Microbiome, alveolar bone, and metabolites: Connecting the dots

The oral microbiome (OM) is a diverse and dynamic collection of species, separated from alveolar bone by the oral mucosa. Pathogenic shifts in the OM (dysbiosis) during periodontitis are associated with an inflammatory response in the oral mucosa that drives alveolar bone resorption. Alveolar bone is also affected by metabolic disorders such as osteoporosis. Accumulating evidence has linked another microbial community, the gut microbiome (GM), to systemic bone metabolism and osteoporosis. Underlying this connection is the biologic activity of metabolites, byproducts of host and bacterial activity. Limited evidence also suggests that metabolites in the oral cavity signal between the OM and immune system, influencing both alveolar bone homeostasis and pathologic bone destruction in periodontitis. While the oral cavity and gut are connected through the gastrointestinal tract, dissimilar roles for known metabolites between these two niches exemplify the difficulty in translating knowledge on gut-derived metabolites and bone metabolism to alveolar bone. Integrated metabolomic, transcriptomic, and metagenomic approaches hold promise for resolving these challenges and identifying novel metabolites which impact alveolar bone health. Further interrogation through mechanistic testing in pre-clinical models and carefully controlled clinical studies have potential to lead toward translation of these discoveries into meaningful therapies.