dysbiosis and systemic health

Background The human oral cavity harbors a diverse microbiota essential for maintaining oral and systemic health. While most resident microorganisms are commensals adapted to specific oral niches, increasing evidence highlights the presence of non-oral bacteria, including Helicobacter pylori, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacteriaceae, Staphylococcus aureus, Acinetobacter baumannii, Enterococcus faecalis and Clostridioides difficile. Traditionally associated with other body sites, these bacteria may enter the oral cavity and, under favorable ecological conditions, persist through mechanisms such as biofilm formation, stress tolerance, entry into a viable but non-cultivable (VBNC) state, coaggregation with the oral microbiota, and evasion of host immune responses. Their colonization has been reported particularly in dysbiotic oral environments, including periodontitis and immunocompromised conditions, where overgrowth may also facilitate their recovery by conventional culture methods.Objective This review aims to summarize the current evidence on the presence, persistence mechanisms, clinical significance, and detection challenges of non-oral bacteria in the oral cavity, and to highlight the need for integrated diagnostic approaches.Design A comprehensive literature review was conducted focusing on studies reporting the isolation, detection, and clinical relevance of non-oral opportunistic bacteria in the oral cavity, with emphasis on culture-based and molecular diagnostic methods.Results Clinically, non-oral bacteria presence has been associated with dental caries, periodontal disease, endodontic infections, systemic dissemination, and their potential role as reservoirs of antibiotic resistance genes. Although several non-oral opportunistic bacteria can be readily isolated by culture when present at sufficient abundance, particularly in immunocompromised patients, detection may remain challenging in healthy individuals or low-biomass samples because of their transient or low-abundance occurrence, increasing the risk of misinterpretation.Conclusions Recognizing the oral cavity as a dynamic niche for non-oral bacteria underscores the need for integrated culture- and molecular-based diagnostic approaches, improved infection control strategies, and further research into their pathogenic potential.