Gut and oral microbiota in oral bone tissue engineering: Impact of mechanistic and molecular pathways

The influence of the oral-gut microbiota on craniofacial bone healing is increasingly recognised, as its interactions with host osteoimmune pathways are now understood to shape the course of regeneration. These microbiota play an important role in maintaining bone mass via immune modulation, metabolite production, and nutrient resorption. Under conditions of dysbiosis, inflammatory signalling through NF-κB, NLRP3, and the RANKL/OPG axis is amplified, while Wnt/β-catenin and BMP/Smad pathways are suppressed, resulting in heightened oxidative stress, increased osteoclast activity, and progressive alveolar bone loss. In contrast, a balanced microbial community is associated with the production of short-chain fatty acids, through which epithelial barrier stability is supported, Th17/Treg equilibrium is restored, and osteoblast differentiation and mineralisation are promoted. In this review, mechanistic, preclinical, and emerging clinical evidence are integrated to illustrate how these microbial interactions regulate bone remodelling and influence the performance of engineered scaffolds. Therapeutic opportunities involving probiotics, prebiotics, synbiotics, engineered microbial strains, and microbiome-responsive biomaterials are emphasized. Cellular and molecular pathways controlling bone homeostasis, including the composition of the oral and gut microbiota, impacting oral bone health, have been summarized. Overall, the microbiome is positioned as a central biological determinant of oral bone regeneration, and its targeted modulation in addition to microbiome-based therapeutic strategies for bone tissue regeneration is proposed as a personalized approach for improving outcomes in craniofacial tissue engineering.