Metagenomics in the Interplay Among Oral and Gut Dysbiosis.

Periodontitis is a chronic inflammatory disease increasingly recognized as a manifestation of complex microbial dysbiosis extending beyond the oral cavity. Recent advances in spatial metagenomics provide unprecedented resolution to investigate microbial community structure, function, and localization within periodontal niches and along the oral-gut axis. This review aims to explore how spatially resolved metagenomic approaches refine our understanding of the ecological and functional shifts in bacterial populations associated with periodontitis and their systemic implications. By integrating spatial mapping with shotgun metagenomics, we highlight distinct microenvironmental signatures within periodontal pockets, characterized by anaerobic pathobionts, metabolic reprogramming, and localized inflammatory gradients. Furthermore, we examine evidence supporting bidirectional interactions between oral and gut microbiota, suggesting that oral-derived taxa may contribute to gut dysbiosis through translocation and ecological disruption. From a basic science perspective, spatial metagenomics reveals niche-specific microbial functions and interspecies interactions that are not captured by bulk sequencing. Clinically, these insights open avenues for precision diagnostics and targeted therapeutics, including microbiome modulation strategies tailored to spatial microbial organization. Overall, this work underscores the importance of spatial context in metagenomic analyses and advances the conceptual framework linking periodontal disease to systemic microbial dysbiosis.