MPRO3 Regulates Macrophage Polarization and Osteoclastogenesis In Vitro and Attenuates Ligature-Induced Alveolar Bone Loss in Periodontitis.

Periodontal disease is a chronic inflammatory disorder characterized by the destruction of periodontal tissues. It is caused by microbial biofilm deposition and altered host immune responses. Prebiotics, probiotics, and postbiotics have recently gained attention as complementary therapeutic strategies against periodontal disease. Here, we investigated whether MPRO3, a formulation containing heat-killed Bifidobacterium animalis subsp. lactis, Lactiplantibacillus plantarum, and Lacticaseibacillus paracasei, could mitigate periodontal inflammation and bone resorption. Treatment of THP-1 cells with MPRO3 attenuated Porphyromonas gingivalis lipopolysaccharide-induced M1 polarization, while enhancing M2 polarization instead. In addition, MPRO3 suppressed osteoclast differentiation of bone marrow-derived macrophages and regulated the expression of osteoclastogenesis-related factors. In a mouse model of ligature-induced periodontitis, MPRO3 significantly attenuated alveolar bone loss, accompanied by decreased TRAP-positive osteoclasts, reduced RANKL expression, and lower systemic pro-inflammatory cytokine levels. Collectively, these findings indicate that MPRO3 regulates macrophage polarization and osteoclastogenesis, highlighting its potential as an adjunctive intervention in periodontal disease management.